pregabalin and Chronic-Disease

Patients with POAG have lower corneal endothelial cell density than healthy controls of the same age. This may be attributed to mechanical damage from elevated IOP and toxicity of glaucoma medications.. Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.. T

Topics: Acetylcholine; Acinetobacter baumannii; Actinobacteria; Action Potentials; Adalimumab; Adaptation, Physiological; Adipates; Administration, Oral; Adolescent; Adrenal Glands; Adsorption; Adult; Aged; Aged, 80 and over; Aging; AIDS-Related Opportunistic Infections; Aldosterone; Amino Acids; Ammonia; Amoxicillin; AMP-Activated Protein Kinases; Animals; Antacids; Anti-Bacterial Agents; Antineoplastic Agents; Antirheumatic Agents; Apgar Score; Area Under Curve; ARNTL Transcription Factors; Arterial Pressure; Arthritis, Juvenile; Athletes; Attention; Biodegradation, Environmental; Biofilms; Biofuels; Biological Therapy; Biomass; Biomimetic Materials; Bioreactors; Birth Weight; Bismuth; Blood Flow Velocity; Bone and Bones; Brain Injuries, Traumatic; Calcium; Calcium Channels; Capsaicin; Carbon; Carcinoma, Hepatocellular; Cardiomegaly, Exercise-Induced; Cartilage; Cartilage, Articular; Case-Control Studies; Catalysis; Cats; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Death; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Charcoal; Chemokine CCL2; Child; Child, Preschool; Chondrogenesis; Chronic Disease; Circadian Clocks; Circadian Rhythm Signaling Peptides and Proteins; Clarithromycin; Coccidioides; Coccidioidomycosis; Cognitive Behavioral Therapy; Coinfection; Color; Coloring Agents; Computer Simulation; Computers, Molecular; Consensus; Corticosterone; Cyclic AMP Response Element-Binding Protein; Cytochrome P-450 Enzyme System; Death, Sudden, Cardiac; Density Functional Theory; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dialysis Solutions; Disease Models, Animal; Dogs; Dopamine Agonists; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Electrocardiography; Electrocardiography, Ambulatory; Electrolytes; Endocardium; Endocrine Disruptors; Endocytosis; Endoscopy, Gastrointestinal; Escherichia coli Proteins; Esters; Evolution, Molecular; Executive Function; Feasibility Studies; Female; Ferric Compounds; Fluorescence; Fluorescent Dyes; Fluorine Radioisotopes; Frailty; Free Radical Scavengers; Gabapentin; Geriatric Assessment; Glucaric Acid; Glucocorticoids; Glucose; Glucose Metabolism Disorders; Halogenated Diphenyl Ethers; Heart Rate; Heart Ventricles; HEK293 Cells; Helicobacter Infections; Helicobacter pylori; Hep G2 Cells; Hepatocytes; Humans; Hungary; Hydrogen Sulfide; Hydrogen-Ion Concentration; Immunologic Factors; Immunomodulation; Immunosuppressive Agents; Independent Living; Indocyanine Green; Infant; Infant Formula; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Inflorescence; Insulin Resistance; Insulins; International Agencies; Iron; Isotonic Solutions; Kidney Failure, Chronic; Kinetics; Lactones; Leukocytes, Mononuclear; Liver Neoplasms; Macular Edema; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetosomes; Male; Medical Audit; Mesenchymal Stem Cells; Metabolic Syndrome; Metformin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Molecular Conformation; Molecular Targeted Therapy; Motor Activity; Multiple Sclerosis; Mycophenolic Acid; Netherlands; Neuropsychological Tests; Nuclear Energy; Organs at Risk; Osteoarthritis; Osteoarthritis, Hip; Oxidation-Reduction; Palladium; Pericardium; Perinatal Death; Peritoneal Dialysis; Phantoms, Imaging; Pharmaceutical Preparations; Phospholipids; Phosphorylation; Physical Conditioning, Human; Physical Endurance; Pilot Projects; Polyketides; Polymers; Positron-Emission Tomography; Postoperative Period; Potassium; Powders; Pramipexole; Predictive Value of Tests; Pregabalin; Pregnancy; Pregnancy Outcome; Protein Structure, Secondary; Proton Pump Inhibitors; Puberty; Pulmonary Circulation; Quality Assurance, Health Care; Quantum Dots; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Rats, Sprague-Dawley; Receptors, CCR2; Receptors, Transferrin; Regeneration; Registries; Renal Insufficiency, Chronic; Reproducibility of Results; Research Design; Restless Legs Syndrome; Retina; Retinoid X Receptor alpha; Retrospective Studies; Rhenium; Risk Factors; RNA, Messenger; Severity of Illness Index; Sex Factors; Sodium; Sodium Fluoride; Solvents; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Stroke; Structure-Activity Relationship; Tachycardia, Ventricular; Tetracycline; Tetrahydrofolate Dehydrogenase; Tetrahydronaphthalenes; Thermodynamics; Thiophenes; Time Factors; Tinidazole; Tomography, Optical Coherence; Tomography, X-Ray Computed; Topiramate; Toxoplasma; Toxoplasmosis, Cerebral; Transferrin; Treatment Outcome; Up-Regulation; Upper Extremity; Uremia; Uveitis; Vascular Remodeling; Ventricular Fibrillation; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling; Verapamil; Veterans; Visual Acuity; Vitrectomy; Water Pollutants, Chemical; Zea mays; Zirconium

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

End-stage renal disease chronic itch is a frequent symptom that bothers patients with advanced stages of chronic kidney disease. The pathogenesis of the chronic itch symptom is complex and not yet fully understood and includes many metabolic, immunologic, and neurogenic factors. A significant burden of the disease results in decreased quality of life with sleep impairment, depressive symptoms, and increased mortality of affected individuals. No treatment of choice is available; topical therapy (emollients), phototherapy (UV-B), and systemic therapy (antiepileptics, opioid agonists, and antagonists) provide significant relief in varying percentages of patients.

Topics: Amines; Analgesics, Opioid; Anticonvulsants; Antipruritics; Chronic Disease; Cyclohexanecarboxylic Acids; Emollients; Gabapentin; gamma-Aminobutyric Acid; Humans; Kidney Failure, Chronic; Nalbuphine; Narcotic Antagonists; Pregabalin; Pruritus; Quality of Life; Renal Dialysis; Severity of Illness Index; Ultraviolet Therapy

There are few effective pharmacological therapies available to treat refractory chronic cough. Functional MRI studies of the brain have recently shown that patients with chronic cough have dysfunctional inhibitory control of cough. Self-management therapies delivered by physiotherapists or speech therapists are effective at suppressing cough. They enable patients to consciously suppress the urge to cough. The intervention consists of education, laryngeal hygiene, cough suppression and distraction measures and behaviour modification. The efficacy of Physiotherapy and Speech And Language Intervention (PSALTI) has been confirmed in two randomised control trials. In one trial, there was a 41% reduction in cough frequency with PSALTI, assessed objectively with the Leicester Cough Monitor, and a clinically significant improvement in quality of life. Importantly, the improvement in cough was sustained when therapy was discontinued. The addition of the Speech Pathology Treatment to neuromodulator drug therapy, Pregabalin has also been evaluated in a clinical trial. There was a clinically significant improvement in quality of life, and this was sustained when therapy was discontinued. The mechanism of action of PSALTI is not known and this should be investigated in future. Further studies are needed to identify the components of PSALTI that deliver the most benefit, and determine whether PSALTI is effective in cough associated with other chronic lung disorders.

Topics: Brain; Chronic Disease; Combined Modality Therapy; Cough; Humans; Language Therapy; Magnetic Resonance Imaging; Physical Therapy Modalities; Pregabalin; Quality of Life; Randomized Controlled Trials as Topic; Speech Therapy

Topics: Amines; Amitriptyline; Chronic Disease; Cough; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Neurotransmitter Agents; Practice Guidelines as Topic; Pregabalin

Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies.

Topics: Amines; Anti-Anxiety Agents; Chronic Disease; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Patient Satisfaction; Pregabalin; Pruritus; Quality of Life; Risk Assessment; Severity of Illness Index; Treatment Outcome

With anticonvulsant, anxiolytic, and analgesic properties, pregabalin has been evaluated for neuropathic pain and fibromyalgia (FM). These chronic conditions diminish patients' quality of life and increase healthcare utilization and costs.. To assess the current understanding of economic outcomes associated with pregabalin in neuropathic pain and FM.. Using keywords related to economic outcomes and pregabalin, we systematically searched MEDLINE- and EMBASE-indexed literature and nonindexed "grey" literature on neuropathic pain and FM published from March 2001 to October 2012. Included studies reported economic findings associated with pregabalin.. In the past 11 years, 55 publications assessed the direct costs, resource use, or cost-effectiveness of pregabalin for neuropathic pain and FM. Studies generally lacked comparability due to heterogeneous patient populations, assumptions, time periods, and geographies. In the US, following treatment initiation, pregabalin resulted in similar or higher levels of healthcare use for FM compared with duloxetine. In contrast, medical costs for neuropathic pain did not significantly differ after initiation of pregabalin vs. duloxetine or other standard therapies in the US, but in Spain and Sweden, retrospective database studies suggested that pregabalin was cost-saving vs. gabapentin. Few economic analyses estimated indirect costs.. Neuropathic pain and FM are associated with high healthcare resource use and costs. Economic studies of pregabalin in neuropathic pain and FM indicate some results favorable to other forms of care, but heterogeneity among study designs and populations hinder comparisons. Future economic analyses should aim to address data gaps regarding effects of pregabalin on productivity and resource use.

Topics: Amines; Analgesics; Anticonvulsants; Chronic Disease; Cost-Benefit Analysis; Cyclohexanecarboxylic Acids; Duloxetine Hydrochloride; Economics, Pharmaceutical; Fibromyalgia; Gabapentin; gamma-Aminobutyric Acid; Health Services; Humans; Neuralgia; Pregabalin; Quality of Life; Quality-Adjusted Life Years; Spain; Sweden; United States

Prurigo nodularis (PN) is a chronic, highly pruritic condition characterized by the presence of hyperkeratotic, excoriated, pruritic papules and nodules, with a tendency to symmetrical distribution. No reliable data exist about incidence and prevalence of PN in the general population, but it seems to be more frequent and more intense in females. PN may be associated with many dermatological and non-dermatological comorbidities, including psychiatric disease. Recent findings suggest a neuropathic origin of PN, with alterations in the dermal and epidermal small diameter nerve fibers. PN may have a tremendous impact on the quality of life, and few effective treatment options are available. Few randomized controlled trials (RCT) on the therapy of PN are available, demonstrating the efficacy of phototherapy alone or with psoralen, and of topical calcipotriol and topical steroids in occlusive medications. Thalidomide may be effective, but no RCT are available and its use is impractical due to the unfavorable safety profile. Gabapentin, pregabalin and the neurokinin receptor 1 antagonist, aprepitant, seem also to be effective in the therapy of PN, but RCTs are still lacking.

Topics: Amines; Chronic Disease; Cyclohexanecarboxylic Acids; Dermatologic Agents; Epidermis; Female; Gabapentin; gamma-Aminobutyric Acid; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Physical Therapy Modalities; Pregabalin; Prurigo; Sex Factors; Skin

Cost-effectiveness model from a Quebec societal perspective using meta-analyses of clinical trials.. To evaluate the cost-effectiveness of duloxetine in chronic low back pain (CLBP) compared with other post-first-line oral medications.. Duloxetine has recently received a CLBP indication in Canada. The cost-effectiveness of duloxetine and other oral medications has not previously been evaluated for CLBP.. A Markov model was created on the basis of the economic model documented in the 2008 osteoarthritis clinical guidelines of the National Institute for Health and Clinical Excellence. Treatment-specific utilities were estimated via a meta-analysis of CLBP clinical trials and a transfer-to-utility regression estimated from duloxetine CLBP trial data. Adverse event rates of comparator treatments were taken from the National Institute for Health and Clinical Excellence model or estimated by a meta-analysis of clinical trials in osteoarthritis using a maximum-likelihood simulation technique. Costs were developed primarily from Quebec and Ontario public sources as well as the published literature and expert opinion. The 6 comparators were celecoxib, naproxen, amitriptyline, pregabalin, hydromorphone, and oxycodone. Subgroup analyses and 1-way and probabilistic sensitivity analyses were performed.. In the base case, naproxen, celecoxib, and duloxetine were on the cost-effectiveness frontier, with naproxen the least expensive medication, celecoxib with an incremental cost-effectiveness ratio of $19,881, and duloxetine with an incremental cost-effectiveness ratio of $43,437. Other comparators were dominated. Key drivers included the rates of cardiovascular and gastrointestinal adverse events and proton pump inhibitor usage. In subgroup analysis, the incremental cost-effectiveness ratio for duloxetine fell to $21,567 for a population 65 years or older and to $18,726 for a population at higher risk of cardiovascular and gastrointestinal adverse events.. The model estimates that duloxetine is a moderately cost-effective treatment for CLBP, becoming more cost-effective for populations older than 65 years or at greater risk of cardiovascular and gastrointestinal events.. 1.

Topics: Age Factors; Aged; Amitriptyline; Analgesics; Cardiovascular Diseases; Celecoxib; Chronic Disease; Clinical Trials as Topic; Cost-Benefit Analysis; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Gastrointestinal Diseases; Humans; Hydromorphone; Low Back Pain; Markov Chains; Middle Aged; Models, Economic; Naproxen; Ontario; Osteoarthritis; Outcome Assessment, Health Care; Oxycodone; Pregabalin; Pyrazoles; Quality-Adjusted Life Years; Quebec; Sulfonamides; Thiophenes

The goal of this systematic review was to examine the evidence for the use of the neuromodulating agents, amitriptyline, gabapentin, pregabalin, and baclofen, in the management of chronic, idiopathic cough patients.. Online databases, including PubMed, Embase, Cochrane Review, and Web of Science, and publications cited in bibliographies were used.. Literature was searched by the 2 authors with a priori criteria for study selection.. Eight relevant articles were identified, including 2 randomized controlled trials, 2 prospective cohort or case-series designs with consecutive patients, 1 retrospective case series of consecutive patients, 1 retrospective case series whose consecutive status was not known, and 2 case reports of 6 and 2 patients, respectively. Improvements in cough-specific quality of life were noted in the randomized controlled trials. Cough severity was reduced in studies that measured this outcome measure. In the remaining studies, cough symptoms were less after neuromodulator treatment.. Benefit from neuromodulator treatment with amitriptyline, gabapentin, pregabalin, and baclofen in chronic, idiopathic cough patients was demonstrated. Further investigations using objective and subjective outcome measures are needed as well as studies exploring optimal dose, length of treatment, and relapse rates posttreatment.

Topics: Amines; Amitriptyline; Baclofen; Chronic Disease; Cough; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Neurotransmitter Agents; Pregabalin; Quality of Life

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a condition that is detrimental to the quality of life of men. Evidence suggests that it may have a neuropathic origin and therefore medications such as pregabalin might have a role in the controlling of symptoms.. The primary objective was to compare pregabalin to other modalities of pain relief to alleviate men's symptoms of CP/CPPS.The secondary objective was to assess the safety and effectiveness of pregabalin to improve various individual symptoms consistent with CP/CPPS.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to May 2012), EMBASE (1980 to May 2012), CINAHL, clinicaltrials.gov, Google Scholar, and reference lists of articles and abstracts from conference proceedings, without language restriction for pregabalin treatment of Class III prostatitis and CP/CPPS.. Randomized controlled trials (RCTs) comparing pregabalin to placebo or other types of analgesics for the management of patients with CP/CPPS were included. Patients with known causes of pain/discomfort were excluded.. Only one RCT was included. The trial compared pregabalin to placebo for patients who had CP/CPPS.. For men who responded clinically (≥ 6-point improvement), there was no difference between the pregabalin (103/218; 47.2%) and placebo (38/106; 35.8%) arms (risk ratio (RR) 1.32; 95% CI 0.99 to 1.76). There was less pain with a higher point improvement in the pregabalin group compared to the placebo group (4.2 points versus 1.7 points, respectively; mean difference (MD) -2.3 points; 95% CI -4.0 to -0.7 points).Though 59% (191/324) of the patients developed side effects, no serious effects were experienced. There were significantly more neurologic side effects in the pregabalin group compared to the placebo group (38.5% (84/218) versus 22.6% (24/106), respectively; RR 1.7; 95% CI 1.15 to 2.51), and less pain in the pregabalin group than in the placebo group (17.4% (38/218) versus 33.3% (35/106), respectively; RR 0.53; 95% CI 0.36 to 0.78). However, no significant differences were seen between the pregabalin and placebo groups with regards to gastrointestinal disturbances (18.3% (40/218) versus 18.9% (20/106), respectively; RR 0.97; 95% CI 0.60 to 1.58), ocular/visual symptoms (6.9% (15/218) versus 2.8% (3/106), respectively; RR 2.43; 95% CI 0.72 to 8.22), and renal/genitourinary symptoms (5.5% (12/218) versus 1.9% (2/106), respectively; RR 3.03; 95% CI 0.67 to 13.79).. There is evidence from one RCT that pregabalin does not improve CP/CPPS symptoms and causes adverse effects in a large percentage of men. However, research is required to assess further whether pregabalin has a role in patients with CP/CPPS for symptom control.

Topics: Analgesics; Chronic Disease; gamma-Aminobutyric Acid; Humans; Male; Pelvic Pain; Pregabalin; Prostatitis; Randomized Controlled Trials as Topic

Recent literature points to postviral sensory neuropathy as a possible cause for refractory chronic cough. Vagal neuropathy may affect the sensory branches, inducing chronic cough or laryngospasm. Although the clinical presentation is fairly well described, there is little in the way of diagnostic criteria to establish this diagnosis. This article highlights the clinical picture of this disease and the efficacy, side-effect profiles of the currently used pharmacological interventions.

Topics: Adrenergic Uptake Inhibitors; Amines; Amitriptyline; Anticonvulsants; Chronic Disease; Cough; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Pregabalin; Vagus Nerve Diseases; Virus Diseases

Multimodal postoperative pain management targeted at diminishing harmful outcomes should include pregabalin in cases that need opioid reduction and when the risk of developing chronic neuropathic postsurgical pain is present. Gabapentanoids have grown in importance due to their opioid-sparing effects. They may also contribute to the prevention of chronic postsurgical pain.. We reviewed the literature regarding the use of gabapentanoids and their role in treatment modalities in acute postsurgical pain. Dosing, therapeutic efficacy, side effects, and their role within a multimodal regimen are discussed. Particular emphasis is placed on their ability to provide an opioid-sparing effect, as well as on their potential for inhibiting chronic neuropathic pain. A Pubmed search of pregabalin, gabapentin, acute pain, multimodal analgesia, chronic postsurgical pain, and neuropathic pain between 2000 and 2010 was done. Relevant articles - including randomized controlled trials, retrospective trials, case series, case reports, and review articles - were filtered to include those that relate to postsurgical pain.. Readers will gain an increased appreciation of the role of pregabalin in postsurgical pain in patients at risk of developing chronic pain.. Pregabalin is a safe and effective medication that may decrease perioperative opioid use in patients with more acute neuropathic pain than acute inflammatory pain. When surgery involves more neuropathic-type acute pain there is growing evidence that pregabalin may decrease the incidence of chronic pain.

Topics: Acute Disease; Analgesics; Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain, Postoperative; Pregabalin

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

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

Neuropathic pain has been known to be refractory to traditional analgesics, such as opioids and non-steroidal anti-inflammatoy drugs. Some mechanisms of the development of neuropathic pain have been proposed; 1) sprouting of A beta fibers to the superficial layer of the dorsal horn, 2) ectopic discharge in the dorsal root ganglion and/or in neuroma at the nerve stump, 3) spinal sensitization. Ectopic discharge has been reported to be inhibited by Na+ channel blocker, such as lidocaine, and anticonvulsant. Lidocaine and anticonvulsant are used in the management of neuropathic pain. Activation of NMDA receptor is usually involved in the development of spinal sensitization and NMDA receptor antagonist, such as ketamine, is used in the management of neuropathic pain. Recently, alpha2delta subunit blocker, new class of anticonvulsant, is introduced to the management of neuropathic pain. alpha2delta subunit is the subunit of Ca2+ channel and modulate the influx of Ca2+. This Ca2+ influx induces release of neurotransmitter in the neuron. alpha 2 delta subunit blockers, such as gabapentin and pregabalin, may reduce the release of neurotransmitter and elicit analgesic effect in the treatment of neuropathic pain.

Topics: Amines; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents, Tricyclic; Calcium Channel Blockers; Chronic Disease; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Ketamine; Leprosy; Lidocaine; Neuralgia; Posterior Horn Cells; Pregabalin; Receptors, N-Methyl-D-Aspartate; Sodium Channel Blockers

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

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

Chronic refractory cough (CRC) is a difficult problem to treat. Speech pathology treatment (SPT) improves symptoms but resolution is incomplete. Centrally acting neuromodulators also improve cough symptoms, but not cough reflex sensitivity, and the effect is short-lived. We hypothesized that combined SPT and centrally acting neuromodulators would have a superior outcome than SPT alone. Our goal was to determine whether combined pregabalin and SPT is more effective than SPT alone.. Randomized placebo controlled trial. Forty patients with CRC were randomly assigned to receive either combined SPT and pregabalin 300 mg daily or combined SPT and placebo. Outcome measures were collected at baseline, end of treatment, and 4 weeks after the end of treatment. Primary outcome measures were cough frequency using the Leicester Cough Monitor, cough severity using a visual analog scale (coughVAS), and cough-related quality of life (QOL) using the Leicester Cough Questionnaire (LCQ).. Cough severity, cough frequency, and cough QOL improved in both groups. The degree of improvement in LCQ and coughVAS was greater with combined SPT and pregabalin than SPT alone; the mean difference in LCQ was 3.5, 95%CI of difference 1.1 to 5.8; the mean difference in coughVAS was 25.1, 95% CI of difference 10.6 to 39.6. There was no significant difference in improvement in cough frequency between groups. There was no deterioration in symptoms once pregabalin was withdrawn. Median capsaicin cough sensitivity improved from 15.7 to 47.5 μM with combined SPT and pregabalin and from 3.92 to 15.7 μM with SPT alone.. Combined SPT and pregabalin reduces symptoms and improves QOL compared with SPT alone in patients with CRC.

Topics: Aged; Analgesics; Chronic Disease; Combined Modality Therapy; Cough; Double-Blind Method; Female; Humans; Male; Middle Aged; Pregabalin; Quality of Life; Severity of Illness Index; Speech-Language Pathology; Surveys and Questionnaires; Treatment Outcome

There is no head on comparison of amitriptyline (AMT) and pregabalin (PG) in relieving pain and disability in chronic low backache (CLBA). This randomized controlled trial reports the efficacy and safety of AMT and PG in CLBA.. Patients with CLBA, 15-65 years of age without specific cause and significant neurological deficit were included. Severity of pain was assessed by Visual Analogue Scale (VAS) and disability by Oswestry Disability Index (ODI). Patients were followed up at 6 and 14 weeks and their VAS score, ODI and side effect were noted. Primary outcome was pain relief (>50% improvement in VAS score) at 14 weeks and secondary outcome were reduction in ODI (>20%) and side effects.. 200 patients with CLBA were randomized to AMT (n=103) and PG (n=97) using random numbers. The VAS score and ODI improved significantly following AMT and PG at 6 and 14 weeks compared to baseline. The improvement in pain (57.3% Vs 39.2%; P=0.01) and disability (65% Vs 49.5%; P=0.03) however was more in AMT group. The composite side effects were similar in both groups.. AMT and PG are effective in CLBA but AMT reduced pain and disability significantly compared to PG.

Topics: Adolescent; Adult; Aged; Amitriptyline; Analgesics, Non-Narcotic; Chronic Disease; Disability Evaluation; Female; gamma-Aminobutyric Acid; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Pregabalin; Treatment Outcome; Young Adult

Uremic pruritus (UP) affects many patients suffering from chronic kidney disease (CKD) and has a negative impact on quality of life and survival. It has become increasingly evident that central transmission and sensitization processes similar to those observed in chronic pain are important mechanisms of pruritus.. To test the potential role of pregabalin in reducing the intensity of UP in CKD patients.. We prospectively collected data on CKD patients who suffered from severe intractable pruritus. Patients were asked to record the intensity of pruritus on a visual analogue scale.. Twelve patients were studied. The average pretreatment pruritus score was 9.7 ± 0.9 and decreased to 3.7 ± 2.35, 3.2 ± 1.75, and 3 ± 1.5 after one, four, and 24 weeks of treatment, respectively (P < 0.05). The positive effect of pregabalin was demonstrated during the first week of therapy in six patients. Most patients required 25mg a day. Pregabalin was well tolerated, with somnolence and dizziness developing in two patients.. We demonstrated dramatic improvement of long-standing UP after the initiation of pregabalin. We suggest that pregabalin can be used safely in CKD but careful titration of the dose is required to obtain an optimal response and minimize the possible adverse effects.

Topics: Aged; Analgesics; Anticonvulsants; Chronic Disease; Female; gamma-Aminobutyric Acid; Humans; Male; Pregabalin; Pruritus; Renal Insufficiency, Chronic; Treatment Outcome; Uremia

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

Despite the enormous success of total knee arthroplasty (TKA), chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. We hypothesized that perioperative treatment with pregabalin, a chronic pain medication, would reduce the incidence of postsurgical neuropathic pain.. We performed a randomized, placebo-controlled, double-blind trial of pregabalin (300 mg) administered before TKA and for 14 days after TKA (150-50 mg twice daily). Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale. Secondary outcomes included postsurgical recovery and rehabilitation measures, including knee range of motion, opioid consumption, postoperative pain scores, sleep disturbance, and time to discharge as well as the occurrence of postoperative systemic complications.. Of the 240 patients randomly assigned to the 2 treatment groups (120 in each), data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients. At both 3 and 6 mo postoperatively, the incidence of neuropathic pain was less frequent in the pregabalin group (0%) compared with the placebo group (8.7% and 5.2% at 3 and 6 mo, respectively; P = 0.001 and P = 0.014). Patients receiving pregabalin also consumed less epidural opioids (P = 0.003), required less oral opioid pain medication while hospitalized (P = 0.005), and had greater active flexion over the first 30 postoperative days (P = 0.013). There were no differences in the actual recorded duration of hospitalization between the 2 groups, although time to achieve hospital discharge criteria was longer for placebo patients, 69.0 +/- 16.0 h (mean +/- SD), than that of pregabalin patients, 60.2 +/- 15.8 h (P = 0.001). Sedation (P = 0.005) and confusion (P = 0.013) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin.. Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA, with less opioid consumption and better range of motion during the first 30 days of rehabilitation. However, in the doses tested, it is associated with a higher risk of early postoperative sedation and confusion.

Topics: Aged; Analgesics; Anesthesia, Epidural; Arthroplasty, Replacement, Knee; Chronic Disease; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Peripheral Nervous System Diseases; Pregabalin; Prospective Studies; Range of Motion, Articular; Sleep; Treatment Outcome

This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin (PGB) as mono- or add-on therapy in one of two treatment options. Patients with a pain score of > or =4, refractory to usual care for neuropathic pain for at least 6 months, were allocated consecutively to one of two treatment strategies according to the decision of the physician: complete switch to a flexible-dosage, monotherapeutic or add-on therapy with pregabalin (PGB group), or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin (non-PGB group). After 4 weeks (primary endpoint) a significant improvement in pain reduction was documented in both intention-to treat (ITT) analysis (PGB group, n = 85: mean pain score reduction of 3.53, SD 2.03, p < 0.001; non-PGB group, n = 102; mean pain score reduction of 2.83, SD 2.23, p < 0.001) and per-protocol (PP) analysis (PGB group, n = 79: mean pain score reduction 3.53 vs. 2.83, p < 0.05; non-PGB group, n = 81; 3.5 vs. 2.9, p < 0.05) compared to baseline. Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction. These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Chronic Disease; Cohort Studies; Drug Prescriptions; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Peripheral Nervous System Diseases; Pregabalin; Product Surveillance, Postmarketing; Treatment Failure

Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic.. This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed.. Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups.. Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS.. clinicaltrials.gov Identifier: NCT00371033.

Topics: Adult; Aged; Analgesics; Canada; Chronic Disease; Double-Blind Method; gamma-Aminobutyric Acid; Hospitals, University; Humans; Male; Middle Aged; Pelvic Pain; Pregabalin; Prostatitis; Treatment Outcome; United States

The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms.. In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0-100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment.. Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy.. Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects.

Topics: Adult; Aged; Analgesics; Celecoxib; Chronic Disease; Cyclooxygenase 2 Inhibitors; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Pregabalin; Pyrazoles; Single-Blind Method; Sulfonamides; Treatment Outcome

Pain intensity is frequently measured on an 11-point pain intensity numerical rating scale (PI-NRS), where 0=no pain and 10=worst possible pain. However, it is difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1- or 2-point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies. We have estimated a clinically important difference on this scale by relating it to global assessments of change in multiple studies of chronic pain. Data on 2724 subjects from 10 recently completed placebo-controlled clinical trials of pregabalin in diabetic neuropathy, postherpetic neuralgia, chronic low back pain, fibromyalgia, and osteoarthritis were used. The studies had similar designs and measurement instruments, including the PI-NRS, collected in a daily diary, and the standard seven-point patient global impression of change (PGIC), collected at the endpoint. The changes in the PI-NRS from baseline to the endpoint were compared to the PGIC for each subject. Categories of "much improved" and "very much improved" were used as determinants of a clinically important difference and the relationship to the PI-NRS was explored using graphs, box plots, and sensitivity/specificity analyses. A consistent relationship between the change in PI-NRS and the PGIC was demonstrated regardless of study, disease type, age, sex, study result, or treatment group. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI-NRS represented a clinically important difference. The relationship between percent change and the PGIC was also consistent regardless of baseline pain, while higher baseline scores required larger raw changes to represent a clinically important difference. The application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Chronic Disease; Controlled Clinical Trials as Topic; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Low Back Pain; Male; Middle Aged; Neuralgia; Osteoarthritis; Pain Measurement; Pregabalin; Treatment Outcome

Patients with chronic cough (>8 weeks) often remain symptomatic after appropriate investigations and therapeutic trials. Prior research has shown a benefit in certain individuals from pregabalin, but clinical improvement is quite unpredictable and variable.. The main objective of this study was to identify the demographic and clinical characteristics associated with a higher likelihood of cough improvement with a trial of pregabalin therapy.. 50 consecutive patients with chronic cough were enrolled in this prospective cohort study. Subjects were prescribed pregabalin 75 mg oral qhs for 4 weeks followed by 75 mg oral bid. Leicester Cough Questionnaire (LCQ) was completed at treatment initiation and after 3 months of therapy. A comparison was performed between treatment responders (LCQ total score improvement ≥1.3) and non-responders.. 56% of patients reported a LCQ total score improvement ≥1.3 (minimal clinically important difference). Responders to pregabalin therapy were more likely to have refractory (with underlying pulmonary disease) versus unexplained chronic cough (p = 0.01). Patients with significant improvement were also on average more symptomatic at baseline (mean LCQ total score 10.2 versus 13.0, p < 0.01). No significant relationship was identified with age, gender, body mass index, history of anxiety and/or depression, cigarette smoking history, or cough duration (p > 0.05). The unexplained chronic cough group had a strong female predominance (85.7% versus 40.9% for refractory cough, p < 0.01).. This is the first study that has investigated clinical predictors of treatment response to pregabalin in chronic cough patients. Further research is needed to develop therapies for subjects who do not improve with currently available neuromodulating medications.

Topics: Chronic Disease; Cough; Female; Humans; Male; Pregabalin; Prospective Studies; Quality of Life; Surveys and Questionnaires

Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy.. We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain.. Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation.. These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.

Topics: Administration, Ophthalmic; Analgesics; Animals; Astrocytes; Calcium Channels, L-Type; Chronic Disease; Cornea; Disease Models, Animal; Dry Eye Syndromes; Eye Pain; Hyaluronic Acid; Hyperalgesia; Male; Microglia; Neuralgia; Neurons; Ophthalmic Solutions; Pregabalin; Rats; Rats, Sprague-Dawley; Trigeminal Nerve

Topics: Adult; Air Pollution, Indoor; Antifungal Agents; Antitussive Agents; Chronic Disease; Coriolaceae; Cough; Drug Interactions; Female; Humans; Hypersensitivity; Itraconazole; Male; Medically Unexplained Symptoms; Middle Aged; Mycoses; Pregabalin; Sensation; Skin Tests; Sputum

Chronic refractory cough (CRC) is a common clinical problem which is more likely associated with some physical problems. Although many patients have received satisfactory treatment, there were still many patients suffered from long-term cough symptoms after standardized treatment.. A patient suffered from postherpetic neuralgia (PHN) and also he complained CRC for more than 20 years.. The patient was diagnosed with PHN and CRC.. Pregabalin was originally administered to treat PHN.. pregabalin not only alleviated her pain of PHN but also relieved chronic cough.. This report demonstrated the surprising effect of pregabalin on the treatment of CRC.

Topics: Analgesics; Chronic Disease; Cough; Female; Humans; Middle Aged; Neuralgia, Postherpetic; Pregabalin; Treatment Outcome

Zolpidem is an imidazopyridine nonbenzodiazepine hypnotic drug with a high affinity to the α1 subunit of the gamma amino butyric acid A receptor It is the first pharmacological option in the short-term management of sleep-onset insomnia. Initially considered a safer drug compared to benzodiazepines because of lower liability for abuse and dependence, recently, an increasing body of reports has questioned zolpidem's proneness to misuse. In this report, we describe a case of serious zolpidem abuse requiring pharmacological washout during hospitalization because of previous withdrawal seizures in a patient with chronic sleep-onset and maintenance insomnia.

Topics: Aged; Anticonvulsants; Chronic Disease; Clonazepam; Female; Hospitalization; Humans; Levetiracetam; Pregabalin; Seizures; Selective Serotonin Reuptake Inhibitors; Sertraline; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Zolpidem

Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain. L-Acetylcarnitine-induced analgesia persisted for at least 14 days after drug withdrawal. In contrast, the analgesic effect of pregabalin, amitryptiline, ceftriaxone, and N-acetylcysteine disappeared seven days after drug withdrawal. L-acetylcarnitine treatment enhanced mGlu2/3 receptor protein levels in the dorsal region of the spinal cord. This effect also persisted for two weeks after drug withdrawal and was associated with increased levels of acetylated histone H3 bound to the Grm2 gene promoter in the dorsal root ganglia. A long-lasting analgesic effect of L-acetylcarnitine was also observed in mice subjected to chronic constriction injury of the sciatic nerve. In these animals, a 14-day treatment with pregabalin, amitryptiline, tramadol, or L-acetylcarnitine produced a significant antiallodynic effect, with pregabalin displaying the greatest efficacy. In mice treated with pregabalin, tramadol or L-acetylcarnitine the analgesic effect was still visible 15 days after the end of drug treatment. However, only in mice treated with L-acetylcarnitine analgesia persisted 37 days after drug withdrawal. This effect was associated with an increase in mGlu2/3 receptor protein levels in the dorsal horns of the spinal cord. Conclusions Our findings suggest that L-acetylcarnitine has the unique property to cause a long-lasting analgesic effect that might reduce relapses in patients suffering from chronic pain.

Topics: Acetylcarnitine; Amitriptyline; Analgesics; Animals; Chronic Disease; Disease Models, Animal; Epigenesis, Genetic; Freund's Adjuvant; Hyperalgesia; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuralgia; Pain Management; Pregabalin; Receptors, Metabotropic Glutamate; Time Factors; Tramadol

Talking is a significant trigger for cough in patients with chronic cough; however, the stimulus required to trigger cough has not been quantified. The aim of this study was to examine the effect of a vocal loading task on phonation and cough behavior in patients with chronic cough and identify change following therapy.. This is a prospective observational study.. This study involved 33 patients with chronic cough. Participants were assessed with the lingWAVES Vocal Loading Test protocol before and after intervention for chronic cough.. At baseline, almost 40% of patients had impaired vocal function and were unable to complete the vocal loading test. This improved following therapy, with 94% of patients being able to complete the test at follow-up. There was difficulty maintaining phonation, with 60% of the task unvoiced at baseline. This improved following therapy. The vocal loading test triggered coughing in 58% of patients; however, this improved following intervention. Acoustic measures during the vocal loading test did not change following therapy.. Phonation is an important trigger for cough. Patients with chronic cough demonstrated impaired performance on tests of vocal loading. Most parameters improved following therapy.

Topics: Acoustics; Aged; Chronic Disease; Cough; Female; Humans; Larynx; Male; Middle Aged; Phonation; Pregabalin; Prospective Studies; Randomized Controlled Trials as Topic; Sound Spectrography; Speech Acoustics; Speech Production Measurement; Time Factors; Treatment Outcome; Voice Disorders; Voice Quality

DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azepines; Carbolines; Chronic Disease; Constriction, Pathologic; Inflammation; Mice; Molecular Structure; Neuralgia; Pain Measurement; Rats; Spinal Nerves

Topics: Adult; Aged; Antipruritics; Chronic Disease; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Pruritus; Republic of Korea

Topics: Acute Disease; Analgesics; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Controlled Clinical Trials as Topic; Early Ambulation; gamma-Aminobutyric Acid; Humans; Iatrogenic Disease; Low Back Pain; Magnetic Resonance Imaging; Neuralgia; Pregabalin; Time Factors

We investigated the effects of gabapentin and pregabalin on the itch-associated response in a mouse model of chronic dermatitis induced by the repeated application of 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone). Challenging the mice with oxazolone-induced chronic dermatitis with the oxazolone evoked severe and transient scratching behavior until 1 h after the application of oxazolone. Thereafter, a more mild and continuous scratching behavior was also observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by systemic injection of gabapentin and pregabalin. This effect of these compounds was correlated with its affinity for the α₂δ subunit of voltage-gated Ca²(+) channels. Intrathecal injection, but not peripheral treatment, with gabapentin inhibited the scratching behavior in this model. Gabapentin failed to suppress the scratching behavior induced by the intradermal injection of compound 48/80 in normal mice. The expression of the α₂δ-1 subunit in dorsal root ganglion (DRG) from mice following repeated application of oxazolone was significantly higher than that from normal mice. These results suggest that gabapentin and pregabalin show an anti-pruritic activity through α₂δ-subunit binding, and the up-regulation of the α₂δ-1 subunit in DRG may therefore play an important role in its anti-pruritic activity.

Topics: Amines; Animals; Calcium Channels; Chronic Disease; Cyclohexanecarboxylic Acids; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Eruptions; Gabapentin; gamma-Aminobutyric Acid; Ganglia, Spinal; Injections, Spinal; Male; Mice; Mice, Inbred BALB C; Oxazolone; Pregabalin; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Time Factors; Up-Regulation; Urticaria

Glossopharyngeal neuralgia is a rare condition and the origin is mostly idiopathic. Causes of symptomatic glossopharyngeal neuralgia can be tumors, infarction or trauma. We report the case of a 28-year-old patient who developed glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma, which is an extremely rare tumor. Treatment consisted of orally administered pregabalin and a series of injections of buprenorphine in the superior cervical ganglion (ganglionic local opioid application/analgesia, GLOA) which led to a substantial decrease in the frequency of pain attacks. This improvement was maintained at 1-year follow-up. This is the first report of development of glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma.

Topics: Administration, Oral; Adult; Analgesics; Analgesics, Opioid; Autonomic Nerve Block; Buprenorphine; Chronic Disease; Female; gamma-Aminobutyric Acid; Glossopharyngeal Nerve; Glossopharyngeal Nerve Diseases; Humans; Injections; Magnetic Resonance Imaging; Neurilemmoma; Pain Measurement; Pain, Postoperative; Pregabalin; Superior Cervical Ganglion

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

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

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

Topics: Aged; Anticonvulsants; Bumetanide; Chronic Disease; gamma-Aminobutyric Acid; Heart Failure; Herpes Zoster; Humans; Male; Neuralgia, Postherpetic; Pregabalin; Treatment Outcome; Weight Gain

This prospective, open-label study aimed to evaluate the efficacy of pregabalin treatment in patients suffering from trigeminal neuralgia with and without concomitant facial pain. Fifty-three patients with trigeminal neuralgia (14 with concomitant chronic facial pain) received pregabalin (PGB) 150-600 mg daily and were prospectively followed for 1 year. The primary outcome was number of patients pain free or with reduction of pain intensity by > 50% and of attack frequency by > 50% after 8 weeks. Secondary outcome was sustained pain relief after 1 year. Thirty-nine patients (74%) improved after 8 weeks with a mean dose of 269.8 mg/day (range 150-600 mg/day) PGB: 13 (25%) experienced complete pain relief and 26 (49%) reported pain reduction > 50%, whereas 14 (26%) did not improve. Patients without concomitant facial pain showed better response rates (32 of 39, 82%) compared with patients with concomitant chronic facial pain (7 of 14, 50%, P = 0.020). Concomitant chronic facial pain appears to be a clinical predictor of poor treatment outcome. PGB appears to be effective in the treatment of trigeminal neuralgia.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Chronic Disease; Dose-Response Relationship, Drug; Facial Pain; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Prospective Studies; Time Factors; Treatment Outcome; Trigeminal Neuralgia

Topics: Anticonvulsants; Chronic Disease; gamma-Aminobutyric Acid; Humans; Pregabalin; Pruritus

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

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 idiopathic singultus (hiccup) is a debilitating condition affecting mostly elderly males. While in the past, pharmacologic singultus treatment was mostly "trial and error," more recently, treatment has become both more evidence based and pathophysiology guided. A combination of an acidity-reducing drug (H(2)-receptor blocker or proton pump inhibitor) with baclofen (gamma-amino-butyric-acid receptor type B agonist) has become the most widely used regimen. Some clinicians replace or supplement baclofen with gabapentin. We present three cases of chronic idiopathic hiccup managed with gabapentin or another alpha-2-delta ligand, pregabalin. This is the first reported use of pregabalin for this indication.

Topics: Aged; Amines; Anticonvulsants; Calcium Channels; Chronic Disease; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Hiccup; Humans; Ligands; Male; Middle Aged; Pregabalin

Pregabalin, a 3-substituted analogue of gamma-amino butyric acid has recently been approved for treatment of neuropathic pain. We have investigated the anatomical binding profile of [(3)H] pregabalin following chronic constriction injury (CCI) and compared this with alpha 2 delta 1 subunit expression using in situ hybridisation. We report here that the intensity and distribution pattern of [(3)H] pregabalin binding is altered in the ipsilateral dorsal horn following CCI and this is associated with a corresponding increase in alpha 2 delta 1 mRNA in the ipsilateral dorsal root ganglion (DRG). It is likely that increased DRG mRNA production leads to increased alpha 2 delta 1 protein production and subsequent transport by primary afferents to the dorsal horn. The increased expression of calcium channel subunits and protein in central terminals is interesting, given that abnormal activity within sensory nerves is likely to significantly contribute to the symptomatology of neuropathic pain. The upregulation of pregabalin binding sites in sensory nerve terminals may occur as part of the response to nerve damage in neuropathic pain patients, and therefore, preferential actions of pregabalin at these sites may contribute to its mechanism of action in man.

Topics: Afferent Pathways; Analgesics; Animals; Binding, Competitive; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Chronic Disease; Denervation; gamma-Aminobutyric Acid; Ganglia, Spinal; Ligation; Male; Neuralgia; Neurons, Afferent; Neuropeptides; Nociceptors; Peripheral Nervous System Diseases; Posterior Horn Cells; Pregabalin; Radioligand Assay; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tritium

Topics: Aged; Amines; Anti-Ulcer Agents; Anticonvulsants; Chronic Disease; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Hiccup; Humans; Male; Omeprazole; Pregabalin; Recurrence

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

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: 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: Algorithms; Analgesics; Anticonvulsants; Back Pain; Chronic Disease; Cross-Sectional Studies; Diagnosis, Differential; Drug Therapy, Combination; gamma-Aminobutyric Acid; Humans; Pregabalin; Radiculopathy

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

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

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