pregabalin and Pain

Use of the gabapentinoids for pain continues to increase. In 2018, the US Food and Drug Administration (FDA) strengthened the warnings for both gabapentin and pregabalin to emphasize the central nervous system side effects and the risk of respiratory depression, especially when combined with other centrally acting drugs. We reviewed the published comparative effectiveness literature for gabapentinoids for pain as well as all trials (published and unpublished) used by the FDA for the approval of the five pain indications for these agents (one for gabapentin, four for pregabalin). Among the findings of interest are the fact that the FDA rejected the application for gabapentin for diabetic peripheral neuropathy based on the risk versus benefit profile of that drug in the clinical trials that were submitted by the manufacturer. Additionally, both the comparative effectiveness trials as well as the studies used by the FDA tend to be short in duration and show only modest pain benefits for the gabapentinoids. The placebo response in these trials was frequently one-third to one-half as great as the pain benefit demonstrated by the gabapentinoid. Based on the available clinical trial evidence, we feel prescribers should be cautious when using gabapentinoids for pain, particularly when using these agents for a prolonged period or when combined with other, centrally acting agents.

Topics: Analgesics; Gabapentin; Humans; Pain; Pregabalin; United States; United States Food and Drug Administration

Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18 years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3 months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450 mg was superior to DLX 30 mg and PGB 150 mg, while DLX 20 mg and 30 mg were not superior to placebo. For the outcome R50%, AMT 25 mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450 mg was the best performance option for R30% and AMT 25 mg for R50%. PGB 150 mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison s

Topics: Adolescent; Adult; Amitriptyline; Child; Duloxetine Hydrochloride; Female; Fibromyalgia; Humans; Network Meta-Analysis; Pain; Pregabalin; Randomized Controlled Trials as Topic

Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation.  OBJECTIVES: Primary objective To determine if there is evidence of superiority of any particular pain relief regimen in the management of combination medical abortion (mifepristone + misoprostol) under 14 weeks' gestation (i.e. up to 13 + 6 weeks or 97 days). Secondary objectives To compare the rate of gastrointestinal side effects resulting from different methods of analgesia To compare the rate of complete abortion resulting from different methods of analgesia during medical abortion To determine if the induction-to-abortion interval is associated with different methods of analgesia To determine if any method of analgesia is associated with unscheduled contact with the care provider in relation to pain.. On 21 August 2019 we searched CENTRAL, MEDLINE, Embase, CINAHL, LILACs, PsycINFO, the World Health Organization International Clinical Trials Registry and ClinicalTrials.gov together with reference checking and handsearching of conference abstracts of relevant learned societies and professional organisations to identify further studies.. We included randomised controlled trials (RCTs) and observational studies (non-randomised studies of interventions (NRSIs)) of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation.. Two review authors (JRW and MA) independently assessed all identified papers for inclusion and risks of bias, resolving any discrepancies through discussion with a third and fourth author as required (CM and SC). Two review authors independently conducted data extraction, including calculations of pain relief scores, and checked for accuracy. We assessed the certainty of the evidence using the GRADE approach.. We included four RCTs and one NRSI. Due to the heterogeneity of study designs, interventions and outcome reporting, we were unable to perform meta-analysis for any of the primary or secondary outcomes in this review. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600 mg likely reduces the pain score when compared to a dose of paracetamol 2000 mg (mean difference (MD) 2.26 out of 10 lower, 95% confidence interval (CI) 3.00 to 1.52 lower; 1 RCT 108 women; moderate-certainty evidence). There may be little to no difference in pain score when comparing pregabalin 300 mg with placebo (MD 0.5 out of 10 lower, 95% CI 1.41 lower to 0.41 higher; 1 RCT, 107 women; low-certainty evidence).  There may be little to no difference in pain score when comparing ibuprofen 800 mg with placebo (MD 1.4 out of 10 lower, 95% CI 3.33 lower to 0.53 higher; 1 RCT, 61 women; low-certainty evidence). Ambulation or non-ambulation during medical abortion treatment may have little to no effect on pain score, but the evidence is very uncertain (MD 0.1 out of 5 higher, 95% CI 0.26 lower to 0.46 higher; 1 NRSI, 130 women; very low-certainty evidence). There may be little to no difference in pain score when comparing therapeutic versus prophylactic administration of ibuprofen 800 mg (MD 0.2 out of 10 higher, 95% CI 0.41 lower to 0.81 higher; 1 RCT, 228 women; low-certainty evidence).   Other outcomes of interest were reported inconsistently across studies. Where these outcomes were reported, there was no evidence of difference in incidence of gastrointestinal side effects, complete abortion rate, interval between misoprostol administration to pregnancy expulsion, unscheduled contact with a care provider, patient satisfaction with analgesia regimen nor patient satisfaction with abortion experience overall. However, the certainty of evidence was very low to low.. The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600 mg was shown to be effective, and it was less certain whether 800 mg was effective. Paracetamol 2000 mg does not improve pain scores as much as ibuprofen 1600 mg, however its use does not appear to cause greater frequency of side effects or reduce the success of the abortion. A single dose of pregabalin 300 mg does not affect pain scores during medical abortion, but like paracetamol, does not appear to cause harm. Ambulation or non-ambulation during the medical abortion procedure does not appear to affect pain scores, outcomes, or duration of treatment and so women can be advised to mobilise or not, as they wish. The majority of outcomes in this review had low- to very low-certainty evidence, primarily due to small sample sizes and two studies at high risk of bias. High-quality, large-scale RCT research is needed for pain management during medical abortion at gestations less than 14 weeks. Consistent recording of pain with a validated measure would be of value to the field going forward.

Topics: Abortion, Induced; Abortion, Spontaneous; Acetaminophen; Female; Humans; Ibuprofen; Mifepristone; Misoprostol; Pain; Pain Management; Pregabalin; Pregnancy

Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.. To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.. Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.. Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.. Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.. A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.. These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.

Topics: Amitriptyline; Duloxetine Hydrochloride; Fatigue; Female; Fibromyalgia; Humans; Male; Middle Aged; Milnacipran; Network Meta-Analysis; Pain; Pregabalin; United States; United States Food and Drug Administration

Systematic review.. This systematic review evaluates all randomized clinical trials (RCTs) conducted on assessing the efficacy and safety of pharmacologic therapies for the treatment of Spinal Cord Injury (SCI)-associated pain.. The PubMed/Medline, EMBASE, and Cochrane library online databases were searched from 1946 to May 2019 using specific search terms for SCI, pain, and RCTs meeting predetermined inclusion criteria. The efficacy outcome of interest was pain reduction, discontinuations, and adverse events (AEs).. Of 2746 records identified through database searching, 703 duplicates were deleted. 1814 were excluded, the full text of the remaining 230 articles was reviewed, and finally, 28 papers were selected for drafting. The most studied medications were pregabalin, gabapentin, amitriptyline, and ketamine. Pregabalin, gabapentin, and amitriptyline reduced VAS by more than 30%, and ketamine reduced VAS by 40%. Oxcarbazepine, lamotrigine, alfentanil, tramadol, and morphine added to clonidine, baclofen, and botulinum toxin type A (BTA) significantly reduced pain compared with placebo. On the other hand, valproate, levetiracetam, trazodone, and duloxetine did not significantly alleviate SCI-associated pain compared to placebo. The risks of AEs and discontinuations in anticonvulsants were the least, while it was highest in analgesics.. Studies of SCI-associated pain were few, small, heterogenic in measures and values, and did not allow quantitative comparisons of efficacy. However, available data suggested pregabalin and gabapentin led to a more marked reduction in SCI-associated pain with fewer AEs. Additional clinical studies are needed to assess the effect of established and novel management options.

Topics: Amitriptyline; Anticonvulsants; Gabapentin; Humans; Ketamine; Pain; Pregabalin; Spinal Cord Injuries

Chemotherapy-induced neuropathy is difficult to manage, and the pain associated with neuropathy is poorly responsive to gabapentin in a randomized trial. Duloxetine is the only drug that has been found to be effective in reducing pain from chemotherapy neuropathy. In this qualitative review, the use of pregabalin for chemotherapy-induced neuropathy is discussed including the rationale and pharmacological reasons why pregabalin should be considered in a large, randomized placebo-controlled trial.

Topics: Analgesics; Antineoplastic Agents; Duloxetine Hydrochloride; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin; Treatment Outcome

Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown.. The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis.. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs.. Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31;. Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

Topics: Anticonvulsants; Etanercept; Humans; Lamotrigine; Levetiracetam; Network Meta-Analysis; Pain; Pamidronate; Prednisone; Pregabalin

Neuropathy is the most common complication of diabetes. 50% of adults with diabetes will develop neuropathy in their lifetime. Diabetic peripheral neuropathy (DPN) is the major form of neuropathy found in 75% of diabetic neuropathy incidences. Pharmacological treatments are recommended for pain management in DPN. Anticonvulsants like pregabalin and gabapentin are the preferred first-line treatment, followed by amitriptyline, duloxetine, and venlafaxine. Topical agents like capsaicin and isosorbide dinitrate are also useful in treating the DPN and may be considered for the second or third-line treatment. Opioids and related drugs are suggested for short-term use during the acute exacerbation of pain. Combination therapy may be beneficial in patients who do not respond to monotherapy. However, currently, there is no compelling evidence to suggest any specific combination of agents. Disease-modifying agents such as alpha-lipoic acid and epalrestat appear to improve the disease state but are not recommended by any guideline. This review discusses the available pharmacological therapy for treating DPN. Also, we highlight the recommendations from different guidelines about the pharmacological treatment of DPN.

Topics: Anticonvulsants; Diabetes Mellitus; Diabetic Neuropathies; Humans; Pain; Pregabalin

The efficacy of monotherapy to reduce pain from diabetic peripheral neuropathy (DPN) is frequently not satisfactory and guidelines do not provide unanimous treatment options. In this context, multiple drug pharmacotherapy may provide benefit.. The aim of the present review is to describe the clinical trials addressing the pharmacotherapy of painful DPN. Studies discussing efficacy and tolerability of pharmacological agents that were assessed in monotherapy and in combination treatment are reported and discussed.. Several clinical trials have reported benefit of multiple-drug pharmacotherapy. Nevertheless, untoward effects of combination treatment are of concern. Importantly, some trials were restricted to comparison with placebo and other compared only with active comparator(s). Only limited clinical trials assessed selected cohorts of individuals experiencing different stages of painful DPN. Despite current limitations, some evidence of studies implicating a comparison to all active comparators points to safety and effectiveness of the combination of oxycodone with pregabalin and that of pregabalin with the 5% lidocaine plaster but future, clear-cut studies are required to drive evidence-based decisions in the clinical setting.

Topics: Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Humans; Pain; Pharmaceutical Preparations; Pregabalin

Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.

Topics: Analgesics; Animals; Humans; Pain; Pregabalin

Strong epidemiological and pathologic evidence associates NSAIDs with kidney disease, both acute and chronic. Hence, the usage of NSAIDs has decreased in patients with, or at risk for, chronic kidney disease (CKD). Coupled with this has been a rise in use of opioids and other non-NSAID alternatives, which do come with significant, and underrecognized, risk of nonrenal adverse events. We review the literature to understand if this shift is appropriate or deleterious.. NSAIDs do have a low but tangible risk in causing acute kidney injury, electrolyte imbalances, and increasing blood pressure. However, their role in causing progressive kidney disease is due to long-term usage in high cumulative dosages, and the use of NSAIDs in combination with other agents. Alternatives such as opioids, tramadol, gabapentin and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD.. Tradeoffs are inherent in using active pharmaceuticals, and NSAIDs are no exception. Balancing potential benefits with possible adverse effects around pain management should be a part of every conversation for patients with kidney disease.

Topics: Acute Kidney Injury; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Baclofen; Cost-Benefit Analysis; Gabapentin; Humans; Pain; Pregabalin; Renal Insufficiency, Chronic; Tramadol

This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to nervous tissue). Antiepileptic drugs have long been used in pain management. Pregabalin is an antiepileptic drug used in management of chronic pain conditions.. To assess the analgesic efficacy and adverse effects of pregabalin for chronic neuropathic pain in adults.. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from January 2009 to April 2018, online clinical trials registries, and reference lists.. We included randomised, double-blind trials of two weeks' duration or longer, comparing pregabalin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.. Two review authors independently extracted data and assessed trial quality and biases. Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale (moderate benefit); at least 50% pain intensity reduction; or very much improved on PGIC (substantial benefit). We calculated risk ratio (RR) and number needed to treat for an additional beneficial (NNTB) or harmful outcome (NNTH). We assessed the quality of the evidence using GRADE.. We included 45 studies lasting 2 to 16 weeks, with 11,906 participants - 68% from 31 new studies. Oral pregabalin doses of 150 mg, 300 mg, and 600 mg daily were compared with placebo. Postherpetic neuralgia, painful diabetic neuropathy, and mixed neuropathic pain predominated (85% of participants). High risk of bias was due mainly to small study size (nine studies), but many studies had unclear risk of bias, mainly due to incomplete outcome data, size, and allocation concealment.Postherpetic neuralgia: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (50% vs 25%; RR 2.1 (95% confidence interval (CI) 1.6 to 2.6); NNTB 3.9 (3.0 to 5.6); 3 studies, 589 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (32% vs 13%; RR 2.5 (95% CI 1.9 to 3.4); NNTB 5.3 (3.9 to 8.1); 4 studies, 713 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (62% vs 24%; RR 2.5 (95% CI 2.0 to 3.2); NNTB 2.7 (2.2 to 3.7); 3 studies, 537 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (41% vs 15%; RR 2.7 (95% CI 2.0 to 3.5); NNTB 3.9 (3.1 to 5.5); 4 studies, 732 participants, moderate-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 16% versus 5.5%, 600 mg 25% versus 5.8%; dizziness 300 mg 29% versus 8.1%, 600 mg 35% versus 8.8%.Painful diabetic neuropathy: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%; RR 1.1 (95% CI 1.01 to 1.2); NNTB 22 (12 to 200); 8 studies, 2320 participants, moderate-quality evidence), more had at least 50% pain intensity reduction (31% vs 24%; RR 1.3 (95% CI 1.2 to 1.5); NNTB 22 (12 to 200); 11 studies, 2931 participants, moderate-quality evidence), and more had PGIC much or very much improved (51% vs 30%; RR 1.8 (95% CI 1.5 to 2.0); NNTB 4.9 (3.8 to 6.9); 5 studies, 1050 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (63% vs 52%; RR 1.2 (95% CI 1.04 to 1.4); NNTB 9.6 (5.5 to 41); 2 studies, 611 participants, low-quality evidence), and more had at least 50% pain intensity reduction (41% vs 28%; RR 1.4 (95% CI 1.2 to 1.7); NNTB 7.8 (5.4 to 14); 5 studies, 1015 participants, low-quality e. Evidence shows efficacy of pregabalin in postherpetic neuralgia, painful diabetic neuralgia, and mixed or unclassified post-traumatic neuropathic pain, and absence of efficacy in HIV neuropathy; evidence of efficacy in central neuropathic pain is inadequate. Some people will derive substantial benefit with pregabalin; more will have moderate benefit, but many will have no benefit or will discontinue treatment. There were no substantial changes since the 2009 review.

Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Dizziness; Humans; Neuralgia; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleepiness

The gabapentinoid drugs gabapentin and pregabalin were originally developed as antiseizure drugs but now are prescribed mainly for treatment of pain. For gabapentin, the only pain-related indication approved by the US Food and Drug Administration (FDA) is postherpetic neuralgia. For pregabalin, FDA-approved indications related to pain are limited to postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy or spinal cord injury, and fibromyalgia. Despite these limited indications, gabapentin and pregabalin are widely prescribed off-label for various other pain syndromes. Such use is growing, possibly because clinicians are searching increasingly for alternatives to opioids.. This report summarizes the limited published evidence to support off-label gabapentinoid uses, describes clinical cases in which off-label use is problematic, and notes how review articles and guidelines tend to overstate gabapentinoid effectiveness.. Clinicians who prescribe gabapentinoids off-label for pain should be aware of the limited evidence and should acknowledge to patients that potential benefits are uncertain for most off-label uses.

Topics: Analgesics; Diabetic Neuropathies; Drug Approval; Fibromyalgia; Gabapentin; Humans; Low Back Pain; Minimal Clinically Important Difference; Neuralgia; Neuralgia, Postherpetic; Off-Label Use; Pain; Pain Measurement; Pregabalin; Radiculopathy; Sciatica; Spinal Cord Injuries

Gabapentinoids are frequently used in the management of cancer pain. In recent Cochrane systematic reviews, although there was an abundance of evidence relating to non-cancer pain, only a few studies related to cancer pain. This review summarizes recent randomised controlled trials (RCTs) evaluating the use of gabapentinoids for tumour-related (as monotherapy or part of combination therapy) and treatment-related pain.. For tumour-related pain, ten out of thirteen studies showed statistically significant benefits in favour of gabapentinoids. When used, as part of monotherapy or combination therapy, benefits were observed in five out of six studies evaluating gabapentin, and in six out of eight studies evaluating pregabalin. For treatment-related pain, none of the four studies (two gabapentin, two pregabalin) showed statistically significant benefits in favour of gabapentinoids. Unfortunately, many of the studies included were limited by small sample size, lack of blinding, and inadequate follow-up.. More and better quality studies are required, although it may be challenging to accomplish in this patient population. Gabapentinoids may offer benefits to cancer patients with pain, but careful titration and monitoring of adverse effects is necessary.

Topics: Analgesics; Analgesics, Opioid; Cancer Pain; Drug Therapy, Combination; Gabapentin; Humans; Pain; Pain, Postoperative; Palliative Care; Pregabalin; Radiotherapy; Randomized Controlled Trials as Topic; Severity of Illness Index

To evaluate pregabalin's efficacy (≤12 weeks) for pain relief and sleep improvement in patients with fibromyalgia (FM) and moderate-to-severe baseline pain.. Data were pooled from five randomized, double-blind, placebo-controlled, phase III clinical trials of pregabalin (300-450 mg/day) for FM treatment. Subjects, aged ≥18 years, had moderate (≥4-<7) or severe (≥7-10) mean baseline pain scores. Analyses included mixed effects repeated measures (MMRM), baseline observation carried forward (for parameters without enough data points for MMRM), or logistic regression.. Study number/ClinicalTrials.gov number: A0081056/NCT00645398, A0081077/NCT00230776, A0081100/NCT00333866, A0081208/NCT00830167.. Endpoints included mean change in pain and sleep quality scores (Weeks 8 and 12), patient-reported outcomes, and adverse events (AEs).. Baseline demographic characteristics were comparable between pregabalin and placebo in both baseline pain severity groups. Mean ± SD baseline pain severity scores were equivalent between pregabalin and placebo within moderate (5.8 ± 0.8) or severe pain (7.9 ± 0.7) subgroups. All subjects reported reduced pain and improved sleep quality through Weeks 8 and 12, with larger effects observed with pregabalin over placebo and with baseline severe over moderate pain (all p < 0.01). Pregabalin was generally well tolerated, AE findings were consistent with previously published trials, and AE profiles were similar between moderate and severe baseline pain subgroups. Limitations of this pooled analysis included differences in individual trial designs (e.g., dosing schedules, racial distribution, exclusion criteria that did not enroll mild severity patients).. Pregabalin was efficacious through 12 weeks for reducing pain and improving sleep quality in FM patients with baseline moderate or severe pain, with larger effects in the baseline severe pain subgroup. AEs were consistent with pregabalin's known safety profile and did not differ between moderate and severe pain subgroups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleep; Treatment Outcome; Young Adult

Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown.. We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity.. We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications.. Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting.

Topics: Analgesics; Humans; Pain; Pregabalin; Research Report

Pregabalin is an anticonvulsant drug that binds to the α₂δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.

Topics: Analgesics; Animals; Anticonvulsants; Calcium Channel Blockers; Calcium Channels; Central Nervous System; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment.

Topics: Diabetic Neuropathies; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin; Thiophenes

Hidradenitis Supprurativa is a painful dermatological condition. Although the pain of HS has unique aspects, the pain of HS pain shares common elements with essential pain, fibromyalgia, and pure neuropathic pain syndromes. Futhermore, depression plays an important role in the pain of HS. This paper reviews the potential for use of nonsteroidal anti-inflammatory drug (NSAIDS), acetaminophen, celecoxib, gabpentin, pregabalin, and the serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and venlafaxine, for treating HS related pain. No studies exist for pain control in HS. Initially, the pain of HS is treated medically e.g. oral rifampin and clindamycin or adalimumab to decrease inflammation, but an analysis of pain medications to treat the pain of HS merits its own discussion and treatment algorithm. First-line HS pain treatments include: topical analgesics and oral NSAIDs, such as celecoxib (Celebrex®), and acetaminophen. If these are inadequate, which is common, the less expensive gabapentin (Neurontin®) 400-1200 mg TID or the more expensive (Lyrica®) pregabalin 50-100mg BID can be added for synergistic effect. In my experience, HS patients prefer pregabalin, which induces less drowiness than gabapentin. If these combinations are inadequate, an SNRI can be added. Of SNRIs, duloxetine (Cymbalta®) 30-120 mg, given QD or divided BID, is most optimal. I have used gabapetin or pregabalin in combination with duloxtine effectively. Venlafaxine (Effexor®), 75 mg-375mg (divided into BID or TID dosing), or in extended release form Venlafaxine ER (Effexor ER®) (37.5mg-375mg daily) can be combined with pregalin or gabapetin. Venlafaxine's cardiovascular side effects and lesser effectiveness serves HS patients less well then duloxetine, in my experience. An advantage of duloxetine and venlafaxine is that they can be used to treat the depression often associated with HS. If prolonged use of opiates is required, patients should be referred to a pain specialist.

Topics: Acetaminophen; Amines; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclohexanecarboxylic Acids; Cyclohexanols; Drug Therapy, Combination; Duloxetine Hydrochloride; Gabapentin; gamma-Aminobutyric Acid; Hidradenitis Suppurativa; Humans; Pain; Pain Management; Pregabalin; Pyrazoles; Selective Serotonin Reuptake Inhibitors; Sulfonamides; Thiophenes; Venlafaxine Hydrochloride

Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately.. We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]).. Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results.. Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses.

Topics: Absenteeism; Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Cost of Illness; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life.. Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis.. Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose-response relationship was apparent for at least 50% pain relief and for adverse event outcomes.. Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.

Topics: Analgesics; Dose-Response Relationship, Drug; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Patient Satisfaction; Pregabalin; Randomized Controlled Trials as Topic; Statistics as Topic; Treatment Outcome

Central sensitization is one form of long-term plasticity in the central nervous system. Sustained activation of primary sensory fibers supplying dorsal horn can induce long-lasting increases in the discharge amplitude of primary afferent synapses. This is similar to the long-term potentiation that occurs in many other CNS regions. Drugs that limit the short-duration wind-up component of central sensitization include sodium channel blockers, NMDA antagonists, fast-acting opioids and the calcium-channel ligands gabapentin and pregabalin (S-3-(aminomethyl)-5-methylhexanoic acid). Pregabalin, like gabapentin, binds selectively to the Ca(V)α₂δ auxiliary subunit of presynaptic voltage-gated calcium channels. The conformational changes induced by this binding inhibit abnormally intense neuronal activity by reducing the synaptic release of glutamate and other neurotransmitters. Recent identification in animal models of increased Ca(V)α₂δ protein expression in chronic pain, allodynia, and hyperalgesia have drawn additional interest to drugs that bind the Ca(V)α₂δ site. Experimental studies with animal models and healthy human volunteers have shown that pregabalin reduces nociceptive responses, particularly in conditions involving central sensitization. Since these actions occur with relatively modest effects on physiological and cognitive functions, pregabalin may be an important consideration in the pharmacotherapy of otherwise difficult-to-treat pain syndromes.. This focus article discusses how the central nervous system plasticity phenomenon, central sensitization, is established in the induction and maintenance of chronic pain, allodynia, and hyperalgesia. In addition, it explores the neurophysiologic actions of the calcium-channel ligands gabapentin and pregabalin in limiting pathological manifestations of central sensitization.

Topics: Amines; Analgesics; Animals; Calcium Channels; Complex Regional Pain Syndromes; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Ligands; Neuronal Plasticity; Pain; Pregabalin

No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment.

Topics: Acetaminophen; Amines; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Gabapentin; gamma-Aminobutyric Acid; Humans; Morphine; Oxycodone; Pain; Pregabalin

To review the efficacy and safety of pregabalin, an alpha(2)-delta (alpha(2)-delta) ligand, for the management of fibromyalgia (FM).. Review of 2 pivotal phase 3 trials that evaluated the efficacy and safety of pregabalin for the management of FM.. FM is a chronic condition that is characterized by widespread musculoskeletal pain and has a greater prevalence in women than in men. In a 14-week, randomized, double-blind trial, pregabalin at all 3 doses (300, 450, and 600 mg daily) resulted in significantly greater improvements in pain and function relative to placebo. Parallel with these improvements, greater proportions of patients in the pregabalin groups reported improvement in global disease status compared with placebo. In a second study designed to evaluate the durability of response, patients were randomized to up to 6 months of treatment with pregabalin or placebo after a 6-week, open-label, dose-optimization treatment phase. Based on predefined criteria for loss of therapeutic response, patients treated with pregabalin were observed to maintain a therapeutic response for a significantly longer duration than patients treated with placebo. Pregabalin was tolerated by most patients in both trials; the incidence of the most commonly reported adverse events (dizziness, somnolence, weight gain, headache, dry mouth) appeared to be dose-related.. Pregabalin has been demonstrated to be efficacious and well-tolerated for the management of FM.

Topics: Analgesics; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Randomized Controlled Trials as Topic

Diabetic peripheral neuropathic pain affects the functionality, mood, and sleep patterns of approximately 10 to 20 percent of patients with diabetes mellitus. Treatment goals include restoring function and improving pain control. Patients can realistically expect a 30 to 50 percent reduction in discomfort with improved functionality. The main classes of agents used to treat diabetic peripheral neuropathic pain include tricyclic antidepressants, anticonvulsants, serotonin-norepinephrine reuptake inhibitors, opiates and opiate-like substances, and topical medications. Physicians should ask patients whether they have tried complementary and alternative medicine therapies for their pain. Only two medications are approved specifically for the treatment of diabetic peripheral neuropathic pain: pregabalin and duloxetine. However, evidence supports the use of other therapies, and unless there are contraindications, tricyclic antidepressants are the first-line treatment. Because patients often have multiple comorbidities, physicians must consider potential adverse effects and possible drug interactions before prescribing a medication.

Topics: Analgesics, Opioid; Anticonvulsants; Antidepressive Agents; Complementary Therapies; Diabetic Neuropathies; Drug Interactions; Drug Therapy, Combination; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Pregabalin; Recovery of Function; Thiophenes

Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed.. A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis.. Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited.. The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.

Topics: Amines; Analgesics, Non-Narcotic; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Female; Fibromyalgia; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Outcome Assessment, Health Care; Pain; Pregabalin; Randomized Controlled Trials as Topic; Treatment Outcome

Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator.. We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation.. Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences.. From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.

Topics: Amines; Analgesics; Analysis of Variance; Bayes Theorem; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Duloxetine Hydrochloride; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Peripheral Nervous System; Pregabalin; Randomized Controlled Trials as Topic; Thiophenes; Treatment Outcome

Chronic 'pathological' pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between 'normal' and 'pathological' pain transmission. Among these, pregabalin and gabapentin bind to the alpha(2)delta subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.

Topics: Amines; Analgesics, Non-Narcotic; Animals; Calcium Channels; Chronic Disease; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Guidelines as Topic; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin

What is the role of pregabalin (Lyrica) in the treatment of fibromyalgia? In this article the authors explore the putative pathophysiology of fibromyalgia, pregabalin's mechanism of action and evidence of efficacy, and its emerging role in treating this challenging disease.

Topics: Analgesics; Evidence-Based Medicine; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Palliative Care; Patient Satisfaction; Pregabalin; Severity of Illness Index; Sleep; Treatment Outcome

Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions.. To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain.. We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases.. Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome.. Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals.. There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above.. Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.

Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic

When presented with a chronic pain patient, a thorough diagnostic workup and clinical assessment are essential. A key component of this initial evaluation is to obtain the information necessary to identify the underlying cause of the pain. Although a definitive diagnosis is not always possible, pain is most effectively managed when the underlying cause is identified. Chronic pain is now viewed as a biopsychosocial phenomenon, in which biological, psychological, and social factors are at work. Although one or more chronic diseases may be responsible for at least some of the pain experienced by chronic pain patients, psychological factors also play a prominent role. According to several published reports, major depression occurs in up to 60% of chronic pain patients, and an adjustment disorder with anxious mood can be found in up to nearly a third. In addition, numerous studies have identified a high rate of substance abuse in those suffering from chronic pain, with lifetime prevalence rates ranging from 23% to 41%, according to one source. A pain history is another essential component of the initial workup. A thorough pain history includes questions on any previous therapies tried (including nonpharmacologic interventions) and the success rate of those therapies, an assessment of patient function and overall quality of life, and a review of any personal or family history of substance abuse. One of the complexities of pain diagnosis is the subjective nature of the condition. Simple validated measures, such as the 0 to 10 numerical scale, pictorial scales (eg, faces), and visual analog scales can assist in the assessment of pain intensity and the guidance of subsequent treatments. Of no less relevance in the initial workup of a patient with chronic pain is the establishment of a secure physician-patient relationship. Open and clear communication between these parties is a key component in the treatment process and will help guide the therapy more safely and efficaciously. Realistic expectations and exit strategies for each therapeutic intervention should also be discussed at the initial evaluation and again at the onset of treatment.

Topics: Administration, Cutaneous; Amines; Analgesics; Antidepressive Agents, Tricyclic; Carbamazepine; Chronic Disease; Clinical Protocols; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Monitoring; Drug Tolerance; Duloxetine Hydrochloride; Family Practice; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Lidocaine; Middle Aged; Pain; Practice Guidelines as Topic; Pregabalin; Randomized Controlled Trials as Topic; Substance-Related Disorders; Thiophenes; Treatment Outcome

Topics: Administration, Cutaneous; Amines; Analgesics; Analgesics, Opioid; Antidepressive Agents; Arthritis; Chemotherapy, Adjuvant; Chronic Disease; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Diagnosis, Differential; Gabapentin; gamma-Aminobutyric Acid; Humans; Lidocaine; Low Back Pain; Pain; Pain Measurement; Pain, Postoperative; Practice Guidelines as Topic; Pregabalin; Wounds and Injuries

Topics: Amines; Analgesics; Animals; Anticonvulsants; Calcium Channels; Carboxylic Acids; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Ligands; Mice; Mice, Mutant Strains; Pain; Peripheral Nervous System Diseases; Pregabalin; Prodrugs

Neuropathic pain encompasses a myriad of painful disease states that are often hard to treat, especially with one single medication. In the comprehensive treatment of neuropathic pain, the concept of complex polypharmacy is a rational approach, accompanied by physical and mental health therapies. Medications primarily used for neuropathic pain generally fall into the categories of anticonvulsants, antidepressants, opioids, and topical agents. Generally, most first-line medications used today show a response rate of approximately 30% to 50% reduction in pain in up to 50% of patients treated. There is no "gold standard" in regard to one medication for neuropathic pain. Some new medications have emerged during the past few years that help to augment the armamentarium of medications used in neuropathic pain. This paper reviews the definition of neuropathic pain and introduces the reader to the evidence-based literature on these new medications available for the treatment of neuropathic pain.

Topics: Analgesics; Animals; Cannabidiol; Chronic Disease; Dronabinol; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Guidelines as Topic; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin; Thiophenes

The pharmacologic management of fibromyalgia is based on the emerging evidence that pain in this disorder is primarily related to central pain sensitization. There is strong evidence that tricyclic antidepressants are effective, and moderate evidence for the effectiveness of serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors. Recent work suggests that the anti-seizure medications pregabalin and gabepentin are also effective. The only analgesic demonstrated to be helpful is tramadol.

Topics: Adrenergic Uptake Inhibitors; Amines; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents, Tricyclic; Cyclohexanecarboxylic Acids; Fibromyalgia; Gabapentin; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Selective Serotonin Reuptake Inhibitors; Tramadol; Treatment Outcome

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pregabalin are reviewed.. Pregabalin is the first drug to receive approved labeling from the Food and Drug Administration (FDA) for the treatment of painful diabetic neuropathy and postherpetic neuralgia and is the first antiepileptic agent to receive FDA-approved labeling since 1999. Pregabalin is the pharmacologically active S-enantiomer of racemic 3-isobutyl gamma-aminobutyric acid. Pregabalin has demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjunctive therapy for adult patients with partial onset seizures. Its exact mechanism of action is unknown. Pregabalin is rapidly absorbed and exhibits linear pharmacokinetics after oral administration. The lack of hepatic metabolism and lack of interaction with cytochrome P-450 isoenzymes explain the absence of drug interactions with pregabalin. Several clinical studies have demonstrated pregabalin's efficacy for each of the FDA-approved indications, with dizziness and somnolence reported as the most common adverse events. Pregabalin has been designated as a Schedule V controlled substance because of its potential for abuse and dependence. The starting dosage for patients with neuropathic pain associated with diabetic peripheral neuropathy is 50 mg three times daily and may be increased to 300 mg daily within one week based on efficacy and tolerability. The starting dosage for patients with partial-onset seizures is 75 mg twice daily or 50 mg three times daily and may be increased to 600 mg daily based on individual response and tolerability.. Pregabalin may be beneficial for the treatment of neuropathic pain or partial-onset seizures in patients who do not respond to conventional treatments or cannot tolerate their adverse effects.

Topics: Animals; Anticonvulsants; Diabetic Neuropathies; Epilepsy, Partial, Sensory; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Chronic, neuropathic pain may be secondary to myriad etiologies including diabetic peripheral neuropathy and fibromyalgia. It is a debilitating condition that imposes a significant burden on individuals and society alike. This article will review various instruments designed to assess quality of life (QoL) and key data assessing QoL of patients suffering from these diseases as well as currently available pharmacologic agents for symptomatic management. As basic and clinical science progress over the next few years, along with the introduction of novel pharmacologic agents, we anticipate greater potential for pain intervention and improvement in the quality of life of our patients.

Topics: Antidepressive Agents; Diabetic Neuropathies; Duloxetine Hydrochloride; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Quality of Life; Randomized Controlled Trials as Topic; Thiophenes

New treatment options for diabetic peripheral neuropathic pain (DPNP) have recently been developed, including two Food and Drug Administration (FDA) approved agents, duloxetine and pregabalin. As clinicians face a broader spectrum of efficacious treatments, side-effect profiles play an increasingly important role in the development of a pain management regimen. In this article we review the safety profile of agents commonly used in the treatment of DPNP.

Topics: Administration, Topical; Analgesics; Anesthetics, Local; Anticonvulsants; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Capsaicin; Cyclohexanols; Diabetic Neuropathies; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Thiophenes; Venlafaxine Hydrochloride

Pregabalin is increasingly being used for the treatment ofneuropathic pain, often as the first-line choice. The question is, however, whether this choice is based on evidence. Seven trials have been published on the effect ofpregabalin in patients with postherpetic neuralgia and painful diabetic neuropathy. These trials more frequently report a 50% reduction in pain in pregabalin treated patients than in patients treated with placebo (number needed to treat 4.3). Dizziness and somnolence are the most frequent adverse events of pregabalin. The number needed to harm for adverse events leading to discontinuation of treatment varies from 3.7 to 113.1 in these studies. Pregabalin has not been compared head-to-head with other drugs commonly used for neuropathic pain. Indirect comparison reveals the effectiveness of pregabalin is comparable with that of carbamazepin, tramadol, and gabapentin; pregabalin is possibly less effective than amitriptylin. However, taking into account its price and the lack of clinical experience and evidence, using pregabalin as first-line choice is not recommended.

Topics: Analgesics; Cost-Benefit Analysis; Diabetic Neuropathies; Evidence-Based Medicine; gamma-Aminobutyric Acid; Humans; Neuralgia, Postherpetic; Pain; Pregabalin; Treatment Outcome

Gabapentin and pregabalin bind to the alpha-2-delta calcium channel subunit and represent a novel analgesic drug class. The evidence base supporting their use for chronic neuropathic and early postsurgical pain is reviewed.. Multiple, large, high-quality trials have demonstrated the safety and efficacy of gabapentin and pregabalin in neuropathic pain. Treatment-related improvement of pain and sleep positively impact upon quality of life. Sedation, dizziness and ataxia are important and relatively common adverse effects, however. Accumulating evidence indicates that gabapentin, and possibly pregabalin, also exert important effects following surgery. Multiple high-quality trials have demonstrated analgesic and opioid-sparing efficacy with gabapentin following various surgical procedures. Gabapentin and pregabalin reduce movement-evoked pain and this can lead to enhanced functional postoperative recovery. Postoperative opioid sparing is of questionable relevance since few trials have shown reduced opioid-related adverse effects. Sedation, dizziness and ataxia have been reported in only a few trials. Future larger-scale perioperative trials focused on safety assessment are needed, however.. Gabapentin and pregabalin are efficacious treatments for neuropathic and postsurgical pain. Future research addressing several specific questions would serve to better delineate their optimal roles in treating these and other pain conditions.

Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Female; Forecasting; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Neuralgia; Pain; Pain, Postoperative; Pregabalin

Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid. It is an alpha2-delta (alpha2-delta) ligand that has analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. Pregabalin binds potently to the alpha2-delta subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and substance P. In this review, I will discuss the pharmacology of pregabalin and available efficacy studies in pain management. This review will focus on the advances in pregabalin pharmacology since my previous review in 2005.

Topics: Animals; Disease Management; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Synthesized in 1990 as an anticonvulsant agent, pregabalin was designed as a lipophilic gamma-aminobutyric acid (GABA) analog substituted at the 3'-position in order to facilitate diffusion across the blood-brain barrier. It is an alpha2delta1 ligand that binds to, and modulates, voltage-gated calcium channels. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurologic and psychotic disorders. Pregabalin has analgetic, anticonvulsant, and anxiolytic activity and has demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy for adult patients with partial onset seizures. Pregabalin was significantly more effective than placebo for the treatment of generalized anxiety disorder as well as of fibromyalgia and was well tolerated by most of the patients.

Topics: Analgesics; Anxiety Disorders; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and accompanied by a variety of other symptoms such as fatigue, sleep dysfunction, depression, anxiety and cognitive disturbance. Current guidelines recommend tricyclic antidepressants or SSRIs (selective serotonin reuptake inhibitors) as first-line therapies to treat the multiple symptom domains. Until recently, however, there were no licensing authority approved treatments for FMS. The alfa 2 delta modulator pregabalin has anxiolytic, anticonvulsant and antinociceptive properties which has prompted its investigation in FMS. In a series of short-term randomized, double-blind, placebo-controlled trials of 8-14 weeks duration, pregabalin proved effective in reducing the pain and accompanying symptoms of FMS and improved quality of life domains. A 6-month double-blind, placebo-controlled trial demonstrated the durability of its effects on pain and a variety of secondary measures such as fatigue and sleep disturbance. Overall, pregabalin was well tolerated with no new adverse events emerging that have not been reported with its use in other indications.

Topics: Anticonvulsants; Anxiety Disorders; Cognition Disorders; Depression; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Quality of Life; Sleep Wake Disorders; Syndrome

Neuropathic pain is a condition affecting a significant proportion of the world's population. Many therapeutic drugs have been used. They achieve less than satisfactory results and are associated to common side effects that affect the daily life of patients. Pregabalin is a new drug that has been shown to be effective for treating partial epilepsy and peripheral neuropathic pain in clinical trials. It is a structural, but not functional, analogue of GABA. It acts as a ligand of the alpha2-delta subunit, a protein associated to the voltage-dependent calcium channels. Modulation of these channels decreases calcium entry into nerve endings, resulting in a decreased release of several excitatory neurotransmitters. Pregabalin had a linear pharmacokinetics with little variability between the different subjects. It does not bind to plasma proteins, has no liver metabolism, and is excreted trough the kidneys. Few interactions with other drugs may be expected based on these characteristics. In clinical trials, pregabalin has been shown to be effective in postherpetic neuralgia and painful diabetic neuropathy at doses ranging from 150-600 mg/day. The analgesic effects of pregabalin occur in the first few days of treatment and are sustained over time. Side effects are few; most are transient and well-tolerated by patients, and the treatment discontinuation rate is minimal.

Topics: Analgesics; Animals; Clinical Trials as Topic; Diabetic Neuropathies; gamma-Aminobutyric Acid; Humans; Neuralgia, Postherpetic; Pain; Pregabalin

Pregabalin, a compound with a novel mechanism of action (MOA), has demonstrated efficacy as an adjunctive treatment for epilepsy and in several neuropathic pain models. Multiple generalized anxiety disorder (GAD) clinical trials have shown that pregabalin has efficacy similar to the benzodiazepines and venlafaxine. Onset of anxiolytic effect was observed as early as Week 1 of treatment, and efficacy was seen in treating both psychic and somatic anxiety symptoms. Pregabalin binds potently and selectively to the alpha-2-delta subunit of "hyper-excited" voltage-gated calcium channels (VGCCs). The binding of pregabalin to VGCCs changes their conformation, reducing calcium influx at nerve terminals. Pregabalin only modulates the release of excitatory neurotransmitters in "hyper-excited" neurons, restoring them to normal physiological state. This newly defined MOA is believed to confer on pregabalin its anxiolytic, analgesic, and anticonvulsant properties. Thus, pregabalin may offer physicians an effective and well-tolerated therapy for GAD, which differs from existing treatments.

Topics: Agoraphobia; Animals; Anti-Anxiety Agents; Clinical Trials as Topic; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Pregabalin (Lyrica, Pfizer) is a GABA analog with similar structure and actions to gabapentin. It has antiepileptic, analgesic and anxiolytic activity. Pregabalin is indicated for the management of neuropathic pain associated with diabetic neuropathy and post-herpetic neuralgia. Peak plasma levels occur approximately 1 hour after oral doses and oral bioavailability is about 90%. Based on AUC data, food does not significantly affect the extent of absorption. Pregabalin is not protein-bound and exhibits a plasma half-life of about 6 hours, which is not dose-dependent. Hepatic metabolism is negligible, and most of the oral dose (95%) appears unchanged in the urine. Pregabalin is a safe and well-tolerated new treatment for neuropathic pain. Furthermore, pregabalin has proven efficacy in adjunctive therapy of refractory partial seizures and in the treatment of acute pain, generalized anxiety disorder and social phobia.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Anxiety Agents; Anticonvulsants; Diabetic Neuropathies; Fibromyalgia; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Neuralgia; Pain; Pregabalin

To review pregabalin's pharmacology, pharmacokinetics, efficacy, and adverse effects in the treatment of neuropathic pain, epilepsy, and anxiety.. A MEDLINE search (1993-October 2005) for peer-reviewed English-language publications was performed. Abstracts from professional meetings were also included. Key terms were anxiety, diabetic neuropathy, epilepsy, neuropathic pain, postherpetic neuralgia, pregabalin, and seizures.. Basic pharmacology data were extracted from animal studies; pharmacokinetic data were extracted from human studies. Multicenter, double-blind, placebo-controlled, parallel-group studies were included to describe the efficacy and adverse effects of pregabalin.. Pregabalin is a new agent that exerts its pharmacodynamic effect by modulating voltage-gated calcium channels. Pregabalin has a linear pharmacokinetic profile. It is completely absorbed, not bound to plasma proteins, not metabolized, and eliminated unchanged through the kidneys. Doses must be adjusted in patients with renal insufficiency. Clinical trials showed that pregabalin is effective in neuropathic pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, in partial epilepsy as adjunctive therapy, and in generalized and social anxiety disorders. The most common adverse effects were dizziness and somnolence. Few serious adverse effects were reported. Pregabalin should not be discontinued rapidly.. Pregabalin is an effective and safe analgesic, antiepileptic, and anxiolytic medicine. It will provide a new treatment option for patients with neuropathic pain and partial epilepsy.

Topics: Agoraphobia; Anxiety; Diabetic Neuropathies; Epilepsy; gamma-Aminobutyric Acid; Herpesviridae Infections; Humans; Multicenter Studies as Topic; Neuralgia; Neurotransmitter Agents; Pain; Peripheral Nervous System Diseases; Pregabalin; Randomized Controlled Trials as Topic; Seizures

This article reviews the available information on pregabalin, a new anticonvulsant for peripheral neuropathic pain. Pregabalin was provisionally approved by the US Food and Drug Administration in December 2004 and was granted final approval after controlled substance scheduling (Schedule V) by the US Drug Enforcement Agency in August 2005.. A MEDLINE search (1986-August 2005) was conducted to identify pertinent studies in the English language. The search terms included pregabalin, PD144723, CI-1008, gabapentin, and neuropathic pain. Additional references were obtained from the bibliographies of identified articles. All studies that evaluated any aspect of pregabalin in vitro or in vivo in animals or humans were included, with a focus on data relevant to older adults.. In preclinical studies, pregabalin, a structural congener of gabapentin, exhibited antinociceptive activity in animal models of neuropathic and inflammatory pain. Unlike gabapentin, pregabalin was well absorbed (> 90%), and its absorption was dose independent. Like gabapentin, pregabalin was predominantly excreted unchanged in the urine (> or = 98%). Dosed at 50 to 200 mg TID, pregabalin was superior to placebo in relieving pain and improving sleep and health-related quality of life in patients with diabetic peripheral neuropathy and postherpetic neuralgia (P < 0.001-P < 0.049). No active-controlled trials were available. The most problematic adverse events associated with pregabalin were dizziness and somnolence (21%-26%).. In the absence of active-controlled clinical trials and geriatric-specific efficacy/tolerability data, the place of pregabalin in the analgesic armamentarium for the elderly is unclear. Because pregabalin is a Schedule V controlled substance, its utility is not compromised by substantial limitation of access or the need for extra steps in prescribing. However, abuse potential is a consideration, and utilization should be carefully monitored, particularly in patients with a past or current history of substance abuse. The improved pharmacokinetic profile of pregabalin relative to gabapentin is manifested in linear and dose-independent absorption and a narrow therapeutic dosing range. However, pregabalin still requires multiple administrations per day, and daily doses > 150 mg/d require dose titration. The relatively high frequency of central nervous system adverse events, particularly dizziness and somnolence, is a concern in the elderly. Time and further experience should clarify the role of this agent.

Topics: Aged; Amines; Analgesics, Non-Narcotic; Anticonvulsants; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Interactions; Gabapentin; gamma-Aminobutyric Acid; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin

Pregabalin is a gamma-aminobutyric acid analog that is under development by Pfizer for the potential treatment of central nervous system disorders, including epilepsy, neuropathic pain, fibromyalgia and generalized anxiety disorder. By April 2003, Pfizer had filed for approval of pregabalin in Europe for neuropathic pain and as an adjunctive therapy for epilepsy, and in October 2003 an NDA was filed for these indications and generalized anxiety disorder. At this time, phase III trials in fibromyalgia were ongoing.

Topics: Analgesics, Non-Narcotic; Animals; Anticonvulsants; Anxiety Disorders; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Seizures; Structure-Activity Relationship

Pfizer is developing pregabalin, a follow-up compound to its GABA agonist gabapentin, for the potential treatment of several central nervous system (CNS) disorders including epilepsy, neuropathic pain, anxiety and social phobia [286425]. By December 2000, Pfizer anticipated filing an NDA for pregabalin for seven major indications (beginning with neuropathic pain and add-on epilepsy), with the FDA by the end of 2001. Filings for generalized anxiety disorder (GAD), social anxiety disorder and fibromyalgia are expected to take place in 2002, and filings for epilepsy monotherapy and panic disorders are expected to take place in early- and late-2003, respectively [336918], [393182], [399956]. By January 2001, pregabalin was in phase II development in Japan for the potential treatment of neuropathic pain, with an anticipated approval date of 2005 [394827]. However, following analysis by the FDA of a mouse study that showed incidence of a specific tumor type, Pfizer announced in February 2001, that it is restricting the use of pregablin in some clinical patients [398726] and it has frozen trials for neuropathic pain [398785]. In April 2001, Morgan Stanley Dean Witter predicted potential sales of $350 million in 2002, rising to $1750 million in 2006, with peak sales in excess of $2000 million [406923].

Topics: Agoraphobia; Animals; Anticonvulsants; Clinical Trials as Topic; Contraindications; GABA Agonists; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Structure-Activity Relationship

The purpose of the present study (a randomized clinical trial) was to evaluate the preemptive analgesic effects of pregabalin combined with celecoxib in total knee arthroplasty (TKA).. From January 2019 to June 2021, we enrolled 149 patients who underwent TKA and divided them into four groups: the placebo group (. The pain scores upon movement were significantly lower in the combination group than in the other three groups at 6, 12, 24, and 48 hours after surgery (. The preemptive analgesia regimen of pregabalin combined with celecoxib had positive effects on improving acute pain and reducing the cumulative dose of opioids after TKA. This trial is registered with ChiCTR2100041595.

Topics: Analgesia; Analgesics, Opioid; Arthroplasty, Replacement, Knee; C-Reactive Protein; Celecoxib; Double-Blind Method; Humans; Pain; Pain, Postoperative; Pregabalin; Prospective Studies; Sufentanil

Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. Participants received maximally tolerated doses of ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome was daily pain (0-10); secondary outcomes included Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. The primary outcome of daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was not significantly different ( P = 0.54). There were no significant differences between combination and each monotherapy for any secondary outcomes, although combination and pregabalin were both superior to ALA for measures of mood and sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.

Topics: Analgesics; Double-Blind Method; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Thioctic Acid; Treatment Outcome

Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics. The aim of this study was to evaluate the efficacy of supplementing ongoing pregabalin (PGB) and duloxetine (DLX) treatment with palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) for 24 weeks in FM patients.. After undergoing three months of stable treatment with DLX+PGB, FM patients were randomised to continue the same treatment (Group 1) or to add PEA 600 mg b.i.d + ALC 500 mg b.i.d. (Group 2) for a further 12 weeks. Every two weeks throughout the study, cumulative disease severity was estimated using the Widespread Pain Index (WPI) as the primary outcome measure; the secondary outcomes were the fortnightly scores of the patient-completed revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FASmod) questionnaire. All three measures were expressed as time-integrated area under the curve (AUC) values.. One hundred and thirty (91.5%) of the initial 142 FM patients completed the study: 68 patients in Group 1 and 62 in Group 2. Twenty-four weeks after randomisation, the Group 2 patients showed additional significant improvements in all three outcome measures. Although there was some fluctuation in both groups during the study period, the AUC values of the WPI scores steadily decreased in Group 2 (p=0.048), which also showed better outcomes in terms of the AUC values of the FIQR (p=0.033) and FASmod scores (p=0.017).. This is the first randomised controlled study demonstrating the effectiveness of the adding on therapy of PEA+ALC to DLX+PGB in FM patients.

Topics: Acetylcarnitine; Analgesics; Duloxetine Hydrochloride; Fibromyalgia; Humans; Pain; Pregabalin; Treatment Outcome

Few new drugs have been developed for chronic pain. Drug development is challenged by uncertainty about whether the drug engages the human target sufficiently to have a meaningful pharmacodynamic effect. IMI2-PainCare-BioPain-RCT1 is one of four similarly designed studies that aim to link different functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics. This study focusses on biomarkers derived from nerve excitability testing (NET) using threshold tracking of the peripheral nervous system.. This is a multisite single-dose, subject and assessor-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD), and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from NET of large sensory and motor fibers and small sensory fibers using perception threshold tracking will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose with at least 1 week apart. Motor and sensory NET will be assessed on the right wrist in a non-sensitized normal condition while perception threshold tracking will be performed bilaterally on both non-sensitized and sensitized forearm skin. Cutaneous high-frequency electrical stimulation is used to induce hyperalgesia. Blood samples will be taken for pharmacokinetic purposes and pain ratings as well as predictive psychological traits will be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split across the two primary outcomes: strength-duration time constant (SDTC; a measure of passive membrane properties and nodal persistent Na. Measurements of NET using threshold tracking protocols are sensitive to membrane potential at the site of stimulation. Sets of useful indices of axonal excitability collectively may provide insights into the mechanisms responsible for membrane polarization, ion channel function, and activity of ionic pumps during the process of impulse conduction. IMI2-PainCare-BioPain-RCT1 hypothesizes that NET can serve as biomarkers of target engagement of analgesic drugs in this compartment of the nociceptive system for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification.. This trial was registered 25/06/2019 in EudraCT ( 2019-000942-36 ).

Topics: Biomarkers; Double-Blind Method; Healthy Volunteers; Humans; Lacosamide; Multicenter Studies as Topic; Pain; Peripheral Nerves; Pregabalin; Randomized Controlled Trials as Topic; Tapentadol

Peripheral neuropathies commonly affect quality of life of patients due to pain, sleep disturbances, and fatigue, although trials have not adequately explored these domains of care. The aim of this study was to assess the impact of nortriptyline, duloxetine, pregabalin, and mexiletine on pain, sleep, and fatigue in patients diagnosed with cryptogenic sensory polyneuropathy (CSPN).. We implemented a Bayesian adaptive design to perform a 12-wk multisite, randomized, prospective, open-label comparative effectiveness study in 402 CSPN patients. Participants received either nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). At prespecified analysis timepoints, secondary outcomes, Patient Reported Outcomes Measurement Information System (PROMIS) surveys including Short Form (SF)-12, pain interference, fatigue, and sleep disturbance, were collected.. Mexiletine had the highest quit rate (58%) due to gastrointestinal side effects, while nortriptyline (38%) and duloxetine (38%) had the lowest quit rates. If tolerated for the full 12 wk of the study, mexiletine had the highest probability (>90%) of positive outcomes for improvements in pain interference and fatigue. There was no significant difference among the medications for sleep disturbance or SF-12 scores. Adverse events and lack of efficacy were the two most common reasons for cessation of therapy.. Physicians caring for patients with CSPN should consider mexiletine to address pain and fatigue, although nortriptyline and duloxetine are better medications to trial first since they are better tolerated. Future research should compare other commonly used medications for CSPN to determine evidence-based treatment strategies.

Topics: Activities of Daily Living; Bayes Theorem; Diabetic Neuropathies; Double-Blind Method; Duloxetine Hydrochloride; Fatigue; Humans; Mexiletine; Nortriptyline; Pain; Pregabalin; Prospective Studies; Quality of Life; Sleep; Treatment Outcome

IMI2-PainCare-BioPain-RCT2 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on specific compartments of the nociceptive system that could serve to accelerate the future development of analgesics. IMI2-PainCare-BioPain-RCT2 will focus on human spinal cord and brainstem activity using biomarkers derived from non-invasive neurophysiological measurements.. This is a multisite, single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Neurophysiological biomarkers of spinal and brainstem activity (the RIII flexion reflex, the N13 component of somatosensory evoked potentials (SEP) and the R2 component of the blink reflex) will be recorded before and at three distinct time points after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol), and placebo, given as a single oral dose in separate study periods. Medication effects on neurophysiological measures will be assessed in a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin), and in a non-sensitized normal condition. Patient-reported outcome measures (pain ratings and predictive psychological traits) will also be collected; and blood samples will be taken for pharmacokinetic modelling. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between the two primary endpoints, namely the percentage amplitude changes of the RIII area and N13 amplitude under tapentadol. Remaining treatment arm effects on RIII, N13 and R2 recovery cycle are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modelling are exploratory.. The RIII component of the flexion reflex is a pure nociceptive spinal reflex widely used for investigating pain processing at the spinal level. It is sensitive to different experimental pain models and to the antinociceptive activity of drugs. The N13 is mediated by large myelinated non-nociceptive fibers and reflects segmental postsynaptic response of wide dynamic range dorsal horn neurons at the level of cervical spinal cord, and it could be therefore sensitive to the action of drugs specifically targeting the dorsal horn. The R2 reflex is mediated by large myelinated non-nociceptive fibers, its circuit consists of a polysynaptic chain lying in the reticular formation of the pons and medulla. The recovery cycle of R2 is widely used for assessing brainstem excitability. For these reasons, IMI2-PainCare-BioPain-RCT2 hypothesizes that spinal and brainstem neurophysiological measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification.. This trial was registered on 02 February 2019 in EudraCT ( 2019-000755-14 ).

Topics: Analgesics; Biomarkers; Brain Stem; Cross-Over Studies; Double-Blind Method; Healthy Volunteers; Humans; Lacosamide; Multicenter Studies as Topic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Spinal Cord; Tapentadol

We hypothesized that the addition of coenzyme Q10 (CoQ10) to pregabalin might be helpful in improving symptoms in patients suffering from painful diabetic neuropathy (PDN).. One hundred twelve patients with PDN were randomly allocated to receive CoQ10 + pregabalin (57 patients) or placebo + pregabalin (55 patients). Besides pregabalin (150 mg/day), the patients, upon their group assignment, received CoQ10 at a dosage of 100 mg every 8 h or matched placebo for 8 consecutive weeks. The primary efficacy measure was the changes in the pain intensity from baseline to endpoint measured on an 11-point NRS (numeric rating scale). Secondary efficacy measures included the changes in the pain-associated sleep interference score (SIS) as well as the patients' global improvement with treatment measured on the Clinicians' and Patients' Global Impression of Change (CGIC/PGIC).. On the intent‑to‑treat population (ITT) analysis, the CoQ10 + pregabalin regimen resulted in significantly greater pain relief than the placebo + pregabalin regimen. By the end of week 2, the decrease in the mean pain NRS score was similar in both groups, but at the end of weeks four and eight, the decrease in the mean pain NRS score was significantly greater in patients taking CoQ10 + pregabalin than in those taking placebo + pregabalin (p value = 0.01 and < 0.001, respectively). Likewise, at the end of week 8, the decrease in the pain-associated SIS was significantly greater in the patients supplemented with CoQ10 compared to placebo. Furthermore, the proportion of the responder patients (those having ≥ 50% decline in the mean pain NRS score) as well as the proportion of patients rated ''very much'' or ''much improved'' on the CGIC/PGIC scales were also significantly higher in the CoQ10 + pregabalin-treated patients than placebo + pregabalin-treated patients.. Our data support the idea that diabetic patients suffering from PDN may benefit from using antioxidant and anti-inflammatory supplements like CoQ10. However, further studies are required before supplementation with CoQ10 can be recommended for treating PDN.. The trial was registered at Iranian Registry of Clinical Trials (identifier code: IRCT20120215009014N385). Registration date: 2021-02-21.

Topics: Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Double-Blind Method; gamma-Aminobutyric Acid; Humans; Iran; Pain; Pregabalin; Treatment Outcome; Ubiquinone

The social pain or invalidation denoting painful feeling following social conflicts or misunderstanding about illness legitimacy has been proposed as a salient disabling symptom besides physical pain or non-pain symptoms in fibromyalgia (FM). We sought to evaluate the effect of 1-month administration of duloxetine or pregabalin on the invalidation dimensions in FM patients with respect to the comparison of these two drugs on this issue.. This open-label randomized clinical trial study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Primary outcome measure (Illness Invalidation Inventory (3*I)) and secondary outcome measures (Beck Depression Inventory-II (BDI-II), widespread pain index (WPI), and polysymptomatic distress scale (PSD)) were compared before and after treatment, using paired t test or Wilcoxon signed test.. Of 81 eligible FM patients, 44 patients in the duloxetine arm and 27 patients in the pregabalin arm completed the study protocol. Overall, no significant improvement was seen in 3*I scores after treatment with either duloxetine or pregabalin, except in the lack of understanding of medical professionals which improved after treatment with pregabalin (2.43 ± 1.38 to 1.79 ± 0.94, p value: 0.01). There were no intragroup and intergroup differences in the effects of duloxetine and pregabalin on 3*I scores when adjusted with the cofounders. Both duloxetine and pregabalin improved WPI, BDI-II, and PSD scores significantly.. Short-term FM pharmacological treatment had no effect on social pain. This finding was regardless of drug type, improvement of physical pain, and depression.

Topics: Analgesics; Duloxetine Hydrochloride; Fibromyalgia; Humans; Pain; Pharmaceutical Preparations; Pregabalin; Treatment Outcome

Currently, central neuromodulators are among the therapeutic options for the treatment of functional dyspepsia (FD). Pregabalin, a gabapentinoid, is a neuromodulator that could potentially improve visceral hypersensitivity in FD patients.. To assess the efficacy and safety of pregabalin for the treatment of FD METHODS: We performed a randomised placebo-controlled study including FD patients who did not respond to proton pump inhibitors. Patients were randomly assigned to receive pregabalin (75 mg daily) or placebo for 8 weeks. The primary outcome was an adequate relief response rate. The secondary outcomes were improvement in quality of life, pain scores in divided categories, and safety profile.. Of 72 patients enrolled, 34 received pregabalin and 38 received placebo. The self-reported adequate relief rates in the pregabalin and placebo groups were 70.6% and 42.1% at week 4 (P = 0.02), and 70.6% and 44.7% at week 8 (P = 0.03), respectively. The reduction in global symptoms in the pregabalin and placebo groups were 11.7 ± 10.6 and 3.7 ± 8.9 points at week 4 (P < 0.01) and 15.1 ± 12.2 and 8.0 ± 10.2 points at week 8 (P = 0.01), respectively. Pregabalin improved the overall quality of life (P = 0.03). The most common adverse event with pregabalin was dizziness, occurring in 51.6% of patients.. Pregabalin led to significant alleviation of dyspeptic symptoms, especially in patients with predominant epigastric pain . Thaiclinicaltrials.org #TCTR20200404002.

Topics: Double-Blind Method; Dyspepsia; Humans; Pain; Pregabalin; Proton Pump Inhibitors; Quality of Life; Treatment Outcome

In patients with chronic pancreatitis (CP), pain relief is a dilemma. Antioxidants with pregabalin therapy have been reported to be useful. Hence, this study was carried out to determine the efficacy of the combination of antioxidant and pregabalin therapy in reducing pain in patients with CP.. This was a prospective, double blind, superiority, and randomized trial in patients with CP. The treatment group received pregabalin with antioxidants therapy for 8 weeks, and a similar placebo was administered to the controls. Primary outcome was to determine the change in maximum pain intensity assessed by visual analog scale (VAS) and Izbicki pain score. Secondary outcomes were the number of painful days, opioid and non-opioid requirements, improvement in quality of life, number of hospital admission, and overall patient satisfaction.. A total of 90 patients were randomized to 45 in each arm. Demographic profile and baseline pain score were comparable. Patients in treatment group when compared to placebo group had a significant reduction in pain intensity (VAS score 2 ± 0.8 vs. 1.3 ± 0.9; p = 0.007), non-opioid analgesic requirement in days (54.4±2.9 vs. 55.7±1.5; p = 0.014), and number of hospital admissions (0.2 ± 0.5 vs. 0.6 ± 0.7; p = 0.002), respectively. Significant proportion of patients was satisfied in the treatment group compared to placebo group (18% vs. 11%; p = 0.03).. The combination of pregabalin and antioxidant significantly reduces the pain, requirement of non-opioid analgesics, and the number of hospital admissions in patients with CP. It also significantly improves the overall patient satisfaction.. CTRI/2017/05/008492.

Topics: Analgesics; Antioxidants; Double-Blind Method; Drug Therapy, Combination; Humans; Pain; Pancreatitis, Chronic; Pregabalin

IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity.. This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory.. LEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification.. This trial was registered 25/06/2019 in EudraCT ( 2019%2D%2D001204-37 ).

Topics: Biomarkers; Cross-Over Studies; Double-Blind Method; Electroencephalography; Healthy Volunteers; Humans; Lacosamide; Pain; Pain Measurement; Pregabalin; Tapentadol

To apply the sequential up-down method to a human experimental pain model in order to examine the opioid-sparing effect of oral pregabalin on intravenous alfentanil.. Double-blind, randomized, crossover.. Academic university medical center.. Thirty-one healthy males.. The median effective plasma concentration of intravenous alfentanil was determined under two conditions: alfentanil alone (phase I) and alfentanil+ pregabalin (300 mg orally) (phase II). The alfentanil plasma level (after a computer-controlled infusion) producing a success criterion (at least 30% intradermal capsaicin-induced pain reduction compared with placebo) was used to determine higher or lower doses for each sequential subject. The median dose producing a success criterion and its confidence interval were determined.. On the basis of the t test for a difference across phase and regression coefficients across groups, there was no opioid-sparing effect of pregabalin on alfentanil. Four subjects in phase I and five subjects in phase II did not complete the study. Two in phase I were technical failures, with the rest in both phases stopped because of side effects. Of the subjects who completed the study, six of 19 subjects in phase I and 11 of 12 subjects in phase II reported side effects.. When the intradermal capsaicin-induced pain model was used in healthy volunteers, oral pregabalin had no opioid-sparing effects on intravenous alfentanil. This experimental model may be useful in studying analgesic interactions.

Topics: Alfentanil; Analgesics, Opioid; Capsaicin; Double-Blind Method; Humans; Hyperalgesia; Male; Pain; Pregabalin

Persistent and, in particular, neuropathic pain is a major healthcare problem with still insufficient pharmacological treatment options. This triggered research activities aimed at finding analgesics with a novel mechanism of action. Results of these efforts will need to pass through the phases of drug development, in which experimental human pain models are established components e.g. implemented as chemical hyperalgesia induced by capsaicin. We aimed at ranking the various readouts of a human capsaicin-based pain model with respect to the most relevant information about the effects of a potential reference analgesic. In a placebo-controlled, randomized cross-over study, seven different pain-related readouts were acquired in 16 healthy individuals before and after oral administration of 300 mg pregabalin. The sizes of the effect on pain induced by intradermal injection of capsaicin were quantified by calculating Cohen's d. While in four of the seven pain-related parameters, pregabalin provided a small effect judged by values of Cohen's d exceeding 0.2, an item categorization technique implemented as computed ABC analysis identified the pain intensities in the area of secondary hyperalgesia and of allodynia as the most suitable parameters to quantify the analgesic effects of pregabalin. Results of this study provide further support for the ability of the intradermal capsaicin pain model to show analgesic effects of pregabalin. Results can serve as a basis for the designs of studies where the inclusion of this particular pain model and pregabalin is planned.

Topics: Administration, Oral; Adolescent; Adult; Analgesics; Capsaicin; Cross-Over Studies; Humans; Hyperalgesia; Injections, Intradermal; Male; Pain; Pain Measurement; Pregabalin; Young Adult

Sodium channel blockers are used for the treatment of pain, but this is limited by the lack of selectivity for different sodium channel subtypes, which can result in central nervous system and cardiovascular side effects. As such, there is special interest in the Na

Topics: Adolescent; Adult; Analgesics; Cross-Over Studies; Double-Blind Method; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged; NAV1.7 Voltage-Gated Sodium Channel; Nociception; Pain; Pain Measurement; Phenyl Ethers; Pregabalin; Sodium Channel Blockers; Sulfonamides; Treatment Failure; Young Adult

The primary objective of the study was to evaluate the efficacy of 300 milligrams (mg) and 600 mg of pregabalin compared to placebo in the reduction of pain in patients with noncritical partial and full thickness burn injuries.. A prospective, randomized, double-blinded, single center, placebo-controlled trial was conducted. Simple randomization method was used in this trial. After subjects met all the inclusion and none of the exclusion criteria, they were randomized and assigned to 1 of the 3 18-day treatments groups: Pregabalin 300 group, Pregabalin 600 group, or Placebo group. Demographics and clinical characteristics were recorded. The severity of pain was assessed by using the visual analog scale for pain intensity at baseline on day 3, day 9 ± 3, day 25 ± 7, day 90 ± 6, and day 180 ± 12.. A total of 54 subjects were randomly assigned, and 51 were included in the data analysis. Demographics and clinical characteristics did not differ significantly between the 3 groups. There was a statistically significant difference in pain between the Pregabalin 300 and Pregabalin 600 groups (P-value = .0260). The Pregabalin 300 group had 17.93 units (95% confidence interval: 1.83-34.04) higher pain scores on average than the Pregabalin 600 group, regardless of time. The adjusted P-value comparing 0 to 300 was .1618, while the adjusted P-value for 0 versus 600 was .5304. There was an overall difference in pain across time regardless of study group (P-value = <.0001). An overall difference in opioid consumption (P-value = .0003) and BSHS (P-value = .0013) across time regardless of study group was noted.. Pregabalin could be part of a promising multimodal analgesic regimen in noncritical burn population. Future placebo-controlled studies assessing the use of pregabalin in burn victim patients may further endorse our findings.

Topics: Adult; Analgesics; Analgesics, Opioid; Burns; Combined Modality Therapy; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebos; Pregabalin; Prospective Studies; Treatment Outcome; Visual Analog Scale

Although coenzyme Q10 (CoQ10) supplementation has shown to reduce pain levels in chronic pain, the effects of CoQ10 supplementation on pain, anxiety, brain activity, mitochondrial oxidative stress, antioxidants, and inflammation in pregabalin-treated fibromyalgia (FM) patients have not clearly elucidated. We hypothesised that CoQ10 supplementation reduced pain better than pregabalin alone

Topics: Adult; Brain; Double-Blind Method; Female; Fibromyalgia; Humans; Inflammation; Leukocytes, Mononuclear; Male; Middle Aged; Mitochondria; Oxidative Stress; Pain; Positron-Emission Tomography; Pregabalin; Ubiquinone

To evaluate whether prophylactic pregabalin reduces pain experienced with medication abortion.. We conducted a randomized, double-blind, placebo-controlled trial of women initiating medication abortion with mifepristone and buccal misoprostol up to 70 days of gestation. Participants were randomized to 300 mg oral pregabalin or a placebo immediately before misoprostol. The primary outcome was maximum pain on an 11-point numerical rating scale, reported using real-time electronic surveys over 72 hours. Secondary outcomes included pain at each time point, ibuprofen and narcotic use, side effects, and satisfaction. We estimated that 110 women would be required to have 80% power to detect a difference in pain of 1.3 points.. Between June 2015 and October 2016, 241 women were screened and 110 were randomized (56 pregabalin, 54 placebo). Three were lost to follow-up. The primary outcome of mean maximum pain in the pregabalin group was 5.0±2.6 vs 5.5±2.2 in the placebo group (P=.32). Excluding medication taken before the study capsule, ibuprofen was used by 64% (35/55) of the pregabalin group vs 87% (45/52) placebo (P<.01). Narcotics were used by 29% (16/55) of the pregabalin group vs 50% (26/52) placebo (P<.03). More dizziness (P<.001), sleepiness (P<.04), and blurred vision (P<.05) occurred in the pregabalin group. Satisfaction scores for the analgesic regimen were higher in the pregabalin group (very satisfied: 47% vs 22%; P=.006).. Compared with placebo, 300 mg pregabalin coadministered with misoprostol during medication abortion did not significantly decrease maximum pain scores. Women who received pregabalin were less likely to require any ibuprofen or narcotic and were more likely to report higher satisfaction with analgesia, despite an increase in dizziness, sleepiness, and blurred vision.. ClinicalTrials.gov, NCT02782169.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Adult; Analgesics; Female; Humans; Misoprostol; Pain; Pregabalin; Pregnancy; Young Adult

Sickle cell disease (SCD) pain may have a neuropathic component. Adjuvant drugs used to treat neuropathic pain have not been studied for the treatment of adults with SCD. To determine the safety and feasibility of using pregabalin for chronic SCD pain. A randomized, controlled, double-blind pilot study. Based on random assignment, participants were treated with pregabalin or placebo control for 3 months with monthly follow-up visits. Participants were recruited from the University of Illinois Hospital and Health Sciences System outpatient SCD clinic. Participants/Subjects: A total of 22 participants with SCD (21 African American, 1 other) were included 16 women aged 18-82 (mean age 33.1 ± 9.9). PAINReportIt, Leeds Assessment of Neuropathic Signs and Symptoms, Neuropathic Pain Symptom Inventory, and Short Form 36 Health Survey were completed. Adverse effects were minimal. Mean scores for average pain intensity, composite pain index, and neuropathic pain revealed a reduction for pregabalin and placebo control groups. Although the between-group differences were not significant, sustained reduction in pain over time within the pregabalin group indicated promising effects of pregabalin for SCD pain. Mean quality-of-life scores increased slightly over time (representing better quality of life) in 7 of 8 domains for the pregabalin group and decreased in 4 of 8 domains for the placebo control group. Small sample size made it difficult to interpret quality-of-life findings. This pilot study provided sufficient evidence that further investigation of pregabalin's potential efficacy for treatment of chronic SCD pain in adults is warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Anemia, Sickle Cell; Chronic Pain; Double-Blind Method; Female; Humans; Illinois; Male; Middle Aged; Pain; Pain Management; Pilot Projects; Pregabalin

Topics: Analgesics; Double-Blind Method; Humans; Middle Aged; Pain; Pain Measurement; Pregabalin; Sciatica

Neuropathic pain is the most severe and resistant type of pain which has impact on quality of life and behaviour; it most commonly occurs at night causing disturbed sleep. Diabetes mellitus is a common cause of painful neuropathy. In this study, we are comparing the effectiveness of old treatment Carbamazepine with Pregabalin in painful diabetic neuropathy. The study was an open-label trial conducted in Diabetic Clinic of Medical Unit-III, Jinnah Post-graduate Medical Center, Karachi. The duration of the study was 90 days, from December 2010 to March 2011. The study has been approved from ethical committee of JPMC, Karachi with the reference NO.F.2-81/2010-GENL/195/JPMC. 60 established patients of painful diabetic peripheral neuropathy from Diabetic Clinic of Medical Unit-III OPD were included in the 90-day study, irrespective of gender, with duration of diabetes more than 10 years. All subjects are placed into two groups. In group A, comprising of 30 patients (n=30), Pregabalin was administered and in group B, also comprising of 30 patients (n=30), Carbamazepine. The intensity of pain was compared on visual analog scale of McGill pain questionnaire. In group A (Pregabalin), the mean pain score fell from 6.17±0.14 to 3.50±0.15 from day 0 to day 90 (p-value=0.001) and the percentage of change also in visual analog scale of McGill pain questionnaire was -43.31%. In group B (Carbamazepine), the changes in pain score from initially 6.07±0.14 falling to 4.23±0.13 from day 0 to day 90 (p-value=0.001) and the percentage of change was -30.31%. Pregabalin was observed to be more potent. Both drugs were well tolerated by all participants that also completed the entire duration of the trial.

Topics: Analgesics, Non-Narcotic; Carbamazepine; Diabetic Neuropathies; Female; Humans; Male; Medical Records; Middle Aged; Pain; Pain Measurement; Peripheral Nervous System Diseases; Pregabalin; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM.. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups.. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p < 0.0001) but not in the placebo group (p = 0.56) (difference in correlation coefficients between groups; p = 0.004). Furthermore, the initial CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R. The analgesic effect of pregabalin depends on the original endogenous analgesia status. Its effect on conditioned pain modulation (CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia.

Topics: Adult; Analgesia; Analgesics; Double-Blind Method; Female; Humans; Male; Pain; Pain Management; Pain Measurement; Pregabalin; Young Adult

To investigate baseline demographics and disease characteristics as predictors of the analgesic effect of duloxetine and pregabalin on diabetic peripheral neuropathic pain (DPNP).. Based on data from the COMBO-DN study, a multinational clinical trial in DPNP, the potential impact of baseline characteristics on pain relief after 8-week monotherapy with 60 mg/day duloxetine or 300 mg/day pregabalin was assessed using analyses of covariance. Subgroups of interest were characterized regarding their baseline characteristics and efficacy outcomes.. A total of 804 patients were evaluated at baseline. A significant interaction with treatment was observed in the mood symptom subgroups with a larger pain reduction in duloxetine-treated patients having no mood symptoms [Hospital Anxiety and Depression Scale (HADS) depression or anxiety subscale score <11; -2.33 (duloxetine); -1.52 (pregabalin); p = 0.024]. There were no significant interactions between treatment for subgroups by age (<65 or ≥65 years), gender, baseline pain severity [Brief Pain Inventory Modified Short Form (BPI-MSF) average pain <6 or ≥6], diabetic neuropathy duration (≤2 or >2 years), baseline haemoglobin A1c (HbA1c) (<8% or ≥8%), presence of comorbidities and concomitant medication use.. Our analyses suggest that the efficacy of duloxetine and pregabalin for initial 8-week treatment in DPNP was consistent across examined subgroups based on demographics and disease characteristics at baseline except for the presence of mood symptoms. Duloxetine treatment appeared to be particularly beneficial in DPNP patients having no mood symptoms.

Topics: Affect; Age Factors; Aged; Analgesics; Anticonvulsants; Antidepressive Agents; Anxiety; Depression; Diabetic Neuropathies; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Pain; Pregabalin; Psychiatric Status Rating Scales; Treatment Outcome

The authors investigated if timing of medical treatment is associated with the analgesic effect of pregabalin or placebo in patients with chronic pancreatitis (CP).. Sixty-four patients received pregabalin (150-300 mg twice a day) or matching placebo for 3 consecutive weeks. Responders to treatment were defined as patients with a reduction in clinical pain scores of 30% or greater. Factors associated with timing of pain treatment (ie, duration of CP and opioid usage) were collected at baseline. In addition, other factors that potentially could influence outcome (eg, clinical pain scores prior to study medication, diabetes, and exocrine pancreatic insufficiency) were also included. Conventional groupwise logistic regression and analysis on the individual patient level with a machine learning technique were used to predict treatment response.. In the conventional statistical analysis duration of CP (odds ratio, 0.9; 95% confidence interval, 0.8-1.1; P = 0.3) and opioid treatment (odds ratio, 1.0; 95% confidence interval, 0.9-1.1; P = 0.6) were not associated with pain relief. In addition, none of the supplementary factors were associated with treatment response (all P > 0.1). Likewise, in the individual patient-level analysis, none of the included variables reached classification accuracies greater than chance level (all P > 0.1).. Pregabalin can be added as adjuvant analgesic at any time point during the disease course of CP.

Topics: Adult; Aged; Analgesics; Double-Blind Method; Drug Administration Schedule; Humans; Logistic Models; Male; Middle Aged; Pain; Pain Measurement; Pancreatitis, Chronic; Placebos; Pregabalin; Risk Factors; Time Factors; Treatment Outcome

Pregabalin is widely used perioperatively. The authors explored the effects of pregabalin, remifentanil, and their combination on experimental pain, ventilatory, and cognitive function.. In a randomized, double-blinded crossover study, 12 volunteers received (1) pregabalin + placebo, (2) placebo + remifentanil, (3) pregabalin + remifentanil, and (4) placebo + placebo. Pregabalin 150 mg/placebo was administered twice orally. After baseline, remifentanil/placebo was given as effect-site target-controlled infusion (TCI): 0.6, 1.2, and 2.4 ng/ml. Pain during cold pressor test was scored on visual analog scale (0 to 100 mm). Ventilation was measured by spirometry and cognition tested with Color-Word Interference and Rapid Information Processing tests.. Pain intensity after placebo was (mean) 72 mm (95% CI, 62 to 83). Pregabalin reduced pain score by -10 mm (-14 to -7, P < 0.001). Remifentanil had dose-dependent analgesic effect, reducing pain score by -47 mm (-54 to -39, P < 0.001) on highest TCI level, whereas pregabalin + remifentanil exerted additive effect, reducing pain score by -57 mm (-64 to -50, P < 0.001). Respiratory depression was potentiated by adding pregabalin to remifentanil; end-tidal carbon dioxide was 39.3 mmHg (37.2 to 41.3) with placebo, increased 1.8 mmHg (-0.9 to 4.6, P = 0.4) with pregabalin, 10.1 mmHg (4.9 to 15.4, P < 0.001) with remifentanil, and 16.4 mmHg (11.3 to 21.5, P < 0.001) with pregabalin + remifentanil on highest TCI level. The combination pregabalin + remifentanil, but not either drug alone, adversely affected all cognitive tests.. The combination of pregabalin and remifentanil had additive analgesic effects, pregabalin potentiated remifentanil ventilatory depression, and the combination adversely affected cognition. These results question the clinical benefit of the combination compared with higher doses of opioids.

Topics: Adult; Analgesics; Cognition; Cross-Over Studies; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Male; Pain; Piperidines; Pregabalin; Remifentanil; Respiration; Respiratory Function Tests; Young Adult

This randomized, double-blind, placebo-controlled, crossover trial evaluated the pharmacodynamic effects of a single 100-mg dose of ABT-639, a peripherally active, selective T-type Ca. Healthy adult males (aged 21 to 55 years) were randomly assigned to receive single oral doses of ABT-639, pregabalin, and placebo.. Serial measurements for area (cm. Nineteen participants were randomized and included in the analysis. No significant differences were observed between ABT-639 and placebo in spontaneous pain, elicited pain, and areas of allodynia, hyperalgesia, and flare after intradermal capsaicin injection at 1 and 4 hours post-dose. In contrast, pregabalin demonstrated significant reductions in spontaneous pain at 1 and 4 hours post-dose, and elicited pain and areas of allodynia and hyperalgesia at 4 hours post-dose compared with placebo. ABT-639 demonstrated acceptable safety and tolerability; somnolence and euphoric mood were the most commonly reported adverse events.. These data indicate that a single 100-mg dose of ABT-639 had no effect on experimental pain induced by intradermal capsaicin injection.

Topics: Adult; Calcium Channel Blockers; Calcium Channels, T-Type; Capsaicin; Cross-Over Studies; Double-Blind Method; Heterocyclic Compounds, 2-Ring; Humans; Injections, Intradermal; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Sulfonamides; Young Adult

Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN.. Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment.. Both drugs showed reduction of pain intensity, without significant statistical difference (P = 0.900). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P = 0.014.. Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298.

Topics: Adolescent; Adult; Aged; Amines; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Drug Combinations; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Thiamine; Visual Analog Scale; Vitamin B 12

The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis.. In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated.. We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol.. Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis.

Topics: Adult; Analgesics, Non-Narcotic; Antioxidants; Calculi; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Pain; Pain Measurement; Pancreatitis, Chronic; Pregabalin; Quality of Life; Recurrence; Secondary Prevention; Treatment Outcome; Young Adult

Fibromyalgia (FM) is a chronic pain disorder with patients frequently suffering from comorbid conditions, including osteoarthritis (OA). Data on how FM patients with comorbid OA respond to recommended therapies (such as pregabalin) could help their treatment.. This was a pooled exploratory analysis of three randomized placebo-controlled clinical trials of pregabalin in FM patients to assess the impact of comorbid OA on the response to pregabalin.. Patients were divided into those with and without comorbid OA. Difference in change in least squares (LS) mean pain score at endpoint (assessed by 0-10 numeric rating scale, controlled for baseline pain score) with pregabalin (300 mg/day and 450 mg/day) vs placebo was assessed. Changes in Patient Global Impression of Change (PGIC) responders and Fibromyalgia Impact Questionnaire (FIQ) total score were also assessed.. There were 1665 patients in the analysis set (558, placebo; 552, pregabalin 300 mg/day; 555, pregabalin 450 mg/day), including 296 with comorbid OA. Pregabalin 450 mg/day significantly improved the LS mean (95% confidence interval) difference in pain score vs placebo in patients with (0.99 [0.44, 1.55], P < 0.001), and without (0.64 [0.39, 0.89], P < 0.001) OA. Improvements with pregabalin 300 mg/day with (0.31 [-0.25, 0.86], P = 0.276) and without (0.51 [0.25, 0.76], P < 0.001) OA were not consistently significant. Improvements in PGIC and FIQ total score were observed in patients with and without comorbid OA.. FM patients with or without comorbid OA respond to treatment with pregabalin 450mg/day with significant improvements in pain intensity scores. These data could provide guidance to healthcare professionals treating these patients.

Topics: Adolescent; Adult; Aged; Analgesics; Comorbidity; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Pregabalin; Treatment Outcome; Young Adult

Pregabalin has been used for the treatment of pain. A clinically accepted method applied to patients with pain has not been published for the determination of pregabalin in human plasma. This study developed a fluorometric ultrahigh-performance liquid chromatography (UHPLC) method to measure pregabalin concentration in patients with pain.. After plasma pretreatment involving protein precipitation, pregabalin and gabapentin as an internal standard were derivatized with 4-fluoro-7-nitrobenzofurazan (NBD-F) under the following reaction conditions: 1 minute, pH 10, and 60°C. The UHPLC separation was performed using a 2.3-μm particle size octadecylsilyl column. The fluorescence detector was set at excitation and emission wavelengths of 470 and 530 nm, respectively. The predose blood samples were collected from 40 patients with pain who have been treated with 75 mg of pregabalin twice daily.. The chromatographic run time was 1.25 minutes. No interfering peaks were observed in the blank plasma at the retention times of NBD derivatives. The calibration curve of pregabalin was linear at a range of 0.05-10 mcg/mL (r > 0.999). The lower limit of quantification was 0.05 mcg/mL. The intra-assay accuracy and precision were 98.3%-99.8% and within 4.3%, respectively. The inter-assay accuracy and precision were 103.2%-107.1% and within 4.1%, respectively. The predose plasma concentration of pregabalin in patients with pain ranged from 0.14 to 8.5 mcg/mL.. This study provides a validated fluorometric UHPLC method with fast analytical performance for the determination of pregabalin in human plasma. The present method could be applied to patients with pain and be used for the clinical research or therapeutic drug monitoring of pregabalin.

Topics: Amines; Analgesics; Chromatography, High Pressure Liquid; Cyclohexanecarboxylic Acids; Data Accuracy; Fluorometry; Gabapentin; gamma-Aminobutyric Acid; Humans; Limit of Detection; Pain; Pregabalin; Reference Standards

Propofol, an intravenous anesthetic, often causes pain on injection, which can be very distressful to patients. We investigated the analgesic effect of pregabalin on pain following propofol injection, compared with lidocaine.. In a randomized, double-blind, prospective trial, 120 patients were randomized into 3 groups of 40 each; who received oral placebo and intravenous lidocaine 40 mg with venous occlusion for 1 minute (group L, n = 40), oral pregabalin 75 mg and intravenous normal saline with venous occlusion for 1 minute (group LP, n = 40), and oral pregabalin 150 mg and intravenous normal saline with venous occlusion for 1 minute (group HP, n = 40) as pretreatment, followed by administration of 1% propofol 0.5 mg/kg. Pain intensity was measured on a 4-point scale (0 = no, 1 = mild, 2 = moderate, and 3 = severe pain). Any side effects associated with pretreatment substances were recorded during the first 24 hours after surgery.. A total of 120 patients completed this trial. Demographic data were similar between groups. The incidence of pain following propofol injection was significantly reduced in group HP (50%) and group L (55%) compared with group LP (92.5%) (P < 0.05, respectively). The incidences of moderate pain in group HP (12.5%) and group L (15%) were significantly decreased compared with group LP (37.5%; both, P < 0.05). There were no significant differences in the incidence of side effects such as headache and dizziness between groups.. Pretreatment with oral pregabalin 150 mg and intravenous lidocaine 40 mg with venous occlusion equally reduced pain from propofol injection.

Topics: Adult; Analgesics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Lidocaine; Male; Pain; Pregabalin; Propofol

To test the effects of pregabalin on the induction of neurogenic claudication.. This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory-Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire.. No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = -1.08 [95% confidence interval -2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo.. Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis.. This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test.

Topics: Aged; Analgesics; Cross-Over Studies; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Female; gamma-Aminobutyric Acid; Humans; Lumbar Vertebrae; Male; Middle Aged; Outcome Assessment, Health Care; Pain; Pain Measurement; Pregabalin; Spinal Stenosis; Surveys and Questionnaires; Time Factors

To determine the time to immediate and sustained clinical improvement in pain and sleep quality with pregabalin in patients with fibromyalgia.. A post hoc analysis of four 8- to 14-week phase 2-3, placebo-controlled trials of fixed-dose pregabalin (150-600 mg/day) for fibromyalgia, comprising 12 pregabalin and four placebo treatment arms.. A total of 2,747 patients with fibromyalgia, aged 18-82 years.. Pain and sleep quality scores, recorded daily on 11-point numeric rating scales (NRSs), were analyzed to determine time to immediate improvement with pregabalin, defined as the first of ≥2 consecutive days when the mean NRS score was significantly lower for pregabalin vs placebo in those treatment arms with a significant improvement at endpoint, and time to sustained clinical improvement with pregabalin, defined as a ≥1-point reduction of the baseline NRS score of patient responders who had a ≥30% improvement on the pain NRS, sleep NRS, or Fibromyalgia Impact Questionnaire (FIQ) from baseline to endpoint, or who reported "much improved" or "very much improved" on the Patient Global Impression of Change (PGIC) at endpoint.. Significant improvements in pain and sleep quality scores at endpoint vs placebo were seen in 8/12 and 11/12 pregabalin treatment arms, respectively (P < 0.05). In these arms, time to immediate improvements in pain or sleep occurred by day 1 or 2. Time to sustained clinical improvement occurred significantly earlier in pain, sleep, PGIC, and FIQ responders (P < 0.02) with pregabalin vs placebo.. Both immediate and sustained clinical improvements in pain and sleep quality occurred faster with pregabalin vs placebo.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Pregabalin; Sleep; Time Factors; Young Adult

This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking.. Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures.. Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients.. Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Cross-Over Studies; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Quality of Life; Sleep; Treatment Outcome; Walking

Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.. Adult patients affected by PAOD at stages III and IV of Lèriche-Fontaine classification, who are opioid-naïve, and who have been admitted to our Acute Pain Service for intractable pain, will be eligible. Patients will be randomised to the control group, treated with standard therapy (oxycodone and pregabalin) plus placebo for 2 weeks, or to the experimental group (standard therapy plus magnesium oxide). Patients will be evaluated on days 0, 2, 4, 6, 8, 12 and 14; the following information will being collected: daily oxycodone dose; average and maximum pain (Numerical Rating Scale); pain relief (Pain Relief Scale); characteristics of the pain (Neuropathic Pain Scale); impact of pain on the patient's daily activities (Brief Pain Inventory). The primary outcome will be oxycodone dosage needed to achieve satisfactory analgaesia on day 14. Secondary outcomes will be pain relief on day 2, time needed to achieve satisfactory analgaesia and time needed to achieve a pain reduction of 50%. A sample size calculation was performed for the primary outcome, which estimated a required sample size of 150 patients (75 per group).. Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy. Trial results will be disseminated through scientific journal manuscripts and scientific conference presentations.. NCT02455726.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Arterial Occlusive Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Italy; Linear Models; Magnesium; Male; Middle Aged; Oxycodone; Pain; Pain Measurement; Pregabalin; Research Design; Young Adult

Behavioral disturbances and pain are common in nursing home (NH) patients with dementia. An association between pain and increased agitation has been suggested, and recently a significant reduction of agitation has been demonstrated by pain treatment in patients with moderate to severe dementia. We now examined which specific agitated behaviors respond to individualized pain treatment.. Cluster randomized clinical trial.. 60 clusters (i.e., clusters defined as single independent NH units) in 18 NHs within five municipalities of Western Norway.. 352 patients with moderate to severe dementia and clinically significant behavioral disturbances.. The control group received usual treatment and care. According to a predefined scheme for 8 weeks, all patients in the intervention group received individual daily pain treatment with acetaminophen, extended release morphine, buprenorphine transdermal patch, and/or pregabaline.. Cohen-Mansfield Agitation Inventory subscales and items.. Analyses demonstrated that Factor 3 (Verbally agitated behaviors) showed the largest significant difference (DF = 1204.0, t = -4.308, p <0.001), followed by Factor 2 (Physically non-aggressive behaviors) (DF = 1198.0, t = -2.672, p = 0.008), and Factor 1 (Aggressive behaviors) (DF = 1196.0, t = -2.093, p = 0.037) after 8 weeks, by a linear random intercept mixed model in two-way repeated-measures configuration with adjustment for heteroscedasticity.. We found that verbal agitation behaviors such as complaining, negativism, repetitious sentences and questions, constant request for attention, and cursing or verbal aggression responded to pain treatment. In addition, restlessness and pacing were sensible to analgesics. Such behaviors should therefore lead to an assessment of pain, and pain treatment. Further studies comparing how pain treatment should be balanced against other strategies including psychotropic drugs are needed.

Topics: Acetaminophen; Aged, 80 and over; Analgesics; Buprenorphine; Delayed-Action Preparations; Dementia; Female; gamma-Aminobutyric Acid; Humans; Male; Morphine; Norway; Nursing Homes; Pain; Pain Management; Pregabalin; Psychomotor Agitation; Transdermal Patch

In prior studies, pregabalin reduced rectal or colonic pain in patients with irritable bowel syndrome and healthy adults, suggesting reduction of afferent function.. To assess effects of pregabalin on colonic compliance, sensory and motor functions in patients with constipation-predominant irritable bowel syndrome.. In a pilot, double-blind, placebo-controlled, parallel-group study, we tested oral pregabalin, 200mg, in 18 patients with constipation-predominant irritable bowel syndrome. With a barostatically controlled polyethylene balloon in the left colon, we assessed sensation thresholds and colonic compliance using ascending method of limits, sensation ratings over 4 levels of distension, fasting and postprandial colonic tone and phasic motility. Analysis of covariance (adjusted for the corresponding pre-drug response) was used to compare placebo and pregabalin. After 45% participants completed studies, we conducted an interim analysis to assess the conditional power to detect pre-specified treatment effects given the observed variation and treatment group differences based on the planned sample size for the trial.. Pregabalin did not significantly affect colonic compliance, sensation thresholds, sensation ratings, fasting or postprandial tone or motility index. The study was stopped for futility to detect an effect on visceral pain with the planned design and sample size.. Pregabalin, 200mg, might not reduce distension-related colonic pain in constipation-predominant irritable bowel syndrome patients.

Topics: Adult; Analgesics; Colon; Compliance; Constipation; Double-Blind Method; Female; gamma-Aminobutyric Acid; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Pain; Pilot Projects; Pregabalin; Sensation; Sensory Thresholds; Treatment Outcome

The intradermal capsaicin pain model has been used to evaluate analgesic effects of a variety of drugs. Using the sequential up-down method, we examined the analgesic effects of pregabalin on intradermal capsaicin pain. Using a double-blind, placebo-controlled, crossover study, healthy adult men were randomized to oral pregabalin or placebo on the first visit and returned for the opposite treatment after a washout period. Dosing was set by the Dixon sequential up-down method; that is, a greater or less than 30% reduction in capsaicin pain decreased or increased the dose, respectively, by a fixed interval for the next subject. The median effective dose (ED50) was derived once 7 changes in dose direction occurred. Secondary outcome measures included secondary hyperalgesia and tactile and thermal allodynia, and their respective areas (cm(2)). Thirteen subjects were required to derive the pregabalin ED50: 252 mg (95% confidence interval 194, 310 mg). Most common side effects were drowsiness (46%), euphoria (31%), and dizziness (7%). Those with ≥30% pain reduction as compared to placebo also had similar reductions in secondary outcome measures. The intradermal capsaicin pain model can be used to efficiently derive the pregabalin ED50, but well-powered dose-response curve studies are needed for comparison and validation.. Using the Dixon sequential up-down method, the ED50 of pregabalin on intradermal capsaicin induced pain was successfully calculated (252 mg) using only 13 subjects.

Topics: Adult; Analgesics; Capsaicin; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Hyperalgesia; Male; Middle Aged; Pain; Pain Threshold; Pregabalin; Young Adult

Pain is frequent and distressing in people with dementia, but no randomized controlled trials have evaluated the effect of analgesic treatment on pain intensity as a key outcome.. Three hundred fifty-two people with dementia and significant agitation from 60 nursing home units were included in this study. These units, representing 18 nursing homes in western Norway, were randomized to a stepwise protocol of treating pain (SPTP) or usual care. The SPTP group received acetaminophen, morphine, buprenorphine transdermal patch and pregabalin for 8 weeks, with a 4-week washout period. Medications were governed by the SPTP and each participant's existing prescriptions. We obtained pain intensity scores from 327 patients (intervention n = 164, control n = 163) at five time points assessed by the primary outcome measure, Mobilization-Observation-Behaviour-Intensity-Dementia-2 (MOBID-2) Pain Scale. The secondary outcome was activities of daily living (ADL). We used a linear intercept mixed model in a two-way repeated measures configuration to assess change over time and between groups.. The SPTP conferred significant benefit in MOBID-2 scores compared with the control group [average treatment effect (ATE) -1.388; p < 0.001] at week 8, and MOBID-2 scores worsened during the washout period (ATE = -0.701; p = 0.022). Examining different analgesic treatments, benefit was conferred to patients receiving acetaminophen compared with the controls at week 2 (ATE = -0.663; p = 0.010), continuing to increase until week 8 (ATE = -1.297; p < 0.001). Although there were no overall improvements in ADL, an increase was seen in the group receiving acetaminophen (ATE = +1.0; p = 0.022).. Pain medication significantly improved pain in the intervention group, with indications that acetaminophen also improved ADL function.

Topics: Acetaminophen; Activities of Daily Living; Aged; Aged, 80 and over; Analgesics; Buprenorphine; Clinical Protocols; Dementia; Female; gamma-Aminobutyric Acid; Humans; Male; Morphine; Norway; Nursing Homes; Pain; Pain Management; Pain Measurement; Pregabalin; Transdermal Patch; Treatment Outcome

This multicentre, double-blind, parallel-group study in diabetic peripheral neuropathic pain addressed whether, in patients not responding to standard doses of duloxetine or pregabalin, combining both medications is superior to increasing each drug to its maximum recommended dose. For initial 8-week therapy, either 60 mg/day duloxetine (groups 1, 2) or 300 mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120 mg/day duloxetine (group 1), a combination of 60 mg/day duloxetine and 300 mg/day pregabalin (groups 2, 3), or 600 mg/day pregabalin (group 4). Primary outcome (Brief Pain Inventory Modified Short Form [BPI-MSF] 24-hour average pain change after combination/high-dose therapy) was analyzed comparing combination (groups 2, 3 pooled) with high-dose monotherapy (groups 1, 4 pooled). Secondary end points included response rates, BPI-MSF severity items, and comparison of duloxetine and pregabalin in BPI-MSF average pain. Eight hundred four patients were evaluated for initial therapy and 339 for combination/high-dose therapy. There were no significant differences between combination and high-dose monotherapy regarding BPI-MSF average pain (mean change: combination: -2.35; high-dose monotherapy: -2.16; P = 0.370) and most secondary end points, which, however, consistently favoured combination therapy. Fifty-percent response rates were 52.1% for combination and 39.3% for high-dose monotherapy (P = 0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60 mg/day duloxetine was found superior to 300 mg/day pregabalin (P < 0.001). Both drugs and their combination were well tolerated. Although not significantly superior to high-dose monotherapy, combination therapy was considered to be effective, safe, and well tolerated.

Topics: Aged; Analgesics; Diabetic Neuropathies; Double-Blind Method; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; gamma-Aminobutyric Acid; Humans; Internationality; Male; Middle Aged; Pain; Pregabalin; Thiophenes; Treatment Outcome

The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only.. A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life.. Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items.. The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs.

Topics: Analgesics; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Italy; Male; Morphine; Neoplasms; Pain; Pain Measurement; Palliative Care; Pregabalin; Treatment Outcome

Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown.. To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in healthy humans.. Placebo-controlled, double-blind, randomised, cross-over study of 15 healthy volunteers (six women, age 21-56 years). After oesophageal manometry, baseline pain thresholds (PTs) to proximal oesophageal electrical stimulation were determined using bipolar ring electrodes. A 30-min infusion of HCl was performed in the distal oesophagus followed by PT measurements at 30 and 90 min. This protocol was repeated after administration of pregabalin (dosing schedule: 75 mg twice daily for 3 days then 150 mg twice daily for 1 day and then 150 mg on the morning of study) or placebo.. T0 PTs were similar in patients after receiving placebo or pregabalin [mean (s.d.) 32.9 mA (20.5) vs. 34.1 (15.7), P = 0.42]. Pregabalin reduced development of acid-induced hypersensitivity in the proximal oesophagus at 30 min [mean change in PT (C.I.) placebo -6.2 mA (-11.3 to +1.3) vs. pregabalin +0.20 mA (-2.7 to +3.3)] and 90 min [placebo -3.7 mA (-10.0 to +2.0) vs. pregabalin +0.7 mA (-4.7 to 7.3)] overall P = 0.001. Pregabalin reduced median visual analogue scale score for acid-induced pain (1/10 vs. placebo 3/10, P = 0.027).. Pregabalin attenuates development of secondary hypersensitivity in the proximal oesophagus after distal oesophageal acidification; it may thus have a role in treatment of patients with proven oesophageal pain hypersensitivity.

Topics: Adult; Analgesics; Cross-Over Studies; Double-Blind Method; Esophageal Diseases; Female; gamma-Aminobutyric Acid; Humans; Hydrochloric Acid; Hydrogen-Ion Concentration; Hypersensitivity; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Pregabalin; Treatment Outcome; Young Adult

To assess the effect of pregabalin on polysomnographic (PSG) measures of sleep and patient-rated sleep, tiredness, and pain in fibromyalgia patients.. We performed a randomized, double-blind, placebo-controlled, 2-period crossover PSG study. Patients ages ≥18 years with fibromyalgia satisfied subjective and objective sleep disturbance criteria prior to randomization. Eligible patients were randomized (1:1) to pregabalin (300-450 mg/day) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose-adjustment and dose-maintenance phase, with a 2-week taper/washout between periods. In-laboratory PSGs were recorded during 2 consecutive nights at screening and at the end of each crossover period. The primary end point was the difference in sleep maintenance defined by PSG-recorded wake after sleep onset (WASO; minutes) between 4 weeks of treatment with pregabalin and with placebo. Other PSG measures; patient-rated sleep, tiredness, and pain; and tolerability were assessed.. Of 119 patients randomized (103 women [86.6%], mean age 48.4 years), 102 (85.7%) completed both periods. Patients treated with pregabalin showed a reduction in PSG-determined WASO versus treatment with placebo (week 4 difference: -19.2 minutes [95% confidence interval (95% CI) -26.7, -11.6]; P < 0.0001). Pain score improved (decreased) with pregabalin versus placebo treatment at all 4 weeks (week 4 difference: -0.52 [95% CI -0.90, -0.14]; P = 0.0084). Modest (ρ = <0.3) but significant correlations were found between PSG sleep assessments and ratings of pain and sleep quality. Frequently reported all-causality adverse events (pregabalin versus placebo) were: dizziness (30.4% versus 9.9%), somnolence (20.5% versus 4.5%), and headache (8.9% versus 8.1%).. Patients with fibromyalgia treated with pregabalin had statistically significant and meaningful improvements in sleep, as assessed by PSG. Patients with fibromyalgia also reported decreased daily pain. Pregabalin was well tolerated.

Topics: Adult; Aged; Analgesics; Comorbidity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Fatigue; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Polysomnography; Pregabalin; Self Report; Sleep Wake Disorders; Treatment Outcome

Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes.. This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.. Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.. It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.

Topics: Adult; Analysis of Variance; Capsaicin; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Hyperalgesia; Injections, Intradermal; Male; Middle Aged; Minocycline; Pain; Pregabalin; Sciatica; Time Factors; Treatment Outcome

Chronic diabetic peripheral neuropathic pain (DPNP) is difficult to treat, with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance. Secondary parameters, such as quality of sleep and mood, may also be important for successful DPNP management. The objectives of this study were to compare the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and their effect on polysomnographic sleep, daytime functioning, and quality of life in patients with DPNP.. This was a double-blind, randomized, parallel group investigation of type 1 and 2 diabetic subjects with DPNP. Each treatment group had a single-blind, 8-day, placebo run-in followed by 14 days of lower-dose and 14 days of higher-dose medication. At the end of each dose titration period, subjective pain, sleep, and daytime functioning were assessed during a 2-day residential period.. All medications reduced pain when compared with placebo, but no one treatment was superior to any other. For sleep, pregabalin improved sleep continuity (P < 0.001), whereas duloxetine increased wake and reduced total sleep time (P < 0.01 and P < 0.001). Despite negative effects on sleep, duloxetine enhanced central nervous system arousal and performance on sensory motor tasks. There were no significant safety findings; however, there was a significantly higher number of adverse events in the pregabalin treatment group.. There was no significant difference in analgesic efficacy between amitriptyline, duloxetine, and pregabalin. However, there were significant differences in the secondary parameters, which may be of relevance when deciding the optimal treatment for DPNP.

Topics: Aged; Amitriptyline; Diabetic Neuropathies; Double-Blind Method; Duloxetine Hydrochloride; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pregabalin; Quality of Life; Sleep; Thiophenes; Treatment Outcome

Pregabalin, a high-affinity ligand for α2δ subunits of voltage-gated calcium channels, is a novel pharmacotherapy for chronic pain, partial seizures, and other disorders. The present study investigated the population pharmacokinetics of pregabalin following single and multiple doses in healthy volunteers and patient populations.. Using nonlinear mixed-effect modeling, 5,583 plasma pregabalin concentration-time samples from 1,723 subjects were analyzed: 2,868 samples from healthy volunteers or subjects with renal impairment (n = 123), 1,513 from patients with partial seizures (n = 626), and 1,202 from patients with chronic pain (n = 974). A one-compartment model with first-order elimination and absorption processes and absorption lag time was used.. This pharmacostatistical model showed that: (1) pregabalin oral clearance (CL/F) was directly proportional to creatinine clearance (CLcr), but was independent of gender, race, age, female hormonal status, daily dose, and dosing regimen; (2) apparent volume of distribution was dependent on body weight and gender; (3) absorption rate was decreased when given with food; and (4) coadministration with marketed antiepileptic drugs (AEDs) had no significant effect on pregabalin CL/F.. Pregabalin CL/F is related to CLcr, and this relationship is similar among healthy volunteers and patients with either partial seizures or chronic pain disorders. The only factor having a clinically significant influence on steady-state plasma pregabalin concentrations is renal function.

Topics: Adult; Aged; Algorithms; Analgesics; Anticonvulsants; Chronic Disease; Databases, Factual; Dose-Response Relationship, Drug; Drug Interactions; Epilepsies, Partial; Ethnicity; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Models, Statistical; Nonlinear Dynamics; Pain; Population; Pregabalin; Reproducibility of Results

Pregabalin has demonstrated efficacy in several forms of neuropathic pain, but its long-term efficacy in central post-stroke pain (CPSP) is unproven. We evaluated the efficacy and safety of pregabalin versus placebo in patients with CPSP. A 13-week, randomized, double-blind, multicenter, placebo-controlled, parallel group study of 150 to 600 mg/day pregabalin was conducted in patients aged ≥18 years with CPSP. The primary efficacy endpoint was the mean pain score on the Daily Pain Rating Scale over the last 7 days on study drug up to week 12 or early termination visit. Secondary endpoints included other pain parameters and patient-reported sleep and health-related quality-of-life measures. A total of 219 patients were treated (pregabalin n=110; placebo n=109). A mean pain score at baseline of 6.5 in the pregabalin group and 6.3 in the placebo group reduced at endpoint to 4.9 in the pregabalin group and 5.0 in the placebo group (LS mean difference=-0.2; 95% CI=-0.7, 0.4; P=0.578). Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including MOS-sleep, HADS-A anxiety, and clinician global impression of change (CGIC) P<0.05. Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 9 (8.2%) of pregabalin patients versus 4 (3.7%) of placebo patients. Although pain reductions at endpoint did not differ significantly between pregabalin and placebo, improvements in sleep, anxiety, and CGIC suggest some utility of pregabalin in the management of CPSP.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Stroke; Treatment Outcome

The effect of pregabalin on acute herpes zoster pain has not been previously evaluated.. In a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster.. Over 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant.. Compared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA.. ClinicalTrials.gov Identifier: NCT00352651.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analgesics; California; Cross-Over Studies; Double-Blind Method; Female; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Hyperalgesia; Male; Middle Aged; Pain; Pain Measurement; Patient Selection; Pregabalin; Treatment Outcome; Young Adult

This randomised, double-blind, placebo-controlled trial assessed the efficacy and tolerability of pregabalin to alleviate the neuropathic component of moderate to severe burn pain. Patients aged 18 to 65 years admitted to a burns unit with a 5% or greater total body surface area burn injury were screened to participate in the trial. Using the Neuropathic Pain Scale (NPS), patients scoring 4 or higher on 'hot' pain or 'sharp' pain were invited to participate. Consenting patients were randomly assigned to receive pregabalin or placebo for 28 days with individual dose titration commencing at 75 mg twice daily to a maximum pregabalin dose of 300 mg twice daily. The primary outcome measure was the patients' daily response to the sharp and hot pain of the NPS. Secondary outcome measures included the remaining elements of the NPS, daily opioid requirement, length of hospital stay, pain at 6 months, and side effects of nausea, vomiting, drowsiness and giddiness. For patients administered pregabalin, the primary outcome measures hot (P = .01) and sharp (P = .04) pain were significantly reduced compared with those in patients administered placebo. Secondary outcome measures of itch, unpleasantness, surface pain, and procedural pain were significantly lower (P < .05) in the pregabalin group. Adverse effects were uncommon, with no difference between the treatment groups. There was no significant difference between the pregabalin and placebo treatment groups with respect to opioid consumption, duration of hospital stay, or pain at 6 months. Pregabalin was efficacious and well tolerated in patients after severe burn injury and whose pain was characterised by features of acute neuropathic pain. In this study, pregabalin was well tolerated and significantly reduced several elements of the neuropathic pain scale including hot pain, unpleasantness of the pain, surface pain, and itch, and also significantly reduced procedural pain.

Topics: Adolescent; Adult; Aged; Analgesics; Analgesics, Opioid; Burns; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Time Factors; Treatment Outcome; Young Adult

Although trazodone is frequently used by fibromyalgia patients, its efficacy on this disease has not been adequately studied. If effective, pregabalin, whose beneficial effects on pain and sleep quality in fibromyalgia have been demonstrated, could complement the antidepressant and anxiolytic effects of trazodone. The aim of the present study was to assess the effectiveness of trazodone alone and in combination with pregabalin in the treatment of fibromyalgia.. This was an open-label uncontrolled study. Trazodone, flexibly dosed (50-300 mg/day), was administered to 66 fibromyalgia patients during 12 weeks; 41 patients who completed the treatment accepted to receive pregabalin, also flexibly dosed (75-450 mg/day), added to trazodone treatment for an additional 12-week period. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), the Brief Pain Inventory (BPI), the Short-Form Health Survey (SF-36), and the Patients' Global Improvement scale (PGI). Emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test.. Treatment with trazodone significantly improved global fibromyalgia severity, sleep quality, and depression, as well as pain interference with daily activities although without showing a direct effect on bodily pain. After pregabalin combination additional and significant improvements were seen on fibromyalgia severity, depression and pain interference with daily activities, and a decrease in bodily pain was also apparent. During the second phase of the study, only two patients dropped out due to side effects.. Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in association was good.. ClinicalTrials.gov: NCT00791739.

Topics: Adult; Analgesics; Analysis of Variance; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Anxiety; Depression; Drug Therapy, Combination; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Sleep; Spain; Surveys and Questionnaires; Time Factors; Trazodone; Treatment Outcome; Young Adult

This study evaluates the efficacy and tolerability of long-term controlled-release (CR) oxycodone + pregabalin in patients with non-cancer pain, in a real-life setting.. Patients (n = 1,051) with chronic uncontrolled non-cancer pain received CR oxycodone + pregabalin for 1 year. Pain intensity was rated on an 11-point numerical rating scale (NRS) at months 1, 2, 4, 6, 9 and 12.. Throughout the study period, the NRS score decreased significantly (baseline: 7.02 ± 1.26; 12 months: 1.45 ± 0.92; p = 0.00001). Following an initial increase in the mean daily doses of CR oxycodone (starting dose: 12.5 ± 8.4 mg) and pregabalin (starting dose: 121.7 ± 97.2 mg), dose reductions were seen for both drugs with the trend particularly evident for CR oxycodone. 23% of patients withdrew from the study, mainly due to adverse events (67.9% of withdrawn subjects). However, 19.7% of withdrawn patients were removed from the study due to complete relief from chronic pain. The combination was generally well tolerated and there were no reports of addiction.. The combination of CR oxycodone + pregabalin could represent a valuable long-term therapeutic addition to existing pharmacological options for the treatment of non-cancer pain.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Cohort Studies; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Observation; Oxycodone; Pain; Pain Measurement; Pregabalin; Time Factors; Young Adult

The aim of this randomized double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of pregabalin in combination with oxycodone or placebo, in patients with either postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN). After a 7-day washout period, 62 patients were randomized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week. Patients were then started on open-label pregabalin (75, 150, 300 and 600 mg/day) according to a forced titration dosing regimen, while continuing the same dosage of oxycodone or placebo for 4 weeks. The primary efficacy measure was a decrease in the pain-intensity score of at least 2cm and a pain score <4cm measured using a 10-cm visual analogue scale (VAS) following pregabalin dosage escalation and treatment for 4 weeks. Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale. There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain.. Peripheral neuropathic pain presents commonly in clinical practice, and 2 of its most prevalent types are PHN and PDN. Currently available treatments provide some degree of pain relief in approximately 40-60% of patients, leaving the remainder with unremitting pain. Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN, it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin.

Topics: Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid; Diabetic Neuropathies; Double-Blind Method; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Neuralgia, Postherpetic; Oxycodone; Pain; Pain Measurement; Pregabalin; Sleep; Time Factors; Treatment Outcome

The objective of this study was to evaluate the effect of patients' characteristics at baseline on the magnitude of pain response to pregabalin in patients with fibromyalgia.. Data from four randomized, multicenter, placebo-controlled clinical studies of pregabalin in patients with fibromyalgia were used for the analysis. Approved doses (300 and 450 mg/day) were pooled to enhance the sensitivity of the interaction tests. A centered covariate interaction model was used to assess the treatment effects; a noncentered model was used for estimated mean pain changes and least square means across different levels of baseline covariates. The interaction was considered significant if p < 0.10.. In total, 2061 patients (median age, 49 years; median pain score, 7.0; median duration of fibromyalgia, 83 months) were included in this analysis. No significant interaction was observed between treatment and anxiety, depression, or duration of fibromyalgia. Significant treatment by baseline mean pain (p = 0.037), treatment by baseline sleep score (p = 0.071), and treatment by age (p = 0.051) interactions were observed.. The magnitude of response to pregabalin in terms of changes in pain may depend on age, pain, and sleep levels at baseline in patients with fibromyalgia.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Anxiety; Depression; Dose-Response Relationship, Drug; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Sleep Wake Disorders; Treatment Outcome

Fibromyalgia is a prevalent and disabling disorder characterized by widespread pain and other symptoms such as insomnia, fatigue or depression. Catastrophization is considered a key clinical symptom in fibromyalgia; however, there are no studies on the pharmacological or psychological treatment of catastrophizing. The general aim of this study is to assess the effectiveness of cognitive-behaviour therapy and recommended pharmacological treatment for fibromyalgia (pregabalin, with duloxetine added where there is a comorbid depression), compared with usual treatment at primary care level.. A multi-centre, randomized controlled trial involving three groups: the control group, consisting of usual treatment at primary care level, and two intervention groups, one consisting of cognitive-behaviour therapy, and the other consisting of the recommended pharmacological treatment for fibromyalgia.. 29 primary care health centres in the city of Zaragoza, Spain.. 180 patients, aged 18-65 years, able to understand and read Spanish, who fulfil criteria for primary fibromyalgia, with no previous psychological treatment, and no pharmacological treatment or their acceptance to discontinue it two weeks before the onset of the study.. Psychological treatment is based on the manualized protocol developed by Prof. Escobar et al, from the University of New Jersey, for the treatment of somatoform disorders, which has been adapted by our group for the treatment of fibromyalgia. It includes 10 weekly sessions of cognitive-behaviour therapy. Pharmacological therapy consists of the recommended pharmacological treatment for fibromyalgia: pregabalin (300-600 mg/day), with duloxetine (60-120 mg/day) added where there is a comorbid depression).. The following socio-demographic data will be collected: sex, age, marital status, education, occupation and social class. The diagnosis of psychiatric disorders will be made with the Structured Polyvalent Psychiatric Interview. Other instruments to be administered are the Pain Catastrophizing Scale, the Hamilton tests for Anxiety and for Depression, the Fibromyalgia Impact Questionnaire (FIQ), the EuroQuol-5 domains (EQ-5D), and the use of health and social services (CSRI). Assessments will be carried out at baseline, 1, 3, and 6 months. MAIN VARIABLE: Pain catastrophizing.. The analysis will be per intent to treat. We will use the general linear models of the SPSS version 15 statistical package, to analyse the effect of the treatment on the result variable (pain catastrophizing).. It is necessary to assess the effectiveness of pharmacological and psychological treatments for pain catastrophizing in fibromyalgia. This randomized clinical trial will determine whether both treatments are effective for this important prognostic variable in patients with fibromyalgia.. Current Controlled Trials ISRCTN10804772.

Topics: Adolescent; Adult; Aged; Analgesics; Antidepressive Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Depression; Duloxetine Hydrochloride; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Middle Aged; Pain; Pain Management; Pain Measurement; Pregabalin; Psychiatric Status Rating Scales; Research Design; Spain; Thiophenes; Time Factors; Treatment Outcome; Young Adult

Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM.. Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients' global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain.. A total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48-50 years, on average had FM for 9-10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P<0.001), MOS Sleep Disturbance (P<0.01), MOS Quantity of Sleep (P<0.003), and MOS Sleep Problems Index scores (P<0.02) relative to placebo. Treatment effects for the 450mg and 600mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43-80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief.. These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients' insomnia, while the remainder occurred through the drug's analgesic activity.

Topics: Analgesics; Double-Blind Method; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Medical Records; Middle Aged; Pain; Pain Measurement; Pregabalin; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).. Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs.. EudraCT No. 2006-003132-29.. Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients' treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated.. In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

Topics: Aged; Algorithms; Analgesics; Casts, Surgical; Diabetic Neuropathies; Drug Combinations; Female; gamma-Aminobutyric Acid; Humans; Lidocaine; Male; Middle Aged; Neuralgia, Postherpetic; Osmolar Concentration; Pain; Patient Satisfaction; Pregabalin; Treatment Outcome

To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).. This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of > or = 2 points or an absolute value of < or = 4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs).. Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin.. 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

Topics: Aged; Algorithms; Analgesics; Casts, Surgical; Diabetic Neuropathies; Female; gamma-Aminobutyric Acid; Humans; Lidocaine; Male; Middle Aged; Neuralgia, Postherpetic; Osmolar Concentration; Pain; Pregabalin; Treatment Outcome

Effects of pregabalin (PGB) on patient-reported health outcomes were assessed in 65 PGB-naive subjects with trigeminal neuralgia refractory to previous analgesic therapy in a prospective, multicentre observational study carried out in primary care. Twelve weeks' monotherapy with PGB (n = 36) or add-on (n = 29), reduced baseline intensity of pain by a mean +/- S.D. of -40.0 +/- 22.1 mm [-55.4%, effect size (ES) 2.32; P < 0.0001] with 59.4% of responders (pain reduction >or= 50%), and produced 34.6 +/- 29.3 additional days with no/mild pain. Anxiety/depression symptoms decreased by -3.8 +/- 3.5 and -4.5 +/- 4.2 points (ES 0.95 and 1.02; P < 0.0001), respectively. PGB improved sleep by -17.9 +/- 19.6 points (ES 1.18; P < 0.0001) and improved patient functioning (Sheehan Disability Index) by decreasing overall scoring by -8.6 +/- 5.9 points (ES 1.59; P < 0.0001). Health state (EQ-5D) increased by 31.6 +/- 22.2 mm (ES 1.67; P < 0.0001), with 0.0388 +/- 0.0374 gained quality-adjusted life-years. In spite of the small sample size, results support the effectiveness of PGB for the improvement in pain and related health symptoms.

Topics: Analgesics; Disability Evaluation; Evidence-Based Medicine; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pregabalin; Primary Health Care; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Trigeminal Neuralgia

To compare the efficacy and safety of pregabalin and amitriptyline in alleviating pain associated with diabetic peripheral neuropathy.. A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 51). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time and pregabalin orally, at doses of 75, 150 and 300 mg twice daily, by optional titration was used. Each drug treatment was of 5 weeks. There was a placebo washout period for 3 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out.. Good, moderate and mild pain relief were noted in 21 (48%), 6 (13%) and 7 (15%) patients on pregabalin and 15 (34%), 5 (11%) and 12 (27%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physician's global assessment, McGill pain questionnaire, Likert pain scale and Patient Global Impression of Change showed no significant difference between the treatments, although improvement with both treatments was seen from the first week. Of the 52 adverse events reported, 34 (65.4%) were with amitriptyline, drowsiness being the commonest [in 19 (43%) patients]. Pregabalin caused adverse events in 18 (25%), of which drowsiness was the most common in nine (20%) patients. The preferred pregabalin dose was 150 mg twice daily.. As there are few differences between the two treatments in efficacy, pregabalin 150 mg twice daily might be the alternative choice as it is associated with fewer adverse effects in our population.

Topics: Amitriptyline; Analgesics, Non-Narcotic; Diabetic Neuropathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pregabalin; Treatment Outcome

Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).. In this randomized, double-blind, placebo-controlled trial, the primary efficacy measure was endpoint mean pain score (MPS) from daily pain diaries (11-point scale). NC velocity and sensory and motor amplitudes were assessed at baseline, endpoint, and end of follow-up (2 weeks post-treatment). At each timepoint, the median-motor, median-sensory, ulnar-sensory, and peroneal-motor nerves were evaluated. Secondary efficacy measures included weekly MPS and proportion of responders (patients achieving >or=50% reduction in MPS from baseline to endpoint). After 1-weeks' dosage escalation, pregabalin-treated patients received 300 mg BID for 12 weeks.. Eighty-two patients received pregabalin and 85 placebo. Mean durations were 10 years for diabetes and approximately 5 years for painful DPN. Pregabalin-treated patients had lower MPS than controls (mean difference, -1.28; p <.001). For all four nerves, 95% CIs for median differences in amplitude and velocity from baseline to endpoint and baseline to follow-up included 0 (ie, no significant difference vs. placebo). Significant pain improvement among pregabalin-treated patients was evident at week 1 and sustained at every weekly timepoint. More pregabalin-treated patients (49%) than controls (23%) were responders (p <.001).. Pregabalin 600 mg/d (300 mg BID) effectively reduced pain, was well tolerated, and had no statistically significant or clinically meaningful effect on NC in patients with painful DPN.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Diabetic Neuropathies; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Male; Median Nerve; Middle Aged; Neural Conduction; Pain; Pain Measurement; Peroneal Nerve; Placebos; Pregabalin; Treatment Outcome; Ulnar Nerve

Intradermal (ID) capsaicin injection in humans induces spontaneous pain, flare, primary hyperalgesia, secondary hyperalgesia, and allodynia. Secondary hyperalgesia and allodynia are a reflection of central sensitization. The effect of treatment of single doses of (1) pregabalin, 300 mg single oral dose, and (2) morphine, 10 mg IV, on the area of secondary hyperalgesia induced by ID capsaicin injection was studied by using a randomized, double-blinded, placebo-controlled, 4-period, cross-over design in 20 healthy men. Compared with active placebo diphenhydramine (50 mg oral dose), pregabalin and morphine significantly reduced the area of secondary hyperalgesia over 15 to 240 minutes after capsaicin injection (approximately 25%, P = .002 and approximately 33%, P < .001, respectively). A smaller reduction was observed when pregabalin and morphine were compared with true placebo (approximately 13%, P = .081 and approximately 24%, P = .009, respectively). Diphenhydramine, on the other hand, increased the area of secondary hyperalgesia in comparison with true placebo (approximately 16%, P = .061). The relationship between the baseline area of hyperalgesia and assay sensitivity suggests that establishing minimum entry criteria for the baseline area of hyperalgesia requirement increases the sensitivity of the assay.. These results suggest that the minimally invasive intradermal capsaicin model, when it is compared with true placebo, can potentially be used for an early assessment of relevant pharmacology of novel analgesic compounds in healthy subjects. This platform may provide a means to rapidly assess new analgesics and enhance dose selection and decision-making during clinical development.

Topics: Adolescent; Adult; Alkaloids; Analgesics; Analgesics, Opioid; Analysis of Variance; Capsaicin; Cross-Over Studies; Diphenhydramine; Double-Blind Method; Drug Administration Routes; gamma-Aminobutyric Acid; Humans; Hyperalgesia; Hypnotics and Sedatives; Injections, Intradermal; Injections, Intravenous; Male; Middle Aged; Morphine; Pain; Pain Measurement; Placebos; Pregabalin; Treatment Outcome; Young Adult

The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P=0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain.

Topics: Central Nervous System Diseases; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Quality of Life

To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM.. This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance.. Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events.. Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM.

Topics: Adolescent; Adult; Aged; Analgesics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Patient Satisfaction; Pregabalin; Severity of Illness Index; Sleep

Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the alpha(2)delta ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity.. To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients.. Twenty-six patients with Rome-II-defined IBS (aged 18-46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1-3, 100 mg tid days 4-7, 150 mg tid days 8-11; fixed 200 mg tid days 12-21 +/-4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of

Topics: Administration, Oral; Adolescent; Adult; Analgesics; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Pregabalin; Pressure; Rectum; Sensation; Sensory Thresholds

To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain.. Using stochastic simulation, we estimated the cost-effectiveness of PGB 150-600 mg/d vs. GBP 900-3600 mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0-10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with >or= 30% and >or= 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs.. Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with >or= 30% reduction in pain intensity, 9 (0.5) days with >or= 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were euro 1049 (euro 35) for PGB and euro 951 (euro 38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of euro 12 (95% confidence interval, euro 1-24) per additional day with no or mild pain, euro 431 (dominant-euro 876) per additional patient with no or mild pain, and euro 20 535 (euro 1607-40 345) per QALY gained.. According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.

Topics: Amines; Cost-Benefit Analysis; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Double-Blind Method; Gabapentin; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Pain; Pain Measurement; Placebos; Pregabalin

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS.. This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.. Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P /=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.. Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebos; Pregabalin; Quality of Life; Sleep Wake Disorders; Treatment Outcome

The following case report discusses probable clitoral priapism secondary to duloxetine and pregabalin. While this is a rare adverse effect, it is possible given the mechanism of action and potentiating effects of the combined therapy. This adverse drug reaction was reported to MedWatch and shows that additional research into the physiology of clitoral erection is warranted given the scarcity of information on how drugs influence this reaction.. A 53-year-old African American female with uncontrolled anxiety was started on duloxetine. Pregabalin was added 1 month later due to continued feelings of anxiety. Three weeks later, the patient reported symptoms of clitoral pain, as well as a swollen, tender, and erect clitoris. These adverse effects remained for 4 days, prompting the patient to present to the emergency department where a physical exam was completed with no significant finding except as noted above. Pregabalin was immediately discontinued by the attending physician based on the probability that the swelling was likely drug-induced clitoral priapism. During follow-up, the patient continued to note clitoral erection and pain. The psychiatric pharmacist tapered off duloxetine over 2 weeks with resolution of symptoms. In an examination of the mechanism of action of both drugs, pregabalin can amplify duloxetine's inhibitory effects on voltage-dependent calcium channels. It is likely this mechanism that causes smooth muscle relaxation and led to clitoral priapism.. This case suggests that pharmacological agents affecting vasoconstriction through serotonergic receptors or calcium-dependent channels can also influence clitoral erection.

Topics: Analgesics; Clitoris; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Pain; Pregabalin; Priapism; Probability

Two statements from national organizations outline recommended minimum effective doses of gabapentin and pregabalin for the treatment of diabetic peripheral neuropathy (DPN). However, studies of real-world gabapentinoid dosing demonstrate that the recommended dose targets are frequently not met and do not consider renal insufficiency. This study aimed to characterize gabapentinoid prescribing patterns in patients receiving primary care at two internal medicine clinics within an academic medical center. This retrospective chart review included adult outpatients who were newly initiated on gabapentin or pregabalin between October 1, 2017 and October 1, 2020 and reviewed for 12 months. A total of 1,221 patients were included in the study with 1,079 (88.4%) prescribed gabapentin and 142 (11.6%) prescribed pregabalin. Only 22.4% of patients prescribed gabapentin and 33.3% of patients prescribed pregabalin with adequate renal function met the minimum effective dosing of gabapentin 1800 mg per day and pregabalin 300 mg per day provided by the American Diabetes Association (ADA) and American Academy of Neurology (AAN). This study supports the need for optimization of gabapentinoid dosing to ensure an adequate trial at the minimum effective dose is completed.

Topics: Adult; Amines; Analgesics; Gabapentin; Humans; Outpatients; Pain; Pregabalin; Retrospective Studies

Topics: Amitriptyline; Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Duloxetine Hydrochloride; Humans; Pain; Pregabalin

Topics: Analgesics; Animals; Anoctamin-1; Carboxylic Acids; HEK293 Cells; Humans; Hyperalgesia; Mice; Neoplasm Proteins; Pain

To assess painful diabetic neuropathy (PDN) as a cause for refractory ear pain in type 2 diabetics.. An observational prospective case series study.. Otolaryngology departments of tertiary referral hospitals from November 2019 to January 2021.. Sixty-eight patients with type 2 diabetes with refractory ear pain of more than 1-month duration not responding to the routine analgesics.. Diagnostic intervention.. The primary outcome measure was the prevalence of painful diabetic neuropathy among different causes of ear pain in the study sample of type II diabetics with refractory ear pain with an assessment of the response of these cases to routine neuropathic pain treatment with pregabalin.. Fifteen out of 68 (22.1%) were diagnosed as having painful diabetic neuropathy based on the "Douleur Neuropathique en 4 Questions" (DN4) questionnaire with its mean value being 6.47±1.19. There was a highly significant improvement of the 10 items of painful diabetic neuropathy scales after 1 month of treatment ( p < 0.001 for all). There was a significant positive correlation between the Hemoglobin A1c level and duration of diabetes at one hand and intensity of pain derived from the painful diabetic neuropathy scale at the other hand ( p = 0.0002, and p = 0.032 respectively).. Painful diabetic neuropathy showed a potential correlation with refractory ear pain in type II diabetic patients with significant improvement after painful diabetic neuropathy treatment. Further studies are needed to confirm these findings.

Topics: Analgesics; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Earache; Humans; Pain; Pregabalin

Here, we describe a case of a patient with multiple myeloma who reported symptoms of lucid dreams. This patient was taking methadone for neoplasm related pain. The patient was also taking pregabalin which was initially started at dosing of 50 mg taken orally three times a day. Five days after initiation of pregabalin, the dosing was increased to 100 mg taken orally three times daily. The patient developed lucid dreams during a hospital stay and methadone was initially thought to be the cause of her lucid dreams. Methadone dosing was decreased with no success, and her lucid dreams persisted. On the patient's thirteenth day of hospital admission, the pregabalin dose was decreased from 100 mg three times a day to 75 mg twice daily. Five days later, the pregabalin was decreased from 75 mg twice daily to 50 mg twice daily. Pregabalin was continued for five more days and then discontinued. Resolution of the lucid dreams occurred following discontinuation of pregabalin. To our knowledge, this is the first reported case of an association between pregabalin and lucid dreams. Given that pregabalin is a widely used medication, we found this case to be relevant to describe this unique presentation.

Topics: Dreams; Female; Humans; Methadone; Pain; Pregabalin

This study aims to determine the treatment preferences of physicians interested in fibromyalgia treatment and to investigate their hesitations about prescribing pregabalin.. Our survey study was conducted between February 5 and 20, 2021. The survey forms were sent to the known email addresses and phone numbers of 1569 physical medicine and rehabilitation (PMR), algology, and rheumatology physicians. The replies to the surveys were checked for possible resubmissions. The pooled data were evaluated with the SPSS 22.0 statistical package program. Frequency distributions were calculated and presented as n, %.. Four hundred and six PMR, rheumatology, and algology specialists fulfilled the study forms. About 59.0% of physicians stated that they prefer duloxetine as the first-line agent of fibromyalgia syndrome (FMS) treatment. Pregabalin was only 6.0% of the physicians' first choice for FMS. About 35.0% of the participating physicians stated that the PMR department should follow up FMS patients. About 44.3% of the participants noted that they refer FMS patients to other departments which interested in FMS treatment and do not want to follow-up FMS patients. About 81% agreed that pregabalin causes addiction. About 36.7% stated that at least 20% of the patients could abuse pregabalin and 97.8% of physicians stated that they were prejudiced about prescribing pregabalin to prisoners. Approximately two of the three physicians experienced an act of violence in their hospital regarding pregabalin prescribing.. These data showed that the 'Pregabalinophobia' should be accepted. This condition is associated with life safety concerns of the physician not only from unreliability of the drug. It seems that the doctors have valid reasons to develop this prejudice.

Topics: Analgesics; Fibromyalgia; Humans; Pain; Physicians; Pregabalin

Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events.. This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts.. Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease.. In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Topics: Amines; Analgesics; Cardiovascular Diseases; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Gabapentin; gamma-Aminobutyric Acid; Heart Disease Risk Factors; Heart Failure; Humans; Myocardial Infarction; Pain; Peripheral Vascular Diseases; Pregabalin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Stroke

Corneal nerve damage after laser epithelial keratomileusis (LASEK) is thought to be the cause of dry eye and pain. Therefore, we investigated whether taking pregabalin (Lyrica), which reduces peripheral neuropathic pain, alleviates corneal nerve sensitivity after surgery and reduces dry eye and pain.. Patients were treated with pregabalin (150 mg two times a day for 15 days) from the day before surgery onward and compared with those who did not receive the medications. Before surgery, the severity of dry eye was assessed. Then, corneal sensitivity was assessed by esthesiometry and pain was assessed according to the Visual Analogue Scale. Images of the sub-basal nerve plexus were analysed using confocal microscopy to evaluate nerve regeneration at 6 months.. Forty eyes in the pregabalin group and 40 eyes in the control group were included in this study. No significant differences regarding the severity of dry eye, corneal sensitivity test results and nerve fibre density existed between the two groups until 6 months. The pregabalin group showed significantly reduced pain at 1 week.. Taking pregabalin during LASEK surgery may affect corneal nerve sensitivity and reduce pain. However, for up to 6 months thereafter, corneal sensitivity and nerve fibre density are not significantly different from findings in the control group, so pregabalin does not seem to affect nerve regeneration or structural changes.

Topics: Cornea; Dry Eye Syndromes; Humans; Keratomileusis, Laser In Situ; Pain; Pregabalin

Gabapentinoid drugs (gabapentin and pregabalin) are increasingly used for pain as both patients and physicians seek opioid-sparing or opioid-reducing strategies. Such widespread use for off-label pain indications is not supported by robust evidence, risking potential unintended consequences relating to adverse events. This study evaluated adult patients who were administered at least one dose of a gabapentinoid during a hospital admission between January 1, 2018 and December 31, 2018. The primary objective was to compare the difference in administered gabapentinoid total daily dose in patients with or without concomitant opioid. Secondary objectives included comparing the difference in sedation documentation, renal function, fall risk scores using the Hester Davis Fall Risk Scale, and central nervous system (CNS) related side effects between the 2 study groups. Four hundred and ninety nine patients (pregabalin n = 32 and gabapentin n = 467) were included. Due to small sample size for pregabalin, outcome results were presented for gabapentin only. The mean gabapentin total daily dose was 706 mg (SD = 614 mg) in the non-opioid group versus 860 mg (SD = 553 mg) in the opioid group (p = 0.007). There was more sedation documentation observed in the opioid group (p < 0.001). Patients in the opioid group used a significantly higher gabapentinoid total daily dose. Sedation documentation was significantly more in the opioid group despite commonly reported CNS related adverse events with gabapentinoids.

Topics: Adult; Analgesics; Analgesics, Opioid; Gabapentin; Hospitalization; Humans; Pain; Pregabalin

Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed.. We developed a method to study thermal preference of oxaliplatin-treated mice and assessed analgesic activity of intraperitoneal duloxetine and pregabalin used at 30 mg/kg. A prototype analgesiameter and a broad range of temperatures (0-45 °C) were used. Advanced methods of image analysis (deep learning and machine learning) enabled us to determine the effectiveness of analgesics. The loss or reversal of thermal preference of oxaliplatin-treated mice was a measure of analgesia.. Duloxetine selectively attenuated cold-induced pain at temperatures between 0 and 10 °C. Pregabalin-treated mice showed preference towards a colder plate of the two used at temperatures between 0 and 45 °C.. Unlike duloxetine, pregabalin was not selective for temperatures below thermal preferendum. It influenced pain sensation at a much wider range of temperatures applied. Therefore, for the attenuation of cold hypersensitivity duloxetine seems to be a better than pregabalin therapeutic option. We propose wide-range measurements of thermal preference as a novel method for the assessment of analgesic activity in mice.

Topics: Analgesics; Animals; Antineoplastic Agents; Cold Temperature; Disease Models, Animal; Duloxetine Hydrochloride; Hot Temperature; Hyperalgesia; Male; Mice; Oxaliplatin; Pain; Pain Measurement; Pregabalin; Temperature

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Benzothiazoles; Binding Sites; Ganglia, Spinal; HEK293 Cells; Humans; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Docking Simulation; Molecular Structure; Neurogenic Inflammation; Pain; Pancreatitis; Potassium Channels, Tandem Pore Domain; Protein Binding; Rats, Sprague-Dawley; Structure-Activity Relationship

It is often assumed that there are 2 types of pain patients: those who respond well to efficacious pain therapies and those who do not respond at all, with few people in the middle. This assumption is based on research that claims that changes in pain intensity have a bimodal distribution. The claim of bimodality has led to calls for a change in how pain clinical trials are designed and analyzed, eg, performing "responder" analyses instead of comparing group mean values to evaluate the treatment effect. We analyzed data from 4 clinical trials, 2 each of duloxetine and pregabalin, for chronic musculoskeletal and neuropathic pain conditions to critically examine the claim of bimodality of the distribution of change in pain intensity. We found that the improper construction of histograms, using unequal bin widths, was the principal flaw leading to the bimodality claim, along with the use of the oft-criticized baseline observation carried forward method for imputing missing data also serving as a contributing factor. Properly constructed histograms of absolute change in pain intensity using equal bin widths, combined with more principled methods for handling missing data, resulted in distributions that had a more unimodal appearance. Although our findings neither support nor refute the hypothesis that distinct populations of "responders" and "nonresponders" to pain interventions exist, the analyses presented in earlier work do not provide support for this hypothesis, nor for the recommendation that pain clinical trials prioritize "responder" analyses, a less efficient analysis strategy.

Topics: Analgesics; Clinical Trials as Topic; Duloxetine Hydrochloride; Female; Humans; Male; Pain; Pain Management; Pain Measurement; Pregabalin; Research Design; Treatment Outcome

Severe burn patients undergo prolonged administration of sedatives and analgesics for burn care. There are currently no guidelines for the dose adaptation of sedation-analgesia in severe burn patients.. We performed a before-after 2-center study to demonstrate the feasibility and efficacy of a sedation-analgesia scale-based protocol in severely burned patients receiving ≥24h of invasive mechanical ventilation. Before the intervention, continuous infusion of hypnotic and morphine derivatives was continued. During the Intervention phase, general anesthesia was relayed from day 1 by RASS/BPS-titrated continuous infusion of hypnotic and morphine derivatives and with short half-life drugs adminstered for daily burn dressings. The primary outcome was the duration of invasive mechanical ventilation in the ICU.. Eighty-seven (46.2%) patients were included in the Control phase and 101 (53.7%) in the Intervention phase. The median burned cutaneous surface was 20% [11%-38%] and median ABSI was 7 [5-9]. The durations of hypnotic and opioid infusions were not statistically different between the 2 phases (8 days [2-24] vs. 6 days [2-17] (P=0.3) and 17 days [4-32] vs. 8 days [3-23] (P=0.06), respectively). The duration of mechanical ventilation was 14 days [3-29] in the Control phase and 7 days [2-24] in the Intervention phase (P=0.7). When taking into account the competition between mortality and weaning from mechanical ventilation, we found no significant difference between the 2 phases (Gray test, P=0.4). The time-series analysis showed no difference for the duration of mechanical ventilation in the Intervention phase (P=0.6). Eighteen (20.7%) patients died in the Control phase, and 18 (18%) in the Intervention phase (P=0.6).. Scale-based lightening of continuous sedation-analgesia with repeated short general anesthesia for dressing is feasible in severe burn patients but failed to demonstrate a decrease in the duration of invasive mechanical ventilation.

Topics: Adult; Analgesics, Opioid; Burns; Clinical Protocols; Controlled Before-After Studies; Dose-Response Relationship, Drug; Feasibility Studies; Female; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Ketamine; Male; Midazolam; Middle Aged; Nurses; Oxycodone; Pain; Pain Management; Pain Measurement; Pain, Procedural; Pregabalin; Remifentanil; Respiration, Artificial; Time Factors; Ventilator Weaning

The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients.. We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012.. The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12-1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03-1.27), and hospitalization (HR 1.33, 95% CI 1.31-1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16-1.28) and hospitalization (HR 1.37, 95% CI 1.33-1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95-1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation.. Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.

Topics: Adult; Aged; Analgesics, Opioid; Cause of Death; Drug Prescriptions; Female; Gabapentin; Hospitalization; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pain; Polypharmacy; Pregabalin; Registries; Renal Dialysis; Retrospective Studies; Risk Assessment; United States; Young Adult

Prenatal antiepileptic drug exposure could demonstrate both congenital malformations and behavioral impairments in offspring.. This study was performed to assess the effects of prenatal exposure to pregabalin (PGB) on pain response, anxiety, motor activity and some behavior of adult offspring rats.. Pregnant Wistar rats received PGB (7.5, 15 and 30 mg/kg/ip) during embryonic days 9.5- 15.5. The pain response, anxiety-like behaviors, locomotor activity, motor balance and coordination and anhedonia of adult offspring were examined by tail-flick and hot plate test, open field test, elevated plus maze (EPM), beam balance test and sucrose preference test in their 60th day of life, respectively.. Prenatal exposure to PGB revealed significant dose-dependent reduction in pain sensitivity (increase in pain latency response) in the hot plate test, especially in females, while anxiety-like behavior assessed in EPM and open field significantly reduced in males. In the open field, locomotor activity reduced significantly after exposure to PGB 30 mg/kg and motor coordination decreased dose-dependently, especially in males. Anhedonia, as an indication of sucrose preference or pleasure response, was not changed.. These findings suggest that prenatal PGB exposure could be associated with significant changes in pain response, anxiety, locomotor activity and coordination in adult offspring rats.

Topics: Anhedonia; Animals; Anticonvulsants; Anxiety; Behavior, Animal; Dose-Response Relationship, Drug; Female; Locomotion; Male; Pain; Pregabalin; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sucrose

Two Persian breed cats, 10 and 5 years of age, were presented separately for difficulty prehending food as well as behavioral abnormalities including interanimal aggression and restlessness, pacing, or compulsive overgrooming. Both cats would regularly rest their head and neck in an extended position. Neurologic examination demonstrated calvarial and craniocervical junction pain in both and an L4-S3 myelopathy in one. Brain MRI of both cases, and CT and necropsy in 1 case, demonstrated ventriculomegaly and caudal fossa crowding, cerebellar indentation, and foramen magnum herniation consistent with Chiari-like malformation. No syringomyelia was present in either cat. The 2 cats were treated with anti-inflammatory doses of prednisolone with little to no clinical response, but experienced improvement with pregabalin and omeprazole. The 2 cats' clinical signs were consequently attributed to neuropathic and posture-related pain secondary to Chiari-like malformation. Persian breed cats may have a predisposition to Chiari-like malformation, which may not be solely a morphometric variant, and symptomatic cats may present with manifestations of neuropathic pain different from the classic signs reported in dogs.

Topics: Aggression; Animals; Anxiety; Arnold-Chiari Malformation; Brain; Cat Diseases; Cats; Craniosynostoses; Feeding Behavior; Female; Magnetic Resonance Imaging; Male; Omeprazole; Pain; Pregabalin

Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline.. An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options.. One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time.. There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.

Topics: Acetaminophen; Advance Care Planning; Amitriptyline; Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Breakthrough Pain; Calciphylaxis; Gabapentin; Humans; Kidney Failure, Chronic; Nephrology; Pain; Pain Management; Pain, Procedural; Palliative Medicine; Practice Patterns, Physicians'; Pregabalin; Referral and Consultation; Surveys and Questionnaires; United Kingdom

Topics: Acetaminophen; Analgesics; Analgesics, Opioid; Celecoxib; Drug Combinations; Drug Prescriptions; General Surgery; Humans; Opioid-Related Disorders; Pain; Practice Patterns, Physicians'; Pregabalin

Topics: Analgesics; Chronic Pain; Drug Misuse; Gabapentin; Humans; Pain; Practice Guidelines as Topic; Pregabalin

Streptozotocin (STZ) is commonly used to induce diabetes mellitus in experimental animal studies on peripheral diabetic neuropathy (PDN). Animals with STZ model of diabetes commonly develop changes in test stimulus-evoked pain behavior. However, it is still unclear whether rats with STZ model of diabetes have ongoing pain. Here we assessed whether STZ-induced diabetes induces ongoing pain-like behavior in male rats using conditioned place-preference (CPP) paradigm. CPP was tested in the fourth week of diabetes by pairing one chamber of the CPP device with vehicle and another chamber with either pregabalin (an established analgesic; 30 mg/kg i.p.; n = 9) or Chembridge-5861528 (a TRPA1 channel antagonist; 30 mg/kg i.p.; n = 9). After drug-pairings, the animals were allowed to choose which chamber they preferred. Mechanical sensitivity was assessed with monofilaments and chemonociception in the skin by determining mustard oil-induced pain behavior. Diabetic animals developed in two weeks mechanical hypersensitivity that changed into hyposensitivity by the fourth week. Mustard oil-induced sustained pain was reduced by the 4

Topics: Analgesics; Animals; Conditioning, Psychological; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Male; Mustard Plant; Pain; Plant Oils; Pregabalin; Rats; Rats, Wistar; Streptozocin; TRPA1 Cation Channel

Topics: Analgesics, Opioid; Humans; Hyperalgesia; Laparoscopy; Nephrectomy; Pain; Pregabalin

Topics: Analgesics, Opioid; Humans; Hyperalgesia; Laparoscopy; Nephrectomy; Pain; Pregabalin

The creation of a new valid preclinical model of articular pain by the intra-articular (i.a.) injection of mucilages for the screening of new treatments against arthritis.. A single intra-articular injection (20 μl) of mucilages (from Althaea officinalis roots and Linum usitatissimun seeds) or vegetal components (Amorphophallus konjac gum powder and β-glucan, used as reference standard) were assessed in the rat. The pathology progression was monitored by behavioural measurements (paw pressure test, von Frey test, incapacitance test and beam balance test) and compared to that induced by the i.a. injections of monoiodioacetate (MIA) and Complete Freund's Adjuvant (CFA), well-recognized models of osteoarthritis and rheumatoid arthritis, respectively.. Among all, the mucilage of L. usitatissimun showed the best pro-algic profile inducing a painful long-lasting condition. Hypersensitivity was characterized as a mixed form of inflammatory and neuropathic pain by the responsiveness to ibuprofen (100 mg/kg, p.o.) and pregabalin (30 mg/kg, p.o.). The histological evaluation of joint showed a damage that represents both MIA and CFA features.. In conclusion, a single i.a. injection of L. usitatissimun mucilage can represent a valid model to assess articular pain in the rat for the screening of new treatments against arthritis.

Topics: Althaea; Analgesics; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Flax; Freund's Adjuvant; Ibuprofen; Injections, Intra-Articular; Male; Neuralgia; Osteoarthritis; Pain; Plant Mucilage; Pregabalin; Rats; Rats, Sprague-Dawley

Although reproducibility is considered essential for any method used in scientific research, it is investigated only rarely; thus, strikingly little has been published regarding the reproducibility of evoked pain models involving human subjects. Here, we studied the reproducibility of a battery of evoked pain models for demonstrating the analgesic effects of two analgesic compounds.. A total of 81 healthy subjects participated in four studies involving a battery of evoked pain tests in which mechanical, thermal and electrical stimuli were used to measure pain detection and tolerance thresholds. Pharmacodynamic outcome variables were analysed using a mixed model analysis of variance, and a coefficient of variation was calculated by dividing the standard deviation by the least squares means.. A total of 76 subjects completed the studies. After being administered pregabalin, the subjects' pain tolerance thresholds in the cold pressor and pressure stimulation tests were significantly increased compared to the placebo group. Moreover, the heat pain detection threshold in UVB-irradiated skin was significantly increased in subjects who were administered ibuprofen compared to the placebo group. Variation among all evoked pain tests ranged from 2.2% to 30.6%.. Four studies using a similar design showed reproducibility with respect to the included evoked pain models. The relatively high consistency and reproducibility of two analgesics at doses known to be effective in treating clinically relevant pain supports the validity of using this pain test battery to investigate the analgesic activity and determine the active dosage of putative analgesic compounds in early clinical development.. The consistency and reproducibility of measuring the profile of an analgesic at clinically relevant doses illustrates that this pain test battery is a valid tool for demonstrating the analgesic activity of a test compound and for determining the optimal active dose in early clinical drug development.

Topics: Adult; Analgesics; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Pregabalin; Reproducibility of Results; Skin

Topics: Accidental Falls; Adolescent; Child; Gabapentin; Humans; Pain; Pregabalin

Topics: Central Nervous System Sensitization; Humans; Osteoarthritis; Pain; Pregabalin; Tapentadol

The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behaviour (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non-affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components.

Topics: Analgesics; Animals; Female; Neuropeptides; Osteoarthritis; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley

Treatment challenges necessitate new approaches to customize care to individual patient needs. Integrating data from randomized controlled trials and observational studies may reduce potential covariate biases, yielding information to improve treatment outcomes. The objective of this study was to predict pregabalin responses, in individuals with painful diabetic peripheral neuropathy, by examining time series data (lagged inputs) collected after treatment initiation vs. baseline using microsimulation.. The platform simulated pregabalin-treated patients to estimate hypothetical future pain responses over 6 weeks based on six distinct time series regressions with lagged variables as inputs (hereafter termed "time series regressions"). Data were from three randomized controlled trials (N = 398) and an observational study (N = 3159). Regressions were derived after performing a hierarchical cluster analysis with a matched patient dataset from coarsened exact matching. Regressions were validated using unmatched (observational study vs. randomized controlled trial) patients. Predictive implications (of 6-week outcomes) were compared using only baseline vs. 1- to 2-week prior data.. Time series regressions for pain performed well (adjusted R. Effective prediction of pregabalin response for painful diabetic peripheral neuropathy was accomplished through combining cluster analyses, coarsened exact matching, and time series regressions, reflecting distinct patterns of baseline and "on-treatment" variables. These results advance the understanding of microsimulation to predict patient treatment responses through integration and inter-relationships of multiple, complex, and time-dependent characteristics.. WHY COMBINE DIFFERENT DATA SOURCES?: Analyzing the tremendous amount of patient data can provide meaningful insights to improve healthcare quality. Using statistical methods to combine data from clinical trials with real-world studies can improve overall data quality (e.g., reducing biases related to real-world patient variability). WHY CONSIDER A TIME SERIES ANALYSIS?: The best predictor of future outcomes is past outcomes. A “time series” collects data at regular intervals over time. Statistical analyses of time series data allow us to discern time-dependent patterns to predict future clinical outcomes. Modeling and simulation make it possible to combine enormous amounts of data from clinical trial databases to predict a patient’s clinical response based on data from similar patients. This approach improves selecting the right drug/dose for the right patient at the right time (i.e., personalized medicine). Using modeling and simulation, we predicted which patients would show a positive response to pregabalin (a neuropathic pain drug) for painful diabetic peripheral neuropathy. WHAT ARE THE MAJOR FINDINGS AND IMPLICATIONS?: For pregabalin-treated patients, a time series analysis had substantially more predictive value vs. analysis only of baseline data (i.e., data collected at treatment initiation). The ability to best predict which patients will respond to therapy has the overall implication of better informing drug treatment decisions. For example, an appropriate modeling and simulation platform complete with relevant historical clinical data could be integrated into a stand-alone device used to monitor and also predict a patient’s response to therapy based on daily outcome measures (e.g., smartphone apps, wearable technologies).

Topics: Aged; Analgesics; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Amides; Analgesics; Animals; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic Nucleotide Phosphodiesterases, Type 7; Hyperalgesia; Male; Mice; Molecular Docking Simulation; Pain; Pain Measurement; Peripheral Nervous System Diseases; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Rats, Wistar; TRPA1 Cation Channel

We aimed to evaluate the incidence of (and risk factors for) postoperative pregabalin and/or limaprost to treat persistent numbness and/or pain of the lower extremities after lumbar spinal stenosis (LSS) surgery.. Medical records of 329 patients (168 men, 161 women; average age 70 years) were retrospectively reviewed for data on the duration of LSS diagnosis; LSS disease; preoperative medication (limaprost, pregabalin, or combined limaprost/pregabalin; duration); symptoms; preoperative/postoperative intermittent claudication (IC); operation type; and postoperative medication and period.. Limaprost, pregabalin, and combined limaprost/pregabalin were prescribed preoperatively for 43%, 7%, and 5% of patients, respectively. At an average of 21 months postoperatively, limaprost, pregabalin, and combined therapy were prescribed in 11%, 8%, 4% of patients, respectively. Medication requirement was significantly lower postoperatively than preoperatively (P < 0.0001). Significant risk factors for required postoperative medication were required preoperative medication (odds ratio [OR] 3.088, 95% confidence interval [CI] 1.679 to 5.681]; postoperative period (OR 1.063, 95% CI 1.031 to 1.096); and postoperative IC (OR 3.868, 95% CI 1.481 to 10.103). A negative impact from postoperative medication was seen in patients who had undergone decompression surgery (OR 0.589, 95% CI 0.377 to 0.918).. Overall, 23% of LSS patients required medication for pain and/or numbness at 21 months postoperatively. Significant factors portending required postoperative medication were preoperative medication, longer postoperative period, and postoperative IC. A negative influence from postoperative medication was seen in patients who had undergone decompression surgery without fusion.

Topics: Aged; Alprostadil; Decompression, Surgical; Female; Humans; Hypesthesia; Lumbar Vertebrae; Male; Middle Aged; Pain; Postoperative Period; Pregabalin; Retrospective Studies; Spinal Stenosis

Topics: Alprostadil; Analgesics; Humans; Pain; Pregabalin; Spinal Stenosis

Many patients with opioid use disorder report symptoms similar to restless legs syndrome (RLS) during withdrawal. However, whether these symptoms are true RLS, their predictors and effect of treatment with pregabalin are still unknown.. A total of 19 consecutive patients with opioid use disorder who were admitted for detoxification were included in this study after obtaining informed consent. Information regarding addiction was noted, and they were screened for RLS every morning and evening. Patients were also asked to provide information regarding their sleep quality during the previous night. To control opioid withdrawal, they were prescribed buprenorphine. Pregabalin was prescribed to patients who developed RLS. For analysis, patients were divided in two groups: those with RLS and those without RLS.. The average age of the subjects included in this study was 30.2 (±10.4) years. Mean duration of substance abuse was 56.8 (±38.4) months. Ten patients developed symptoms of RLS. Groups with RLS and without RLS were comparable with reference to demographics, laboratory parameters, and dose of buprenorphine that was required to control withdrawal symptoms. On average, RLS appeared after 1.7 days of abstinence. Patients described their symptoms such as crawling, creeping sensation in the muscles or "just pain". Eight out of 10 subjects reported symptoms limited to legs; however, two described similar problems in their upper limbs as well. A change in sleep pattern was observed with delayed sleep onset at night, delayed wake time in the morning, and spending a major proportion of day asleep. Pregabalin brought significant relief to the symptoms of RLS and sleep quality.. RLS during opioid withdrawal was an independent illness seen in half of the patients. It appeared to be mediated through mu-receptors, with contributions from other factors. Pregabalin improved symptoms of RLS and quality of sleep in these patients.

Topics: Adult; Analgesics; Buprenorphine; Female; Humans; Male; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pregabalin; Restless Legs Syndrome; Sleep; Substance Withdrawal Syndrome

The objective is using saliva instead of plasma for pregabalin therapeutic drug monitoring (TDM) since saliva reflects the free non-protein bound drug concentration, simple and noninvasive sampling, cheaper and does not require the expertise of drawing blood. Forty four patients participated in this study, two samples of saliva and another two of blood were taken from each patient; first sample of both saliva and blood is the trough sample and was taken just before the first dose of the day and second sample is the peak sample and was taken 1 h after taking the first dose of the day. Descriptive statistics and t-testing after log transformation were done using Excel, p-value=0.05 was adopted for significant difference. Optimized effective intestinal permeability of pregabalin was estimated by PK-Sim program version 7. This study for the first time revealed that pregabalin is excreted in saliva and classified as class 1 based on Salivary Excretion Classification System (SECS). A good correlation of 0.71-0.83 between Cmin and Cmax of plasma and saliva pregabalin was observed respectively which indicate that saliva sampling is a good alternative matrix for pregabalin TDM. C/D-ratios were calculated to demonstrate pharmacokinetic variability of Pregabalin; the results showed that C/D-ratio was higher in women, elderly and in those patients who had Scr.≥0.9 mg/dl. Proposed pregabalin therapeutic ranges are 0.7 to 1.84 µg/ml in plasma and 0.055 to 0.145 µg/ml in saliva, for neuropathic pain, diabetic neuropathy and disc prolapse patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Biological Variation, Population; Drug Monitoring; Female; Humans; Intestinal Mucosa; Jordan; Male; Middle Aged; Pain; Permeability; Pregabalin; Saliva; Salivary Elimination; Sex Factors; Young Adult

Prior work applied hierarchical clustering, coarsened exact matching (CEM), time series regressions with lagged variables as inputs, and microsimulation to data from three randomized clinical trials (RCTs) and a large German observational study (OS) to predict pregabalin pain reduction outcomes for patients with painful diabetic peripheral neuropathy. Here, data were added from six RCTs to reduce covariate bias of the same OS and improve accuracy and/or increase the variety of patients for pain response prediction. Using hierarchical cluster analysis and CEM, a matched dataset was created from the OS (N = 2642) and nine total RCTs (N = 1320). Using a maximum likelihood method, we estimated weekly pain scores for pregabalin-treated patients for each cluster (matched dataset); the models were validated with RCT data that did not match with OS data. We predicted novel 'virtual' patient pain scores over time using simulations including instance-based machine learning techniques to assign novel patients to a cluster, then applying cluster-specific regressions to predict pain response trajectories. Six clusters were identified according to baseline variables (gender, age, insulin use, body mass index, depression history, pregabalin monotherapy, prior gabapentin, pain score, and pain-related sleep interference score). CEM yielded 1766 patients (matched dataset) having lower covariate imbalances. Regression models for pain performed well (adjusted R-squared 0.90-0.93; root mean square errors 0.41-0.48). Simulations showed positive predictive values for achieving >50% and >30% change-from-baseline pain score improvements (range 68.6-83.8% and 86.5-93.9%, respectively). Using more RCTs (nine vs. the earlier three) enabled matching of 46.7% more patients in the OS dataset, with substantially reduced global imbalance vs. not matching. This larger RCT pool covered 66.8% of possible patient characteristic combinations (vs. 25.0% with three original RCTs) and made prediction possible for a broader spectrum of patients. Trial Registration: www.clinicaltrials.gov (as applicable): NCT00156078, NCT00159679, NCT00143156, NCT00553475.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Biomarkers; Cluster Analysis; Computer Simulation; Diabetic Neuropathies; Double-Blind Method; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Interrupted Time Series Analysis; Male; Middle Aged; Neuralgia; Pain; Pain Measurement; Predictive Value of Tests; Pregabalin; Treatment Outcome

Topics: Aldehydes; Animals; Female; Fever; Inflammation; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Pain; Pregabalin; Saccharomyces cerevisiae

Topics: Aged; Calcineurin Inhibitors; Combined Modality Therapy; Cyclosporine; Drug Monitoring; Drug Therapy, Combination; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hip; Humans; Lower Extremity; Male; Myelodysplastic Syndromes; Pain; Pregabalin; Severity of Illness Index; Tacrolimus; Transplantation, Homologous; Treatment Outcome

Topics: Humans; Pain; Pain Measurement; Pregabalin; Quality of Life; Sciatica

Topics: Aged; Comorbidity; Diclofenac; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Fentanyl; Humans; Pain; Pregabalin

Pregabalin, widely used in the treatment of several pain disorders, is usually well tolerated. Uncommonly, the drug may induce cardiac side effects, rarely prolongation of the PR interval. The latter has never been described in patients with healthy heart or normal renal function. We characterize a unique case of a young man with extrapulmonary tuberculosis and no detectable or known cardiac or kidney diseases, treated with pregabalin to control the severe pain due to the involvement of the spinal cord by the tuberculosis, showing an atrioventricular (AV) block due to pregabalin administration. The reported case emphasizes the need of monitoring PR interval during treatment with pregabalin, even in patients without background of cardiac or renal diseases.

Topics: Atrioventricular Block; Calcium Channel Blockers; Electrocardiography; Humans; Male; Pain; Pregabalin; Treatment Outcome; Tuberculosis, Central Nervous System; Young Adult

To evaluate pregabalin effects on glycemic (hemoglobin A1c [HbA1c] and glucose) and lipid (low- and high-density lipoprotein [LDL and HDL, respectively], and total cholesterol, and triglycerides) control in patients with painful diabetic peripheral neuropathy (pDPN).. Data from 11 randomized, double-blind trials were pooled to assess change-from-baseline treatment differences (pregabalin or placebo) in glycemic and lipid parameters using analysis of covariance.. Patients received pregabalin doses (mg/d) of 150 (n=176), 300 (n=559), 600 (n=705), 150-600 (flexible dose, n=521), or placebo (n=1050). Statistically significant mean [95% confidence interval] within-treatment (pregabalin) changes occurred in HDL (600mg/d: -1.61mg/dl [-3.17, -0.05]), total cholesterol (flexible dose: -6.03mg/dl [-11.68, -0.39]), and triglycerides (flexible dose: +15.39mg/dl [1.56, 29.23]). Statistically significant differences from placebo were found in HbA1c (300mg/d: +0.11% [0.01, 0.21]) and HDL cholesterol (300mg/d: -1.78mg/dl [-3.36, -0.19], 600mg/d: -2.53mg/dl [-4.49, -0.57]). No within- or between-treatment changes were large enough to be clinically meaningful.. No apparent clinically meaningful effects of pregabalin on glycemic/lipid control were found in patients with pDPN.

Topics: Adult; Analgesics; Blood Glucose; Cholesterol; Diabetic Nephropathies; Dose-Response Relationship, Drug; Double-Blind Method; Glycated Hemoglobin; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Pain; Peripheral Nervous System Diseases; Pregabalin; Randomized Controlled Trials as Topic; Reproducibility of Results; Triglycerides

Topics: Analgesics; Fibromyalgia; Humans; Pain; Pregabalin

Topics: Analgesics; Fibromyalgia; Humans; Pain; Pregabalin

A novel series of sigma (σ) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective σ1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as σ1 ligands for antinociception is warranted. This study supports the notion that selective σ1 antagonism could be a useful strategy in the development of novel antipain therapy.

Topics: Analgesics; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Formaldehyde; Injections, Intraperitoneal; Isoxazoles; Ligands; Mice; Mice, Inbred Strains; Molecular Structure; Pain; Receptors, sigma; Sigma-1 Receptor; Structure-Activity Relationship

Gabapentinoids are effective adjunct drugs for reducing postoperative pain. However, the effects of gabapentinoids on wound healing have not been evaluated yet. In this study we evaluated their effects on wound healing. A total of 17 male Wistar-Albino rats, 250-350 g, were divided into three groups randomly: control group (n = 5, 2 ml saline), gabapentin group (n = 6, 20 mg/kg gabapentin) and pregabalin group (n = 6, 20 mg/kg pregabalin). Until day 13 inflammation scores were significantly lower (P < 0·05) and wound healing was significantly better in the control group when compared with gabapentin and pregabalin groups (P < 0·001). Inflammation scores were significantly lower in pregabalin group when compared with gabapentin group until day 13. But wound healing was significantly better in gabapentin group than in pregabalin group between days 13 and 21. In conclusion when gabapentin and pregabalin were compared, although pregabalin decreases inflammation scores, gabapentin has better results in wound healing.

Topics: Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Pain; Pregabalin; Rats; Rats, Wistar; Treatment Outcome; Wound Healing

Oxycodone is increasingly being used in combination with pregabalin. Pregabalin use is prevalent in opioid-dependent individuals. A high number of deaths caused by the co-use of gabapentinoids and opioids occur. It is not known whether pregabalin affects concentrations of oxycodone or morphine in the central nervous system.. Effects of pregabalin on acute oxycodone or morphine-induced antinociception, tolerance and sedation were studied using tail-flick, hot plate and rotarod tests in male Sprague-Dawley rats. Concentrations of pregabalin, opioids and their major metabolites in the brain were quantified by mass spectrometry.. In the hot plate test, morphine (2.5 mg/kg, s.c.) caused antinociception of 28% maximum possible effect (MPE), whereas pregabalin (50 mg/kg, i.p.) produced 8-10% MPE. Co-administration of pregabalin and morphine resulted in antinociception of 63% MPE. Oxycodone (0.6 mg/kg s.c.) produced antinociception of 18% MPE, which increased to 39% MPE after co-administration with pregabalin. When pregabalin 10 mg/kg was administered before oxycodone (0.6 mg/kg, s.c.) or morphine (2.5 mg/kg), only the effect of oxycodone was potentiated in the tail-flick and the hot plate tests. Brain concentrations of the opioids, their major metabolites and pregabalin were unchanged. Pregabalin co-administration (50 mg/kg, i.p., once daily) did not prevent the development of morphine tolerance.. Pregabalin potentiated antinociceptive and sedative effects of oxycodone and morphine in acute nociception. Co-administration of pregabalin with the opioids did not affect the brain concentrations of oxycodone or morphine. Pregabalin did not prevent morphine tolerance.

Topics: Analgesics, Opioid; Animals; Drug Interactions; Drug Therapy, Combination; Hot Temperature; Male; Morphine; Nociception; Oxycodone; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley

Topics: Analgesics; Cognition; Female; Humans; Male; Pain; Piperidines; Pregabalin; Respiration

Topics: Abnormalities, Drug-Induced; Calcium Channel Blockers; Female; Humans; Mental Disorders; Pain; Pregabalin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

Tacrolimus and cyclosporin are calcineurin inhibitors (CIs) commonly used in organ transplants. These agents rarely cause a severe, debilitating pain syndrome of especially lower extremities, known as CI pain syndrome (CIPS). Although the pathogenesis is not well understood, neuropathic pain mechanisms have started to be discussed in the recent literature. Here, presenting a 48-year-old male with CIPS who recovered after pregabalin 150 mg twice daily, we aimed to emphasize the importance of this syndrome and offer a new approach for the treatment. This is the first report in the literature where pregabalin is demonstrated to be effective in CIPS.

Topics: Analgesics; Calcineurin Inhibitors; Cyclosporine; Humans; Male; Middle Aged; Organ Transplantation; Pain; Pregabalin; Tacrolimus

We investigated the efficacy of pregabalin (PGB) for neuropathic leg pain in lumbar spinal stenosis (LSS) patients with disturbed activities of daily living (ADL)/quality of life (QOL) in a prospective observational study. Subjects were a total of 104 LSS patients with neuropathic pain (NeP) in leg and neurological intermittent claudication (IMC) refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) for at least a month. NeP was identified using screening tool, Pain DETECT questionnaire. Visual analog scale (VAS) scores and responses to the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were assessed before and 6 weeks after PGB treatment initiation. Changes in IMC distance and adverse events were also recorded. PGB significantly improved their VAS scores for pain and sleep quality (P < 0.001). With respect to JOABPEQ, significant improvements were observed with regard to the following dimensions: pain-related disorders (P < 0.01), lumbar spine dysfunction (P = 0.031), gait disturbance (P = 0.028), and psychological disorders (P = 0.014). The IMC distance showed an improvement tendency after PGB treatment, albeit with no significance (P = 0.063). Minor adverse events such as dizziness were observed. PGB can be effective for neuropathic leg pain refractory to NSAIDs in LSS patients, resulting in not only pain control but also improving lower back pain-related ADL/QOL scores.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Female; Humans; Japan; Leg; Male; Middle Aged; Pain; Pain Measurement; Pain Perception; Pregabalin; Prospective Studies; Spinal Stenosis; Young Adult

Complex regional pain syndrome (CRPS) is a painful and disabling disorder that usually affects the extremities. This complication may affect the knee joint after total knee arthroplasty (TKA). We report a unique case of CRPS of the foot and ankle, which was an unusual involvement site for CRPS after TKA.

Topics: Aged; Amitriptyline; Analgesics; Ankle; Arthroplasty, Replacement, Knee; Complex Regional Pain Syndromes; Female; Humans; Knee Joint; Magnetic Resonance Imaging; Pain; Postoperative Complications; Pregabalin

Topics: Analgesics; Drugs, Generic; England; gamma-Aminobutyric Acid; Humans; Legislation, Drug; Pain; Pain Management; Pregabalin

Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients' encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization.. Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/2012, and ≥12 months pre- and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims.. No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058).. The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Cohort Studies; Diabetic Neuropathies; Drug Interactions; Duloxetine Hydrochloride; Female; Humans; Male; Medicare Part C; Middle Aged; Pain; Pregabalin; Prescription Drugs; Prevalence; Retrospective Studies; United States; Young Adult

Topics: Analgesics; Drugs, Generic; Humans; Pain; Patents as Topic; Pregabalin; Primary Health Care

Topics: Analgesics; Cost-Benefit Analysis; Delivery of Health Care; Drug Industry; Drug Prescriptions; gamma-Aminobutyric Acid; Humans; Pain; Practice Patterns, Physicians'; Pregabalin; Quality of Health Care; United Kingdom

Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented.. A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits.. Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year.. In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes.

Topics: Analgesics; Costs and Cost Analysis; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pain; Pregabalin; Racial Groups; Retrospective Studies; United States; United States Department of Veterans Affairs; Veterans

Managed healthcare organizations often utilize formulary management strategies such as prior authorization and step therapy to guide appropriate medication use and to control medication expenditures. The objective of this study was to examine clinical and economic outcomes associated with implementation of a pregabalin step therapy (ST) policy among Medicare Advantage Prescription Drug (MAPD) members.. Pharmacy and medical claims data from Humana (restricted cohort; ST policy implemented 01/01/2009) and Thomson Reuters MarketScan(®) (unrestricted cohort) were analyzed for MAPD members aged 65 to 89 years receiving treatment for painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN) or fibromyalgia (FM). Difference-in-differences (DID) was used to examine year-over-year changes in disease-related and all-cause utilization and costs. Regression analyses examined medication utilization and healthcare expenditures after controlling for between-group compositional differences.. We identified 13,911 members in the restricted cohort and matched to members from unrestricted health plans. FM (51.0%) and pDPN (41.8%) were the most common diagnoses. Members in the unrestricted cohort were older and had a greater level of comorbidity than members in the restricted cohort. The restricted cohort demonstrated greater year-over-year decrease in pregabalin utilization and increase in year-over-year gabapentin utilization compared with the unrestricted cohort. ST restriction was associated with an increase in disease-related pharmacy costs and a decrease in total medical costs for the restricted cohort compared with the unrestricted cohort. There was no difference between cohorts in total healthcare cost.. After controlling for differences in age and comorbidity burden between the groups, implementation of a pregabalin ST restriction was associated with increased disease-related pharmacy costs and decreased total medical costs; however, there was no net difference in total healthcare cost or total pharmacy cost.

Topics: Aged; Aged, 80 and over; Analgesics; Cohort Studies; Drug Administration Schedule; Drug Utilization Review; Female; gamma-Aminobutyric Acid; Humans; Male; Medicare Part C; Pain; Pregabalin; Retrospective Studies; United States

To evaluate pharmacotherapeutic success in patients with painful traumatic trigeminal neuropathy (PTTN) and to identify patient or pain characteristics that may predict treatment outcome.. Pharmacotherapy was instituted for PTTN patients and was based on widely accepted protocols for neuropathic pain and conducted in an open fashion. Outcome was assessed by employing prospective diaries recording pain intensity measured with an 11-point (0 to 10) verbal pain score (VPS). Individual characteristics in the patients and their influence on outcome were analyzed. Treatment results in the PTTN patients were compared with those in classical trigeminal neuralgia (CTN) patients, who were used as a comparative cohort. Data were analyzed with a Pearson chi-square test for nominal variables and with an independent samples t test or analysis of variance for continuous variables.. A total of 145 patients were included: 91 with PTTN and 54 with CTN. In PTTN patients, 11% had a ≥ 50% reduction in pain intensity. Higher VPS scores in the PTTN patients were associated with a significantly reduced response to therapy (P = .03). No other pain-related or demographic parameters were associated with treatment outcome in the PTTN patients. Also the response rate of PTTN patients was significantly inferior to that of CTN patients, 74.1% of whom attained a significant reduction in pain intensity (P < .001).. This study underpins the poor pharmacotherapeutic prognosis of PTTN. The results support findings on neuropathic pain in other sites and point to the need for further research and reexamination of current PTTN treatment protocols.

Topics: Amines; Amitriptyline; Analgesics; Analgesics, Non-Narcotic; Baclofen; Carbamazepine; Clinical Protocols; Cohort Studies; Cyclohexanecarboxylic Acids; Drug Combinations; Duloxetine Hydrochloride; Female; Follow-Up Studies; GABA-B Receptor Agonists; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Medical Records; Middle Aged; Nortriptyline; Pain; Pain Measurement; Pregabalin; Prognosis; Prospective Studies; Thiophenes; Treatment Outcome; Trigeminal Nerve Injuries; Trigeminal Neuralgia

This study investigated the effects of Phα1β, pregabalin and diclofenac using an animal model of fibromyalgia (FM). Repeated administration of reserpine (0.25 mg/kg sc) once daily for three consecutive days significantly decreased thermal hyperalgesia, mechanical allodynia, and dopamine and serotonin content in the brain on the 4th day. Phα1β and pregabalin treatment completely reverted the mechanical allodynia and thermal hyperalgesia induced by reserpine treatment on the 4th day, but diclofenac was ineffective. Reserpine treatment significantly increased the immobility time in the forced swim test, which is indicative of depression in the animals. Phα1β, but not pregabalin, reduced the immobility time (56%), suggesting that Phα1β may control persistent pathological pain in FM.

Topics: Animals; Brain; Calcium Channel Blockers; Diclofenac; Disease Models, Animal; Dopamine; Fibromyalgia; gamma-Aminobutyric Acid; Hyperalgesia; Male; Mice; Pain; Pregabalin; Reserpine; Serotonin; Spider Venoms; Spiders

We provide a template for finding target allocation proportions in optimal allocation designs where the target will be invariant for both shifts in location and scale of the response distributions. One possible application of such target allocation proportions is to carry out a response-adaptive allocation. While most of the existing designs are invariant for any change in scale of the underlying distributions, they are not location invariant in most of the cases. First, we indicate this serious flaw in the existing literature and illustrate how this lack of location invariance makes the performance of the designs very poor in terms of allocation for any drastic change in location, such as the changes from degrees centigrade to degrees Fahrenheit. We illustrate that unless a target allocation is location invariant, it might lead to a completely irrelevant and useless target for allocation. Then we discuss how such location invariance can be achieved for general continuous responses. We illustrate the proposed method using some real clinical trial data. We also indicate the possible extension of the procedure for more than two treatments at hand and in the presence of covariates.

Topics: Computer Simulation; gamma-Aminobutyric Acid; Humans; Models, Statistical; Neuralgia, Postherpetic; Pain; Pregabalin; Research Design

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected.

Topics: alpha-MSH; Analgesics; Animals; Apomorphine; Carrageenan; Dopamine Agonists; Female; gamma-Aminobutyric Acid; Libido; Male; Mice; Motivation; Pain; Peptides, Cyclic; Pregabalin; Sex Factors; Sexual Behavior, Animal; Zymosan

Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.

Topics: Adult; Antipruritics; Child, Preschool; DNA Mutational Analysis; Female; gamma-Aminobutyric Acid; Humans; Male; Mutation; NAV1.7 Voltage-Gated Sodium Channel; Pain; Pain Threshold; Physical Stimulation; Pregabalin; Pruritus; Treatment Outcome

The present study investigates the effects of pregabalin (PGB), acetaminophen (ACET) and tenoxicam (TNX) administration in somatic and visceral nociception, using the tail flick test and the writhing test in mice.. In the tail flick test, the substances were administered orally and the latency time response was recorded 15, 30, 60, 90 and 120 min after administration. In the writhing test, pain responses were scored every 5 min during a 30-min period after intraperitoneal injection of diluted acetic acid.. Our study demonstrated that oral administration of the combination PGB-ACET resulted in a stronger increase of latency reaction - statistically significant after 15 min compared to TNX and after 30 min compared to PGB in tail flick test. In the writhing test, the combination PGB-ACET, but also PGB-TNX, resulted in a stronger decrease of writhe numbers - statistically significant compared to the effects of the separate administration of each substance. This decrease was more intense in animals treated with the combination PGB-ACET than with PGB-TNX.. These results suggest an antinociceptive activity which may be a consequence of the synergic action of the substances.

Topics: Acetaminophen; Acetic Acid; Analgesics; Animals; Drug Combinations; Drug Synergism; gamma-Aminobutyric Acid; Hot Temperature; Male; Mice; Pain; Piroxicam; Pregabalin

Although pregabalin has been shown to have preclinical and clinical efficacy in neuropathic pain, the mechanism of its antinociceptive action is still unknown in other pain states. This study aimed to evaluate the antinociceptive effect of pregabalin and its underlying spinal mechanisms related to mitogen activated protein kinases (MAPKs) in neuron and microglia following intraplantar injection of zymosan model. Zymosan evoked thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia starting from 1 h and persistent until 5 h post-injection, which were dose-dependently reversed by oral pretreatment of pregabalin (3, 10, and 30 mg/kg). Pregabalin dramatically inhibited zymosan-induced Fos expression (a marker for neuronal activation) and microglia activation (using markers CD11b and ED1) in the spinal dorsal horn. Moreover, zymosan significantly increased phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 (double labeling with neuron), ERK5 (double labelling with neuron and microglia) and p38 MAPK (double labeling with microglia) in the spinal dorsal horn, which overall elevations were reversed by pregabalin. These findings suggest that blockage of MAPKs activation in neuron and microglia might be closely related to the antinociceptive effect of pregabalin on zymosan-induced peripheral inflammatory pain.

Topics: Analgesics; Animals; Disease Models, Animal; gamma-Aminobutyric Acid; Male; Mitogen-Activated Protein Kinases; Pain; Pain Measurement; Phosphorylation; Pregabalin; Rats; Rats, Sprague-Dawley; Treatment Outcome; Zymosan

The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 μg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action.

Topics: Animals; Behavior, Animal; Calcium; Female; gamma-Aminobutyric Acid; Glutathione; Hyperalgesia; Lipid Peroxidation; Male; Oxidative Stress; Pain; Peripheral Nervous System Diseases; Phytotherapy; Plant Leaves; Plant Preparations; Pregabalin; Rats; Rats, Wistar; Sciatic Nerve; Thiobarbituric Acid Reactive Substances; Vernonia; Vincristine

The effects of maslinic acid (1), a pentacyclic triterpenoid obtained from Olea europaea, were studied in several tests for nociception in mice. Systemic administration of 1 reduced acetic acid-induced writhing, the inflammatory phase of formalin-induced pain, and capsaicin-induced mechanical allodynia. However, it did not induce motor incoordination in the rotarod test. The topical administration of 1 also reduced the inflammatory phase of the formalin test, indicating that at least some of its effects are mediated peripherally. The present results demonstrate for the first time that maslinic acid induces antinociceptive and antiallodynic effects.

Topics: Analgesics; Animals; Capsaicin; gamma-Aminobutyric Acid; Hyperalgesia; Inflammation; Mice; Molecular Structure; Olea; Pain; Pain Measurement; Pregabalin; Rotarod Performance Test; Time Factors; Triterpenes

Pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X₃ receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-NN-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 ∼ 700 nM) at the hP2X₃ receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13 h-n, dramatically improved the selectivity profiles of hP2X₃ when compared with mP2X₁ and hP2X₇ receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X₃ receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X₃ receptor antagonist with an IC50 of 60 nM at hP2X₃ and marginal antagonistic activities of 10 μM at mP2X₁ and hP2X₇. Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 μM 36j displaying 65% inhibition while 20 μM pregabalin, a clinically available drug, showed only 31% inhibition.

Topics: Animals; Dose-Response Relationship, Drug; Drug Design; Humans; Molecular Structure; Oocytes; Pain; Pyridoxal Phosphate; Receptors, Purinergic P2X3; Structure-Activity Relationship; Xenopus

A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis.. Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy.. The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy.. The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.

Topics: Adult; Analgesics; Electric Stimulation; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Pancreatitis, Chronic; Placebos; Precision Medicine; Pregabalin; Pressure; Sensitivity and Specificity; Support Vector Machine; Treatment Outcome

Topics: Adult; Analgesics; Female; gamma-Aminobutyric Acid; Humans; Pain; Paresthesia; Pregabalin; Pruritus; Scalp

Drug interactions are an important issue of efficacious and safe pharmacotherapy. Although the use of drug combinations carries the potential risk of enhanced toxicity, when carefully introduced it enables to optimize the therapy and achieve pharmacological effects at doses lower than those of single agents. In view of the development of novel analgesic compounds for the neuropathic pain treatment little is known about their influence on the efficacy of currently used analgesic drugs. Below we describe the preliminary evaluation of support vector machine in the regression mode (SVR) application for the prediction of maximal antiallodynic effect of a new derivative of dihydrofuran-2-one (LPP1) used in combination with pregabalin (PGB) in the streptozocin-induced neuropathic pain model in mice. Based on SVR the most effective doses of co-administered LPP1 (4mg/kg) and PGB (1mg/kg) were predicted to cause the paw withdrawal threshold at 6.7g in the von Frey test. In vivo for the same combination of doses the paw withdrawal was observed at 6.5g, which confirms good predictive properties of SVR.

Topics: 4-Butyrolactone; Algorithms; Analgesics; Animals; Computer Simulation; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Administration Schedule; Drug Combinations; Furans; gamma-Aminobutyric Acid; Hyperalgesia; Male; Mice; Pain; Pain Measurement; Pain Threshold; Piperazines; Pregabalin; Software; Streptozocin; Support Vector Machine; Time Factors

Topics: Diabetic Neuropathies; Duloxetine Hydrochloride; Female; gamma-Aminobutyric Acid; Humans; Male; Pain; Pregabalin; Thiophenes

Topics: Analgesics; gamma-Aminobutyric Acid; General Practice; Guideline Adherence; Humans; Inappropriate Prescribing; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Practice Guidelines as Topic; Pregabalin; Prisoners; United Kingdom

The Fibromyalgia Impact Questionnaire (FIQ) is a patient-reported outcome that evaluates the impact of fibromyalgia (FM) on daily life. This study evaluated the relationships between the functional status of FM patients, measured with the FIQ at baseline, and median time to a clinically relevant pain reduction.. Data were derived from two randomised, placebo-controlled trials that evaluated pregabalin 300, 450 and 600 mg/day for the treatment of FM. The Kaplan-Meier (nonparametric) method was applied to estimate median times to 'transient' and 'stable' events. The transient event was defined as a ≥ 27.9% improvement on an 11-point daily pain diary scale (0 = no pain, 10 = worst possible pain), and the stable event was defined as the mean of the daily improvements ≥ 27.9% relative to baseline over the subsequent study duration starting on the day of the transient event. A parametric model using time-to-event analysis was developed for evaluating the relationship between baseline FIQ score and the median time to these events.. Median time was longer among patients treated with placebo relative to pregabalin for the transient events (11-12 days vs. 5-7 days) and stable events (86 days vs. 13-29 days). A significant association was observed between baseline FIQ scores and median time to transient and stable events (p < 0.001). Median times to events were similar between the studies. For transient pain reduction events, median times ranged from 3.0 to 4.5 days for baseline FIQ scores of 10, and 9.1-9.6 days for FIQ scores of 100; for stable pain reduction events, the median time ranged from 11.0 to 13.0 days and from 27.0 to 28.5 days for baseline FIQ scores of 10 and 100 respectively.. Time to a clinically relevant reduction in pain was significantly associated with FM severity at baseline as measured by the FIQ. Such an analysis can inform patient and physician expectations in clinical practice.

Topics: Analgesics; Double-Blind Method; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Randomized Controlled Trials as Topic; Surveys and Questionnaires

To characterize and compare healthcare resource utilization and costs among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or gabapentin in a real-world clinical setting.. Retrospective cohort analysis using the MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases (2007-2009).. Patients with new prescriptions for pregabalin or gabapentin (index event) in 2008 and ≥1 healthcare encounter with an ICD-9 code for pDPN (250.6 or 357.2) within 30 days prior to the first prescription were identified and propensity score matched; continuous enrollment 12 months pre- and post-index was required. Pre- to post-index changes in 12-month all-cause and pDPN-attributable resource utilization and costs were compared between pregabalin and gabapentin using a difference-in-difference (DID) approach.. A total of 910 pregabalin patients (48.6% female; mean age 63.3 ± 12.1 years) were matched with 910 gabapentin patients (48.8% female; mean age 63.3 ± 12.1 years). The DID showed no significant differences between cohorts for pre- to post-index changes in any of the all-cause resource utilization categories. While prescription costs increased significantly more with pregabalin (DID -$563; p < 0.0001), the DID of $1603 for total healthcare costs per patient indicated that the pre- to post-index increases of $3081 for pregabalin and $4684 for gabapentin patients were comparable (p = 0.8474). Total pDPN-attributable healthcare costs were significantly higher with pregabalin (DID -$385; p < 0.0001), resulting from higher prescription costs (DID -$432; p < 0.0001). Limitations of this study include the inability to specifically link pDPN with medication prescribing; differences between groups despite propensity score matching; use of proxy measures for adherence parameters; and inability to capture efficacy outcomes.. Among patients initiating pregabalin or gabapentin, there were no significant differences between the drugs in the pre- to post-index changes in all-cause total healthcare costs, despite the increase in prescription costs for pregabalin.

Topics: Aged; Amines; Analgesics; Cyclohexanecarboxylic Acids; Databases, Factual; Diabetic Nephropathies; Female; Gabapentin; gamma-Aminobutyric Acid; Health Resources; Humans; Male; Middle Aged; Pain; Pregabalin; Prescription Fees; Retrospective Studies; United States

The aim of present study was to investigate the antinociceptive effect of pregabalin and tramadol either alone and or in combination on acute model of pain.. The antinociceptive effect of intraperitoneal administration of pregabalin (1 to 400 mg/kg) and tramadol (10 to 80 mg/kg) or combination of them were measured after 30 and 60 min on hot-plate in terms of maximum possible effect (%MPE) in mice.. Antinociceptive effect rose significantly for both pregabalin at doses 200 and 400 mg/kg and tramadol from 20 to 80 mg/kg in dose dependent manner. From linear equation the doses that increased antinociceptive effect by 50% (ED(50)) were 69 ± 8.2 mg/kg for tramadol and 246 ± 24 mg/kg for pregabalin. Unlike pregabalin, %MPE(30) (at 30(th) min) of tramadol was significantly higher than its %MPE(60). The interaction after co-administration of non analgesic dose of 10 mg/kg of pregabalin with low analgesic dose of 30 mg/kg of tramadol resulted super-additive and %MPE(30) and %MPE(60) were increased compared to each drug alone. In all other combination groups, the interaction were sub-additive particularly when non analgesic doses of each drug (10 mg/kg) were co-administrated and %MPE was decreased significantly compared to that of each drug alone.. Pregabalin revealed a comparative antinociceptive effect as similar to tramadol in acute model of pain, but interaction between these two drugs depends highly on their proportion in the combination. The analgesia may increase but adverse effects such as seizurogenic effect of tramadol can be reduced in clinical setting if right proportion is used. More studies are required to understand the mechanisms and clinical implication of such combinations.

Topics: Acute Pain; Analgesics; Analgesics, Opioid; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Drug Therapy, Combination; gamma-Aminobutyric Acid; Injections, Intraperitoneal; Male; Mice; Pain; Pregabalin; Time Factors; Tramadol

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Analgesics; Animals; Animals, Newborn; Biophysical Phenomena; Biophysics; Dopamine; Dopamine Agonists; Dose-Response Relationship, Drug; Electric Stimulation; gamma-Aminobutyric Acid; Hyperalgesia; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Fibers, Unmyelinated; Pain; Pain Threshold; Pregabalin; Reaction Time; Receptors, Dopamine D3; Reflex; Spinal Cord; Spinal Nerve Roots; Time Factors

A potent series of substituted (2S,4S)-benzylproline α(2)δ ligands have been designed from the readily available starting material (2S,4R)-hydroxy-L-proline. The ligands have improved pharmacokinetic profile over the (4S)-phenoxyproline derivatives described previously and have potential for development as oral agents for the treatment of neuropathic pain. Compound 16 has been progressed to clinical development.

Topics: Animals; Drug Design; Humans; Inhibitory Concentration 50; Ligands; Molecular Structure; Pain; Proline; Rats; Swine

It was previously shown that morphine more potently reduces the affective as compared to the sensory component of nociception, and this effect is independent of morphine's rewarding properties. Here we investigated whether this finding can be generalized to other classes of anti-nociceptive drugs. The effect of oxycodone (0-10 mg/kg, i.p.), tramadol (0-10 mg/kg, i.p.), ibuprofen (0-300 mg/kg, i.p.) and pregabalin (0-31.6 mg/kg, i.p.) on negative affect and mechanical hypersensitivity accompanying carrageenan-induced (0.5% intraplantar) inflammatory nociception was assessed using conditioned place aversion (CPA) and Randall Selitto paw pressure test, respectively. The rewarding effect of these drugs was assessed using conditioned place preference (CPP). All four anti-nociceptive drugs dose-dependently reduced carrageenan-induced CPA and mechanical hypersensitivity. Furthermore all drugs induced CPP, except for ibuprofen. Similar to morphine, oxycodone and tramadol showed a large dissociation of anti-aversive versus anti-nociceptive potency, i.e. 10 times more potent against the affective versus the sensory component of nociception. Oxycodone and tramadol were 30 and 10 times more potent to produce CPP in animals under normal versus painful conditions. Ibuprofen and pregabalin also showed a dissociation of anti-aversive and anti-nociceptive potency, but less pronounced (i.e. three times more potent against the affective component). However, pregabalin showed no dissociation between rewarding potency under normal versus painful conditions. Taken together, these data suggest that the dissociation of rewarding potency in animals under normal versus painful conditions is limited to drugs with an opioid mechanism of action, while the dissociation of anti-aversive and anti-nociceptive potency applies to anti-nociceptive drugs with different mechanisms of action.

Topics: Analgesics; Animals; Carrageenan; Conditioning, Psychological; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Ibuprofen; Inflammation; Male; Oxycodone; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley; Tramadol

The objective of the study was to conduct an analysis of pooled data from pregabalin fibromyalgia clinical trials to determine which fibromyalgia symptom and function domains drive patient perception of improvement.. Data from three double-blind, placebo-controlled trials of pregabalin in fibromyalgia patients were pooled for this analysis. Changes in independent variables, including the Medical Outcomes Study 36-item Short-Form Health Survey, Medical Outcomes Study-Sleep Scale, sleep quality score from the daily sleep diary, pain score from the daily pain diary, Fibromyalgia Impact Questionnaire, and Multidimensional Assessment of Fatigue were analyzed as predictors of outcome on the dependent variable, Patient Global Impression of Change (PGIC). Correlation analysis assessed relationships between the independent variables and PGIC. Cluster analysis identified dependencies among variables, and a shrinkage and selection method and stepwise logistic regression determined rank order of variables.. Improvement in PGIC at endpoint showed highest correlation with pain improvement, fatigue, sleep, and work and physical function (0.4 < r < 0.6). Cluster analysis identified three main clusters of symptoms at endpoint: mood (anxiety and depression), pain and sleep, and function and fatigue. Pain was ranked as the most important outcome explaining variability in PGIC, followed by fatigue and sleep.. Pain, fatigue, and sleep associate most strongly with improvement in PGIC. Physical- and work-related function also correlated with patients' overall assessment of improvement. These domains and their respective outcome measures can be used to improve assessment of patients' response to treatment.

Topics: Analgesics; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Placebos; Pregabalin; Randomized Controlled Trials as Topic; Sleep; Surveys and Questionnaires; Treatment Outcome

Topics: Analgesics; Bone Plates; Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Neuroma; Neurosurgical Procedures; Pain; Paresthesia; Peripheral Nerve Injuries; Peripheral Nervous System Neoplasms; Pregabalin; Radial Nerve; Radius Fractures; Ultrasonography

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Stroke

Numerous controlled clinical trials have demonstrated the safety and efficacy of pregabalin in the treatment of neuropathic pain. The objectives of the present study were to assess the impact of pregabalin under real-world conditions on pain, pain-related sleep interference and general well-being, and to assess the tolerability and safety of pregabalin in patients diagnosed with neuropathic pain of central or peripheral origin.. This was a non-interventional, multicentre study in which pregabalin was administered for 8 weeks, at the therapeutic dosages of 150-600 mg/day, to patients with a diagnosis of neuropathic pain. Pain intensity and pain-related sleep interference were measured using 11-point numerical rating scales, while well-being was assessed by documenting how often emotions associated with anxiety or depression were felt over the past week. Patient and Clinician Global Impression of Change (PGIC and CGIC) were assessed at the final visit.. In the 668 patients included in the full analysis set, there were significant (p < 0.0001) reductions in mean pain and pain-related sleep interference scores of 4.16 and 4.02, respectively. Indicators of general well-being showed improvement from baseline to final visit. The majority of patients were rated as 'much improved' (43.7% and 36.7%) or 'very much improved' (24.0% and 26.2%) on CGIC and PGIC scores, respectively. Discontinuation because of lack of efficacy occurred in 0.7% of 691 patients in the safety analysis set while discontinuation because of adverse events occurred in 5.1% of this population; 76.4% continued treatment after the study ended.. Significant reductions in pain and pain-related sleep interference, combined with reductions in feelings of anxiety and depression, suggest that pregabalin under real-world conditions improves the overall health and well-being of patients with neuropathic pain.

Topics: Aged; Analgesics; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Peripheral Nervous System Diseases; Pregabalin; Product Surveillance, Postmarketing; Sleep Wake Disorders; Surveys and Questionnaires

Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia.. Male Sprague-Dawley rats (180-200 g) were implanted with osmotic mini-pumps filled with morphine (90 μg · μl⁻¹ · h⁻¹) or saline (0.9% w/v). On days 7-10 in isoflurane anesthetized animals, we evaluated the effects of (1) systemic pregabalin on spinal neuronal and visceromotor responses, and (2) spinal ondansetron on dorsal horn neuronal response. Messenger ribonucleic acid concentrations of α2δ-1, 5HT3A, and μ-opioid receptor in the dorsal root ganglia of all animals were analyzed.. In morphine-treated animals, evoked spinal neuronal responses were enhanced to a subset of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%); the visceromotor response to a subset of colorectal distension pressures was attenuated by pregabalin (52.8%; n = 8 for all measures, P < 0.05). Messenger ribonucleic acid concentrations were unchanged.. The inhibitory action of pregabalin in opioid-induced hyperalgesia animals is neither neuropathy-dependent nor reliant on up-regulation of the α₂δ-1 subunit of voltage-gated calcium channels-mechanisms proposed as being essential for pregabalin's efficacy in neuropathy. In opioid-induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be up-regulated, creating an environment that is permissive for pregabalin-mediated analgesia without peripheral pathology.

Topics: Analgesics; Analgesics, Opioid; Animals; Dilatation; Electrophysiology; gamma-Aminobutyric Acid; Hyperalgesia; Male; Morphine; Neurons; Ondansetron; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Receptors, Serotonin, 5-HT3; Rectum; RNA, Messenger; Serotonin Antagonists; Spinal Cord

Milnacipran and duloxetine, serotonin/noradrenalin reuptake inhibitors, and pregabalin, a alpha(2)-delta(1) Ca(2+) channel blocker, are efficacious against fibromyalgia, a condition characterized by diffuse chronic pain and associated with stress. We compared these compounds (i.p. route), in rat models of acute/inflammatory pain (2.5% intraplantar formalin) and stress-induced ultrasonic vocalization (USV: 22kHz calls following presentation of a conditioned stimulus previously associated with foot-shocks). In the formalin test, milnacipran dose-dependently attenuated paw elevation and licking (minimal effective dose, MED: 2.5mg/kg for licking/late phase). Duloxetine was slightly more potent (MED=0.63). Pregabalin also reduced paw licking/late phase (MED=0.63), but was inactive up to 160mg/kg for paw elevation (both phases) and paw licking (early phase). Milnacipran dose-dependently reduced USV (MED=10, near total inhibition at 20mg/kg); duloxetine was less potent (MED=20). Pregabalin (2.5-80mg/kg) was only significantly active at 40mg/kg. Milnacipran, duloxetine and pregabalin possess analgesic activity in the formalin test on paw licking/late phase (corresponding to inflammatory pain with a central sensitization component). In the stress-induced USV model, milnacipran was the most potent and efficacious compound. To summarize, reduction of formalin-induced paw licking/late phase might constitute a useful indicator of potential activity against inflammatory/centrally sensitized pain, as might be expressed in fibromyalgia.

Topics: Adrenergic Uptake Inhibitors; Analgesics; Analysis of Variance; Animals; Cyclopropanes; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Electroshock; Formaldehyde; gamma-Aminobutyric Acid; Male; Milnacipran; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley; Stress, Physiological; Thiophenes; Vocalization, Animal

Fibromyalgia is a chronic pain disorder characterized by widespread pain, stiffness, insomnia, fatigue and distress. Several randomized controlled trials (RCTs) have shown moderate effectiveness of pharmacological therapies for fibromyalgia pain. Evidence from these trials suggests that pharmacological therapy can not only improve pain but also fatigue, function and well-being in patients with fibromyalgia. Duloxetine and milnacipran, two highly selective serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the alpha(2)delta agonist pregabalin have been approved by the US FDA for the treatment of fibromyalgia symptoms. In general, about half of all treated patients seem to experience a 30% reduction of symptoms, suggesting that many patients with fibromyalgia will require additional therapies. Thus, other forms of treatment, including exercise, cognitive behavioural therapies and self-management strategies, may be necessary to achieve satisfactory treatment outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor agonists and sodium channel antagonists have so far been disappointing for patients with fibromyalgia. However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising.

Topics: Age Factors; Analgesics, Opioid; Calcium Channel Blockers; Clinical Trials as Topic; Cognitive Behavioral Therapy; Combined Modality Therapy; Dopamine Agonists; Duloxetine Hydrochloride; Exercise; Exercise Therapy; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Pain Threshold; Pregabalin; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Research Design; Self Care; Thiophenes; Treatment Outcome

To determine the utility of substitution of pregabalin (PGB) for gabapentin (GBP) therapy in the relief of neuropathic pain (NeP) in patients with peripheral neuropathy (PN).. A cohort study was performed examining PGB substitution in patients who were GBP responders (> or =30% NeP relief on a visual analog scale [VAS]) or GBP nonresponders after prolonged GBP use, with further comparison to patients receiving continuous GBP therapy.. Patients with PN and related NeP requiring GBP therapy were evaluated in a tertiary care neurological clinic at 0, 6, and 12 months.. Pain severity (Visual Analog Score [VAS]) was the primary outcome measure, while quality of life (European Quality of Life - 5 Domains [EQ-5D] and EQ-5D VAS) and occurrence of adverse events were secondary outcome measures.. Both GBP responder and nonresponder groups had additional NeP relief of about 25% following substitution of PGB after 6 and 12 months, while improved EQ-5D VAS was identified in the GBP nonresponder group. There were no serious adverse events for either medication, while GBP nonresponders discontinued PGB in more than 30% of cases due to inefficacy or adverse events.. Randomized, controlled, blinded head-to-head studies of GBP and PGB have not been published. The results of this open-label assessment of PGB substitution for GBP suggest that PGB may provide additional pain relief and possible improvement in quality of life above that received by GBP use in patients with NeP due to PN.

Topics: Aged; Amines; Analgesics; Cohort Studies; Cyclohexanecarboxylic Acids; Data Interpretation, Statistical; Female; Follow-Up Studies; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Peripheral Nervous System Diseases; Pregabalin; Quality of Life; Treatment Outcome

Topics: Administration, Topical; Analgesics; Capsaicin; Diabetic Neuropathies; Drug Combinations; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Ointments; Pain; Pain Measurement; Peripheral Nervous System Diseases; Pregabalin

Topics: Analgesics; Clinical Trials as Topic; Data Interpretation, Statistical; Diabetic Neuropathies; Endpoint Determination; gamma-Aminobutyric Acid; Humans; Outcome Assessment, Health Care; Pain; Pain Measurement; Pregabalin; Quality of Life; Reproducibility of Results; Self-Assessment

Topics: Administration, Topical; Analgesics, Non-Narcotic; Animals; Behavior, Animal; gamma-Aminobutyric Acid; Neural Pathways; Pain; Pain Management; Peripheral Nervous System Diseases; Pregabalin; Rats

Pregabalin exhibits potent anticonvulsant, analgesic, and anxiolytic activity in animal models. However, few studies have evaluated pregabalin's potential peripheral effects on neuropathic pain. The aim of this study was to evaluate the peripheral analgesic effects of pregabalin in a rat model of neuropathic pain.. Male Sprague-Dawley rats were prepared by ligating the left L5 and L6 spinal nerves to produce neuropathic pain. Sixty rats with neuropathic pain were randomly assigned to six groups. Normal saline (control) and pregabalin (10, 20, 30, and 50 mg.kg(-1)) were administered to the plantar surface of the affected left hind paw. Pregabalin (50 mg.kg(-1)) was administered into the unaffected contralateral paw in order to determine its systemic effect. Responses to mechanical, cold, and heat stimulation were recorded at 15, 30, 60, 90, 120, 150, and 180 min after drug administration. Rotarod performance was measured to detect drug-induced side effects, including sedation and reduced motor coordination.. Saline injected into the affected paw and a pregabalin dose of 50 mg.kg(-1) injected into the contralateral paw showed no differences for mechanical, cold, and heat allodynia. Administration of pregabalin to the affected left hind paw in the dose range of 10-50 mg.kg(-1) resulted in a dose-dependent increase in thresholds to mechanical, cold, and heat stimulation.. Peripherally administered pregabalin attenuates mechanical, cold, and heat allodynia in a rat model of neuropathic pain.

Topics: Analgesics, Non-Narcotic; Animals; Behavior, Animal; Cold Temperature; Dose-Response Relationship, Drug; Foot; gamma-Aminobutyric Acid; Hot Temperature; Injections; Male; Pain; Pain Measurement; Pain Threshold; Peripheral Nervous System Diseases; Physical Stimulation; Postural Balance; Pregabalin; Rats; Rats, Sprague-Dawley; Spinal Nerves

The objective of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) model of the static allodynia response to pregabalin with and without sildenafil in a chronic constriction injury model of neuropathic pain. Six treatment groups were evaluated every 30 min for 6 h. Rats were treated with either 1) a saline infusion; 2) a 2-h pregabalin infusion at 4 mgxkg(-1)xh(-1); 3) a 2-h pregabalin infusion at 10 mgxkg(-1)xh(-1); 4) a 2.2-mg loading dose + 12 mgxkg(-1)xmin(-1) infusion of sildenafil; 5) a 2-h pregabalin infusion at 1.6 mgxkg(-1)xh(-1) with sildenafil; and 6) a 2-h infusion of pregabalin at 4 mgxkg(-1)xh with sildenafil. The static allodynia endpoint was modeled by using three population PD approaches: 1) the behavior of the injured paw using a three-category ordinal logistic regression model; 2) paw withdrawal threshold (PWT) (g) between the injured and uninjured paw using the Hill equation with a baseline function; and 3) the baseline normalized difference in PWT between the injured and uninjured paw. The categorical model showed a significant shift in the concentration-response relationship of pregabalin to lower concentrations with concomitant sildenafil. Likewise, the continuous PK-PD models demonstrated a reduction in the EC(50) of pregabalin necessary for PD response in the presence of sildenafil. The difference-transformed PD model resulted in a 54.4% (42.3-66.9%) decrease in EC(50), whereas the percentage-transformed PD model demonstrated a 53.5% (42.7-64.3%) shift. It is concluded from these studies that there is a synergistic PD interaction between pregabalin and sildenafil.

Topics: Analgesics; Animals; Calcium Channels; Chronic Disease; Drug Interactions; gamma-Aminobutyric Acid; Hyperalgesia; Ion Channel Gating; Ligands; Male; Models, Biological; Pain; Pain Threshold; Phosphodiesterase 5 Inhibitors; Piperazines; Pregabalin; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones

The superficial radial vein at the lateral edge of the inferior third of the forearm and of the wrist has strong anatomical relationship with the sensory superficial branch of the radial nerve. At this level, any venous puncture may be responsible for a lesion of this superficial part of the radial nerve. We report two cases of dysesthesia in the radial territory after this kind of puncture. This risk should not be neglected and venous puncture should be avoided in this area.

Topics: Analgesics, Non-Narcotic; Colonoscopy; Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Nerve Block; Pain; Pregabalin; Radial Nerve; Regional Blood Flow; Vaginal Neoplasms; Veins

Pregabalin, primarily used to manage neuropathic pain and fibromyalgia, is categorized as a Schedule V drug (ie, lowest potential for abuse) in the US Drug Enforcement Administration's Controlled Substances Act. Because pregabalin is not recognized as a drug with high-abuse potential, data on pregabalin abuse and addiction are lacking. The authors report a case of a 35-year-old woman with a history of opioid-seeking behavior who was prescribed pregabalin for pain control. The patient requested an increase in her medication 2 months after beginning treatment and, after her physician denied her request, subsequently obtained pregabalin from other sources. Over a 28-day period, the patient received a total of 88,500 mg of pregabalin. After learning of the other prescriptions, the patient's physician became suspicious of pregabalin abuse or diversion. In accordance with state medical board guidelines, the patient was discharged from the practice and referred to a local detoxification center.

Topics: Adult; Analgesics; Analgesics, Opioid; Behavior, Addictive; Female; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Risk Factors; Substance-Related Disorders

To evaluate changes in healthcare resource use and costs after initiating pregabalin or duloxetine in employees with pain associated with diabetic peripheral neuropathy (pDPN).. Employees (18-64 years old) with a DPN diagnosis and at least one pDPN-related pain medication claim were identified using the MarketScan Commercial Database (2005-2008). Propensity scored matched pregabalin and duloxetine new starts were evaluated in the 6-month pre- and 6-month post-initiation periods. Study outcomes including imputed medically-related work loss, prescription and healthcare utilization, and associated expenditures were analyzed using univariate statistics and multivariate models in a difference-in-difference approach.. A total of 473 employees in each treatment group were identified. Mean age was 53.6 (SD 7.0) years for pregabalin and 53.5 (SD 7.4) years for duloxetine. There were no pre-index differences between groups. Adjusted marginal effects were not statistically significant for pre-to-post changes in opioid utilization (p = 0.328), number of pDPN-related analgesic medications (p = 0.506), all-cause healthcare costs (p = 0.895), indirect costs (p = 0.324), or pDPN-attributable expenditures (p = 0.359).. Claims analysis is limited in accounting for all patient and plan differences, and by the reliability of medical claims for diagnosis coding. The sample size of the matched cohorts may have limited the power of the analysis to detect differences.. There were no significant pre-to-post differences between pregabalin and duloxetine treatment groups in pDPN-related analgesic medication use, or pDPN-attributable, all-cause, and indirect expenditures.

Topics: Adolescent; Adult; Age Factors; Analgesics; Comorbidity; Diabetic Neuropathies; Duloxetine Hydrochloride; Female; gamma-Aminobutyric Acid; Health Services; Humans; Insurance Claim Review; Male; Middle Aged; Pain; Pregabalin; Sex Factors; Socioeconomic Factors; Thiophenes; Young Adult

Topics: Anticonvulsants; Botulinum Toxins, Type A; Epilepsia Partialis Continua; Fructose; gamma-Aminobutyric Acid; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pain; Pregabalin; Radionuclide Imaging; Supratentorial Neoplasms; Topiramate

Topics: Adolescent; Analgesics; Anemia, Sickle Cell; Chin; gamma-Aminobutyric Acid; Humans; Male; Pain; Pregabalin; Somatosensory Disorders; Treatment Outcome

A major symptom of persistent neuropathic pain, which may develop after peripheral nerve injury, is hypersensitivity (allodynia) to normally innocuous cold stimuli. Although the anticonvulsant pregabalin has been demonstrated to relieve neuropathic pain, both in preclinical models and clinically, the analgesic effect of the drug in animals has not been profiled for cold hypersensitivity. Therefore, we examined the effect of pregabalin (single oral dosing: 30, 100, 300 micromol/kg) on cold allodynia in two models of chronic neuropathic pain, the spared nerve injury (SNI) and the spinal nerve ligation (SNL) models. A significant antiallodynic effect was observed with pregabalin at all doses tested with a maximal effect of 71% (SNI) and 60% (SNL), respectively compared to vehicle. For comparison, only the highest dose tested of pregabalin (300 micromol/kg), significantly decreased pain responses in phase 2 of the rat formalin test (approximately 67% pain inhibition). However, pregabalin at this high dose also affected other centrally mediated behavioural functions, such as motor activity and anxiolytic behaviour in naïve animals, which could potentially interfere with the pain readout. The present study demonstrates that oral administration of pregabalin significantly reduces both cold allodynia induced in the SNI and the SNL models of neuropathic pain as well as formalin-induced nociception, albeit with different sensitivity and potency.

Topics: Administration, Oral; Analgesics; Animals; Behavior, Animal; Chronic Disease; Cold Temperature; Disease Models, Animal; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Male; Motor Activity; Pain; Pain Measurement; Peripheral Nervous System Diseases; Pregabalin; Rats; Rats, Sprague-Dawley

Cyclooxygenase (COX) contributes to neuropathic pain after peripheral nerve injury, yet COX inhibitors are generally ineffective against mechanical allodynia and hyperalgesia in neuropathic pain patients and animal models. In the present study, we investigated the effects of etodolac, a selective COX-2 inhibitor, on mechanical allodynia in mice after partial sciatic nerve ligation (PSNL) compared to indomethacin (a nonselective COX inhibitor) or celecoxib (a selective COX-2 inhibitor). PSNL decreased the paw-withdrawal threshold (PWT) as assessed by the von Frey hair test, and etodolac, but not indomethacin or celecoxib, administered daily for two weeks, partially or wholly reversed the decrease. The efficacy of etodolac gradually increased throughout the administration period, and the higher dosages restored preligation PWT values by day 21. The positive control pregabalin also partially or wholly reversed the decrease in PWT, but in contrast to etodolac, it showed no increase in efficacy throughout the administration period. In normal mice, etodolac did not affect the PWT, whereas pregabalin increased it. These findings suggest that the mechanisms of inhibition of mechanical allodynia by etodolac and pregabalin are different and demonstrate that in contrast to other COX inhibitors, etodolac is effective against mechanical allodynia in a mouse neuropathic pain model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Celecoxib; Cyclooxygenase 2 Inhibitors; Edema; Etodolac; gamma-Aminobutyric Acid; Indicators and Reagents; Ligation; Male; Mice; Pain; Pain Measurement; Pregabalin; Pyrazoles; Sciatic Neuropathy; Sulfonamides

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is estimated to affect 4-8 million US adults. The exact molecular mechanisms underlying this illness remain unclear, rendering most clinical treatment and management techniques relatively ineffective. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient) to condition the onset and maintenance of FMS. These same systemic abnormalities are thought to be responsible for the loss of cephalic gray matter density observed in all FMS patients groups studied to date. The current scope of FMS treatment focuses largely on analgesia and does not clearly address potential neuroprotective strategies. This article proposes a combined treatment of pregabalin and memantine to decrease the pain and rate of gray matter atrophy associated with FMS. This dual-drug therapy targets the voltage-gated calcium ion channel (VGCC) and the N-methyl d-aspartate receptor (NMDAR) (respectively), two primary components of the human nociceptive and pain processing systems.

Topics: Analgesics; Chronic Disease; Drug Therapy, Combination; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Memantine; Neuroprotective Agents; Pain; Pregabalin

The Fibromyalgia Impact Questionnaire (FIQ) is a disease-specific composite instrument that measures the effect of problems experienced by patients with fibromyalgia (FM). Utilization of the FIQ in measuring changes due to interventions in FM requires derivation of a clinically meaningful change for that instrument. Analyses were conducted to estimate the minimal clinically important difference (MCID), and to propose FIQ severity categories.. Data from 3 similarly designed, 3-month placebo-controlled, clinical treatment trials of pregabalin 300, 450, and 600 mg/day in patients with FM were modeled to estimate the change in the mean FIQ total and stiffness items corresponding to each category on the Patient Global Impression of Change. FIQ severity categories were modeled and determined using established pain severity cutpoints as an anchor.. A total of 2228 patients, mean age 49 years, 93% women, with a mean baseline FIQ total score of 62 were treated in the 3 studies. Estimated MCID on a given measure were similar across the studies. In a pooled analysis the estimated MCID (95% confidence interval) was 14% (13; 15) and for FIQ stiffness it was 13% (12; 14). In the severity analysis a FIQ total score from 0 to <39 was found to represent a mild effect, >or= 39 to <59 a moderate effect, and >or=59 to 100 a severe effect.. The analysis indicates that a 14% change in the FIQ total score is clinically relevant, and results of these analyses should enhance the clinical utility of the FIQ in research and practice.

Topics: Analgesics; Disability Evaluation; Female; Fibromyalgia; gamma-Aminobutyric Acid; Health Status; Humans; Male; Middle Aged; Pain; Pregabalin; Randomized Controlled Trials as Topic; Severity of Illness Index; Sickness Impact Profile; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Analgesics, Non-Narcotic; Duloxetine Hydrochloride; Female; gamma-Aminobutyric Acid; Humans; Leiomyoma; Pain; Pregabalin; Selective Serotonin Reuptake Inhibitors; Skin Neoplasms; Thiophenes

Effects of pregabalin (PGB, 20-80 mg/kg i.v. injection) on spinally-organized nociception were investigated in isoflurane-anesthetized intact and spinalized rats. Responses of single deep spinal dorsal horn (DH) (laminae IV-V) nociceptive-specific (NS) neurons receiving peripheral inputs from A-delta and C fibers to repetitive electrical stimulation (intensity: 3-5 mA; frequency: 1 Hz; pulse duration: 1 ms), mechanical/heat stimulation were recorded extracellularly during physiological condition and s.c. bee venom (BV) induced inflammation. PGB significantly inhibited C-fiber mediated spinal NS neurons' late responses including phenomena of wind-up (temporal summation) and after-discharge. However, the antinociceptive effects of PGB on nociception were not observed until 30 min after its administration. In contrast, no significant inhibitory effect of PGB on A-delta fiber mediated early responses was observed during the experiments. Compared with intact rats, the inhibitory effects of PGB upon nociception vanished in the spinalized animals. This suggests that PGB-induced selective antinociceptive effect on C-fiber mediated nociception is mainly central effects involving supraspinal centers via descending inhibitory controls. Furthermore, pre-treatment, but not post-treatment, with PGB (80 mg/kg) markedly inhibited s.c. BV elicited spontaneous neuronal responses, and noxious mechanical/heat stimuli evoked hyperactivities of spinal NS neurons, indicating that PGB has efficacy of pre-emptive analgesia on pathological pain associated with central sensitization.

Topics: Animals; Anticonvulsants; Decerebrate State; Electric Stimulation; gamma-Aminobutyric Acid; Male; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Neurons; Pain; Pregabalin; Rats; Rats, Wistar; Spinal Cord

Topics: Amines; Analgesics; Anticonvulsants; Cyclohexanecarboxylic Acids; Fibromyalgia; Gabapentin; gamma-Aminobutyric Acid; Humans; Nervous System Diseases; Pain; Pregabalin; Rheumatic Diseases; Rheumatology

Topics: Analgesics; Anxiety; Depression; Dose-Response Relationship, Drug; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Pregabalin; Women's Health

Cold allodynia is a frequent clinical symptom of patients with neuropathic pain. Despite numerous studies of cold allodynia, using animal models of neuropathic pain, little is known about its underlying mechanisms. This study was performed to establish a method for the pharmacologic evaluation of cold allodynia using several analgesics in a chronic constriction injury (CCI) rat model of neuropathic pain. Compared with the results obtained before the CCI operation, the CCI rats placed on a cork plate at 20 degrees C exhibited a slight change in the paw withdrawal latency because of the mechanical stimulus mediated by the injured paw touching the plate. By contrast, there was a significant reduction in the paw withdrawal latency on a cold metal plate compared with that on the cork plate after the CCI surgery, with the maximum decrease occurring on postoperative day 7. This reduction is thought to specifically reflect cold-induced pain behavior. In addition, both naïve and CCI rats showed behavioral changes at 5 and 0 degrees C, but not at 10 degrees C or higher. Interestingly, a subcutaneous morphine dose of 6 mg/kg completely inhibited cold allodynia induced at 10 degrees C on postoperative day 7. Under this condition, both the sodium channel blocker mexiletine (10 and 30 mg/kg, subcutaneously) and the calcium channel alpha2delta subunit blocker pregabalin (30 and 100 mg/kg, orally) significantly suppressed cold allodynia. Additionally, both resiniferatoxin (0.3 mg/kg, subcutaneously), an ultrapotent analog of capsaicin that desensitizes C fibers, and the VR1 channel antagonist N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide (10 and 30 mg/kg, orally) significantly prolonged the paw withdrawal latency. In conclusion, our data suggest that the activation of C fibers mediates cold allodynia.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Calcium Channel Blockers; Chronic Disease; Cold Temperature; Constriction, Pathologic; Disease Models, Animal; Diterpenes; gamma-Aminobutyric Acid; Male; Mexiletine; Morphine; Nerve Fibers, Unmyelinated; Pain; Pain Measurement; Peripheral Nervous System Diseases; Pregabalin; Pyrazines; Pyridines; Rats; Rats, Sprague-Dawley; Reaction Time; Sciatic Nerve; Sodium Channel Blockers; TRPV Cation Channels

Chronic post-ischemia pain was induced in anesthetized rats by placing a tourniquet at the ankle joint for 3 h, and removing it to allow reperfusion. The effectiveness of standard analgesic drugs to attenuate mechanical allodynia was assessed 2 and 7 days after ischemia/reperfusion. Only high doses of morphine, dexamethasone and pregabalin partially reduced mechanical allodynia 2 days post-ischemia/reperfusion, while other treatments (ibuprofen, acetaminophen, amitriptyline) were not effective. Furthermore, only the highest dose of pregabalin reduced mechanical allodynia 7 days post-ischemia/reperfusion. These results are consistent with findings that complex region pain syndrome-I pain is refractory to most standard analgesic treatments.

Topics: Amitriptyline; Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Hindlimb; Ischemia; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Physical Stimulation; Pregabalin; Rats; Rats, Long-Evans; Reflex Sympathetic Dystrophy; Regional Blood Flow; Reperfusion Injury

Pregabalin is used for treatment of neuropathic pain conditions. The present study evaluated effects of pregabalin in 2 rat models of muscle-induced hyperalgesia: Inflammatory and noninflammatory. Muscle hyperalgesia (withdrawal threshold to compression of the muscle) and cutaneous hyperalgesia of the paw (withdrawal threshold to von Frey filaments) were measured before and after induction of hyperalgesia and after treatment with pregabalin (saline, 10 to 100 mg/kg i.p.). In the inflammatory model, 3% carrageenan injected into 1 gastrocnemius muscle decreased the mechanical withdrawal threshold of the paw bilaterally and the compression withdrawal threshold of the muscle ipsilaterally 2 weeks later. Pregabalin (10 to 100 mg/kg) increased the compression withdrawal threshold of the inflamed muscle when compared with vehicle controls. Pregabalin also increased the mechanical withdrawal threshold of the paw bilaterally, but only with 100 mg/kg. In the noninflammatory model, 2 unilateral injections of acidic saline into the gastrocnemius muscle produced bilateral cutaneous and muscle hyperalgesia 24 hours after the second injection. Pregabalin (10 to 100 mg/kg i.p.) significantly increased the compression withdrawal thresholds of the muscle and the mechanical withdrawal threshold of the paw bilaterally when compared with vehicle. However, pregabalin also has significant motor effects at the higher doses (60 to 100 mg/kg). Therefore, pregabalin reduces both muscle and cutaneous hyperalgesia that occurs after muscle insult in 2 animal models of muscle pain at doses that do not produce ataxia.. This study shows that pregabalin reduces both cutaneous and muscle hyperalgesia in inflammatory and noninflammatory models of muscle pain. Thus, pregabalin may be an effective treatment for people with chronic muscle pain.

Topics: Analgesics; Animals; Carrageenan; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Functional Laterality; gamma-Aminobutyric Acid; Hyperalgesia; Male; Motor Activity; Muscle, Skeletal; Muscular Diseases; Pain; Pain Threshold; Pregabalin; Rats; Rats, Sprague-Dawley; Reaction Time; Skin; Time Factors

Chronic muscle pain is a problem with high prevalence in clinical practice and its pharmacological treatment is difficult. There is a lack of animal models which reliably predict analgesic activity of drugs on muscle pain. Here we used intramuscular injection of tumor necrosis factor-alpha (TNF) in rats as a model of muscle pain. In this model we tested the antihyperalgesic action of lacosamide in comparison to the analgesics pregabalin and gabapentin. Mechanical withdrawal thresholds to muscle pressure were measured with an algesimeter exerting pressure on the gastrocnemius muscles previously injected with TNF. Fore limb grip strength was measured with a digital grip force meter after TNF injection into the biceps brachii muscles. A complete reversal of hyperalgesia was seen with lacosamide at 30mg/kg. Significant effects were also seen for pregabalin at 30 and 100mg/kg and gabapentin at 100mg/kg. In biceps muscle hyperalgesia, a significant reversal of hyperalgesia was seen with lacosamide at 10mg/kg. Significant effects were also seen for pregabalin and gabapentin at 100mg/kg. We could thus demonstrate in a rat model for myalgia that lacosamide effectively reduces muscular hyperalgesia and is somewhat more potent than gabapentin and pregabalin.

Topics: Acetamides; Amines; Animals; Behavior, Animal; Cyclohexanecarboxylic Acids; Excitatory Amino Acid Antagonists; Gabapentin; gamma-Aminobutyric Acid; Hand Strength; Hyperalgesia; Lacosamide; Male; Muscular Diseases; Pain; Pregabalin; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factors

Clinical studies investigating the use of pregabalin and duloxetine for the management of diabetic peripheral neuropathy and post-herpetic neuralgia are reviewed. The benefits and potential drawbacks associated with these agents are discussed.

Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain; Pregabalin; Randomized Controlled Trials as Topic; Thiophenes

Topics: Adverse Drug Reaction Reporting Systems; Analgesics; Anti-Anxiety Agents; Body Weight; Conflict of Interest; Controlled Clinical Trials as Topic; GABA Agonists; gamma-Aminobutyric Acid; Humans; Pain; Placebo Effect; Pregabalin; Reproducibility of Results; Research Design; Spinal Cord Injuries; Substance Withdrawal Syndrome; Synaptic Transmission; Treatment Outcome

A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition.

Topics: Amitriptyline; Analgesics; Anti-Ulcer Agents; Anticoagulants; Antidepressive Agents; Anxiety; Cardiotonic Agents; Cataract; Cataract Extraction; Cholecystectomy; Chronic Disease; Citalopram; Digoxin; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Hypertension; Hysterectomy; Lorazepam; Middle Aged; Mitral Valve Insufficiency; Omeprazole; Ovarian Neoplasms; Pain; Pregabalin; Sterilization, Tubal; Stomach Diseases; Vulvar Diseases

Topics: Adult; Analgesics; Antidepressive Agents; Dose-Response Relationship, Drug; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Somatoform Disorders; Treatment Outcome

Topics: Administration, Oral; Analgesics; Drug Administration Schedule; Drug Costs; Drug Interactions; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pain Measurement; Pregabalin; Treatment Outcome

Pregabalin is often used for the treatment of chronic pain syndromes. We here describe two patients with chronic pain and pregabalin-induced myoclonic status epilepticus. Patients treated with pregabalin who experience sudden behavioral changes or mycloni should be investigated for this possible side effect, and pregabalin should be reduced or discontinued if myocloni or status epilepticus occurs.

Topics: Aged, 80 and over; Analgesics; Chronic Disease; Electroencephalography; Epilepsies, Myoclonic; Female; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain; Pregabalin

We report two patients with refractory epilepsy who developed unilateral painful gynecomastia and lower extremity pain (one of them localized and the other one diffuse), shortly after receiving Pregabalin (PGB). Neither of them had previous endocrinologic problems or complaints about pain on their medical history. PGB was stopped in one patient and reduced in the other one, with complete disparition of the symptoms in the following weeks in both patients. This supports the hypothesis that gynecomastia could be a drug-induced and easy to manage secondary effect of PGB, with a higher incidence than observed on previous clinical trials.

Topics: Adolescent; Anticonvulsants; Edema; Epilepsy; gamma-Aminobutyric Acid; Gynecomastia; Humans; Ilium; Lower Extremity; Magnetic Resonance Imaging; Male; Pain; Pregabalin

Neuropathic pain is a debilitating condition affecting millions of people around the world and is defined as pain that follows a lesion or dysfunction of the nervous system. This type of pain is difficult to treat, but the novel compounds pregabalin (Lyrica) and gabapentin (Neurontin) have proven clinical efficacy. Unlike traditional analgesics such as nonsteroidal antiinflammatory drugs or narcotics, these agents have no frank antiinflammatory actions and no effect on physiological pain. Although extensive preclinical studies have led to a number of suggestions, until recently their mechanism of action has not been clearly defined. Here, we describe studies on the analgesic effects of pregabalin in a mutant mouse containing a single-point mutation within the gene encoding a specific auxiliary subunit protein (alpha2-delta-1) of voltage-dependent calcium channels. The mice demonstrate normal pain phenotypes and typical responses to other analgesic drugs. We show that the mutation leads to a significant reduction in the binding affinity of pregabalin in the brain and spinal cord and the loss of its analgesic efficacy. These studies show conclusively that the analgesic actions of pregabalin are mediated through the alpha2-delta-1 subunit of voltage-gated calcium channels and establish this subunit as a therapeutic target for pain control.

Topics: Amino Acid Sequence; Analgesics; Animals; Arginine; Autoradiography; Base Sequence; Calcium Channels; Calcium Channels, N-Type; Cell Line; Chlorocebus aethiops; Constriction, Pathologic; Female; Formaldehyde; gamma-Aminobutyric Acid; Ion Channel Gating; Male; Mice; Mice, Transgenic; Mutation; Pain; Pregabalin; Protein Binding; Protein Subunits; Swine

Topics: Anticonvulsants; Denmark; Drug and Narcotic Control; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain; Pregabalin

Topics: Calcium Channel Blockers; Calcium Channels, N-Type; Chronic Disease; gamma-Aminobutyric Acid; Humans; NAV1.8 Voltage-Gated Sodium Channel; Neurons, Afferent; omega-Conotoxins; Pain; Peptides; Pregabalin; Sodium Channels

Topics: Anticonvulsants; Diabetic Neuropathies; Documentation; Drug Information Services; gamma-Aminobutyric Acid; Humans; Pain; Practice Guidelines as Topic; Pregabalin

Topics: Analgesics; Anticonvulsants; Drugs, Investigational; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

Topics: Anticonvulsants; Chronic Disease; Controlled Clinical Trials as Topic; Drug Interactions; Epilepsy; Evidence-Based Medicine; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin

A series of mutual prodrugs derived from gabapentin, pregabalin, memantine, venlafaxine were synthesized and their pharmacological properties to treat neuropathic pain were investigated in a rat model of chronic sciatic nerve constriction injury (CCI). In vivo evaluation demonstrated that the mutual prodrugs 2002413A, 2002823A composed of two gabapentins, 2002414 composed of gabapentin and pregabalin were effective in reversal tactile allodynia in CCI rats. The prodrugs 2002413A, 2002414 had no significant influence on the rotarod activity. The result suggest that the prodrugs may be possible candidates for further development.

Topics: Amines; Animals; Chronic Disease; Cyclohexanecarboxylic Acids; Cyclohexanols; Disease Models, Animal; Gabapentin; gamma-Aminobutyric Acid; Memantine; Pain; Pain Threshold; Pregabalin; Prodrugs; Rats; Sciatic Neuropathy; Structure-Activity Relationship; Venlafaxine Hydrochloride

Topics: Animals; Antiparkinson Agents; Carbazoles; gamma-Aminobutyric Acid; Humans; Indoles; Neuroprotective Agents; Pain; Peripheral Nervous System Diseases; Pregabalin; Prodrugs; Stroke

Anticonvulsants that act as ligands at alpha(2)delta subunits of voltage-gated calcium channels are proving to be novel treatments for chronic pain.

Topics: Acetates; Amines; Anticonvulsants; Calcium Channels; Chronic Disease; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Ligands; Pain; Pain Measurement; Pregabalin; Somatoform Disorders; Synaptic Transmission

The antiepileptic drug, gabapentin, and another structurally related compound, pregabalin, are increasingly employed in the pharmacotherapy of chronic pain states, although their primary mechanism of action remains a topic of active study. A genomic approach to the study of these drugs may elucidate their potentially novel mechanisms. We examined the heritability of sensitivity to analgesia from gabapentin and pregabalin as a precursor to linkage mapping efforts. Accordingly, 11 inbred mouse strains were tested for inhibition of nociception by gabapentin or pregabalin (50-300 mg/kg, i.p.) in two different preclinical assays of inflammatory pain, the formalin test (5% formalin; 20 microl) and zymosan thermal hyperalgesia on the paw-withdrawal test (3 mg/ml zymosan; 20 microl). Significant strain-dependence of drug action was noted in each case, indicating that sensitivity to these analgesics is heritable. Furthermore, the pattern of strain sensitivities to gabapentin and pregabalin were mostly similar, supporting the notion that they act via similar genetic and physiological mechanisms. However, there was virtually no correlation between strain sensitivities to pregabalin inhibition of formalin nociception and zymosan thermal hyperalgesia. In light of previous data from our laboratory and others regarding morphine analgesia, we now establish and empirically demonstrate the general principle that pharmacogenetic mechanisms underlying analgesic sensitivity are specific to the type of pain being inhibited. This has considerable implications for ongoing pharmacogenetic investigations and, more generally, for the choices of preclinical models of pain used in drug development.

Topics: Acetates; Amines; Analgesia; Animals; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Female; Gabapentin; gamma-Aminobutyric Acid; Genotype; Male; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Pain; Pain Measurement; Pharmacogenetics; Pregabalin; Species Specificity

Topics: Acetaminophen; Acetates; Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Delivery Systems; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nitrates; Pain; Peripheral Nervous System Diseases; Piracetam; Pregabalin; Topiramate

Spinal cord stimulation (SCS) is an effective tool in alleviating neuropathic pain. However, a number of well-selected patients fail to obtain satisfactory pain relief. Previous studies have demonstrated that i.t. baclofen and/or adenosine can enhance the SCS effect, but this combined therapy has been shown to be useful in less than half of the cases and more effective substances are therefore needed. The aim of this experimental study in rats was to examine whether gabapentin or pregabalin attenuates tactile allodynia following partial sciatic nerve injury and whether subeffective doses of these drugs can potentiate the effects of SCS in rats which do not respond to SCS. Mononeuropathy was produced by a photochemically induced ischaemic lesion of the sciatic nerve. Tactile withdrawal thresholds were assessed with von Frey filaments. Effects of increasing doses of gabapentin and pregabalin (i.t. and i.v.) on the withdrawal thresholds were analysed. These drugs were found to reduce tactile allodynia in a dose-dependent manner. In SCS non-responding rats, i.e. where stimulation per se failed to suppress allodynia, a combination of SCS and subeffective doses of the drugs markedly attenuated allodynia. In subsequent acute experiments, extracellular recordings from wide dynamic range neurones in the dorsal horn showed prominent hyperexcitability. The combination of SCS and gabapentin, at the same subeffective dose, clearly enhanced suppression of this hyperexcitability. In conclusion, electrical therapy and pharmacological therapy in neuropathic pain can, when they are inefficient individually, become effective when combined.

Topics: Acetates; Amines; Analgesics; Animals; Anticonvulsants; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electric Stimulation; Electrophysiology; Gabapentin; gamma-Aminobutyric Acid; Injections; Ischemia; Male; Mononeuropathies; Pain; Pain Management; Posterior Horn Cells; Pregabalin; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Spinal Cord; Touch

In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

Topics: Analgesics, Opioid; Animals; Chronic Disease; Colon; Colonic Diseases; gamma-Aminobutyric Acid; Hyperemia; Male; Morphine; Organ Size; Pain; Peroxidase; Pregabalin; Rats; Rats, Sprague-Dawley; Time Factors; Trinitrobenzenesulfonic Acid

The new anticonvulsants, gabapentin and pregabalin, are effective in the treatment of neuropathic pain. The sites and mechanisms of their analgesic action are not fully known. The authors have previously demonstrated that systemic gabapentin suppresses ectopic afferent discharges recorded from injured sciatic nerves in rats. In the current study, they further examined the stereospecific effect of pregabalin on neuropathic pain and afferent ectopic discharges in a rodent model of neuropathic pain.. Tactile allodynia and thermal hyperalgesia were induced by partial ligation of the left sciatic nerve in rats. Single-unit activity of afferent ectopic discharges was recorded from the sciatic nerve proximal to the site of ligation.. Intravenous injection of 10-30 mg/kg pregabalin dose-dependently attenuated tactile allodynia (n = 10) and thermal hyperalgesia (n = 8). The stereoisomer of pregabalin, R-3-isobutylgaba, had no analgesic effect in this dose range. Furthermore, intravenous injection of pregabalin, but not R-3-isobutylgaba, significantly inhibited the ectopic discharges from injured afferents in a dose-dependent manner (from 20.8 +/- 2.4 impulses/s during control to 2.3 +/- 0.7 impulses/s after treatment with 30 mg/kg pregabalin, n = 15). Pregabalin did not affect the conduction velocity of afferent fibers and the response of normal afferent nerves to mechanical stimulation.. These data strongly suggest that the analgesic effect of pregabalin on neuropathic pain is likely mediated, at least in part, by its peripheral inhibitory action on the impulse generation of ectopic discharges caused by nerve injury.

Topics: Animals; Anticonvulsants; Behavior, Animal; Electrophysiology; gamma-Aminobutyric Acid; Ligation; Male; Neurons, Afferent; Pain; Pain Measurement; Pain Threshold; Physical Stimulation; Pregabalin; Rats; Rats, Sprague-Dawley; Sciatic Neuropathy; Stereoisomerism

A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. In contrast, dynamic allodynia took almost twice as long to develop and was only present in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. However, neither of the compounds was effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.

Topics: Acetates; Amines; Amitriptyline; Analgesics; Animals; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Experimental; Gabapentin; gamma-Aminobutyric Acid; Hindlimb; Hyperglycemia; Injections; Injections, Spinal; Male; Morphine; Pain; Physical Stimulation; Pregabalin; Rats; Rats, Sprague-Dawley; Skin; Streptozocin; Touch

Gabapentin is an anticonvulsant that may represent a novel class of drugs, which has novel spinal antihyperalgesic activity. We sought to characterize this spinal action in a model of hyperalgesia that involves a mild thermal injury to the hind paw of the rat. Rats were prepared with chronic spinal catheters. Under brief halothane anesthesia, a thermal injury was induced by applying the left hind paw to a thermal surface (52.5 degrees C) for 45 s. This exposure results in mild erythema but no blistering. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus with which response latencies of the injured and uninjured (normal) paw could be obtained. Thirty minutes after thermal injury, the response latency in all groups decreased from 10-12 s to 5-7 s. Uninjured paw withdrawal latency was unaltered. The intrathecal injection of gabapentin (30-300 microg) produced a dose-dependent reversal of the hyperalgesia but had no effect on the response latency of the normal hind paw, even at the largest doses. A similar reversal was observed after intrathecal delivery of the structural analog S(+)-3-isobutyl gamma-aminobutyric acid (GABA) (30-300 microg), but not after the largest dose of its stereoisomer R(-)-3-isobutyl GABA (300 microg). The effects of both intrathecal gabapentin and S(+)-3-isobutyl GABA were reversed by intrathecal D-serine, but not L-serine. All effects were observed at doses that had no significant effect on motor function. These observations, in conjunction with the accumulating data on binding and transmitter release, emphasize that these gabapentinoids can selectively modulate the facilitation of spinal nociceptive processing otherwise generated by persistent small afferent input generated by tissue injury.. Gabapentin and its analog, 3-isobutyl gamma-aminobutyric acid, given spinally, produce a dose-dependent, D-serine-sensitive reversal of the thermal hyperalgesia evoked by mild thermal injury.

Topics: Acetates; Amines; Animals; Anticonvulsants; Burns; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Gabapentin; gamma-Aminobutyric Acid; Hyperalgesia; Injections, Spinal; Male; Pain; Pregabalin; Rats; Rats, Sprague-Dawley; Reflex; Serine; Stereoisomerism; Structure-Activity Relationship

Gabapentin (GP) has been shown to have antihyperalgesic properties and the site of drug action is reported to be the central nervous system. The goal of the present study was to determine whether GP also has a peripheral site of action. Rats received intraplantar 20-microl injections of 6, 60 or 600 microg GP + 2% formalin, 300 or 600 microg S-(+)-3-isobutylgaba + 2% formalin, 600 microg R-(-)-3-isobutylgaba + 2% formalin or formalin alone. The two lower doses of GP significantly reduced flinching and lifting/licking behavior during phase 2; however, phase 1 behaviors were unaffected, 600 microg GP significantly reduced these nociceptive behaviors during both phases. 600 microg S-(+)-3-isobutylgaba also reduced formalin-induced nociceptive behaviors; however, 600 microg of the isomer R-(-)-3-isobutylgaba had no effect. The antihyperalgesic effect of GP (1) was not due to a systemic effect since animals injected with 600 microg GP in one hindpaw and 2% formalin into the contralateral hindpaw developed nociceptive behaviors which were no different than those seen in animals injected with formalin alone; (2) was not due to a local anesthetic effect since needle sticks within the drug-injected region evoked paw withdrawal behavior which was not different from pre-drug levels; (3) was blocked by 20 microl D-serine but not by L-serine. Although the mechanism of action of GP has yet to be elucidated, these results indicate that GP has a peripheral site of action and thus may offer a novel therapeutic agent for topical or local treatment of pain of peripheral origin.

Topics: Acetates; Amines; Analgesics; Animals; Behavior, Animal; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Formaldehyde; Gabapentin; gamma-Aminobutyric Acid; Injections, Subcutaneous; Male; Nociceptors; Pain; Pain Measurement; Pregabalin; Rats; Rats, Sprague-Dawley; Serine