pregabalin and Diabetes-Mellitus--Type-2

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

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Diabetes is a worldwide epidemic, and associated neuropathy is its most costly and disabling complication. Given the rising prevalence of painful diabetic neuropathy, it is increasingly important that we understand the best ways to diagnose and treat this condition. Diagnostic tests in this field are evolving rapidly. These include the use of skin biopsies to measure small unmyelinated fibers, as well as even newer techniques that can measure both small unmyelinated fibers and large myelinated fibers in the same biopsy. The main treatments for painful diabetic neuropathy remain management of the underlying diabetes and drugs for the relief of pain. However, emerging evidence points to major differences between type 1 and type 2 diabetes, including the ability of glycemic control to prevent neuropathy. Enhanced glucose control is much more effective at preventing neuropathy in patients with type 1 diabetes than in those with type 2 disease [corrected]. This dichotomy emphasizes the need to study the pathophysiologic differences between the two types of diabetes, because different treatments may be needed for each condition. The impact of the metabolic syndrome on neuropathy in patients with type 2 diabetes may account for the difference between the two types of diabetes and requires further study. Finally, neuropathic pain is under-recognized and undertreated despite an ever evolving list of effective drugs. Evidence exists to support several drugs, but the optimal sequence and combination of these drugs are still to be determined.

Topics: Amines; Analgesics; Analgesics, Opioid; Biopsy; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; gamma-Aminobutyric Acid; Humans; Hypoglycemic Agents; Pregabalin; Sensory Thresholds; Skin; Thiophenes; Touch Perception

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

Diabetic peripheral polyneuropathy is the most common chronic complication of type 2 diabetes. Neuropathic pain is challenging to manage, and various drugs are required to control it, decreasing treatment adherence. Pregabalin, a ligand that binds to alpha-2-delta subunits of the presynaptic calcium channel, has been approved by the Food and Drug Administration for the treatment of diabetic neuropathic pain. In this study, we will compare the efficacy, safety, treatment satisfaction, and compliance between pregabalin sustained-release (SR) tablets and pregabalin immediate-release (IR) capsules in type 2 diabetic patients with peripheral neuropathic pain.. This study is a randomized, active-controlled, parallel, open-label, multicenter, phase 4 clinical trial (trial registration NCT05624853). Type 2 diabetic patients with glycosylated hemoglobin below 10% and peripheral neuropathic pain who have been taking pregabalin 150 mg/d or more for more than 4 weeks will be randomly assigned to pregabalin SR tablet (150 mg once a day, n = 65) or pregabalin IR capsule (75 mg twice a day, n = 65) therapy for 8 weeks. The primary outcome will be the efficacy of SR pregabalin after 8 weeks of treatment, which will be assessed by visual analog scale measurements. The secondary outcomes will include changes in several parameters, such as quality of life, treatment satisfaction, quality of sleep, and drug compliance.. In thus study, we aim to demonstrate that pregabalin SR tablets are associated with better compliance and satisfaction compared with pregabalin IR capsules, despite similar efficacy.

Topics: Analgesics; Capsules; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Humans; Neuralgia; Pregabalin; Quality of Life; Tablets; Treatment Outcome

The trial aimed to investigate the effectiveness of exogenous melatonin as an adjuvant to pregabalin for relief of pain in patients suffering from painful diabetic neuropathy (PDN).. This randomized, double-blind, placebo-controlled trial was carried out between October 2019 and December 2020 in an outpatient specialty clinic in Iran. One-hundred-three type 2 diabetic patients suffering from PDN were randomized into either the melatonin group (n = 52) or the placebo group (n = 51). Besides pregabalin at a dose of 150 mg per day, patients started with melatonin or an identical placebo, at a dose of 3 mg/day at bedtime for 1 week, which was augmented to 6 mg/day for further 7 weeks. The primary outcomes were changes in mean NRS (numerical rating scale) pain score from baseline to endpoint and responder rate (patients with a reduction of 50% and higher in average pain score compared with baseline). Secondary endpoints were changes in mean NRS pain-related sleep-interference score, overall improvement evaluated by Patient and Clinical Global Impressions of Change (PGIC, CGIC), and impact of the intervention on patient's Health-related quality of life (QOL). All analyses were conducted on an Intention-to-Treat (ITT) analysis data set.. At the study endpoint, treatment with melatonin resulted in a considerably higher reduction in the mean NRS pain score in comparison with placebo (4.2 ± 1.83 vs. 2.9 ± 1.56; P-value < 0.001). In terms of treatment responders, a greater proportion of melatonin-treated patients satisfied the responder criterion than placebo-treated patients (63.5% vs. 43.1%). Melatonin also reduced pain-related sleep interference scores more than did placebo (3.38 ± 1.49 vs. 2.25 ± 1.26; P-value < 0.001). Further, at the endpoint, more improvement was also seen in terms of PGIC, CGIC, and Health-related QOL in patients treated with melatonin than placebo. Melatonin was also well tolerated.. The present results showed that melatonin as an adjunct therapy to pregabalin might be helpful for use in patients with PDN. However, confirmation of these results requires further studies.

Topics: Aged; Analgesics; Central Nervous System Depressants; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Therapy, Combination; Humans; Male; Melatonin; Middle Aged; Pain Measurement; Pregabalin; Quality of Life; Sleep Quality

To evaluate the clinical effect of perineural platelet-rich plasma (PRP) injection for pain and numbness alleviation in diabetic peripheral neuropathy (DPN).. A randomized prospective clinical trial.. Pain clinic and Rheumatology and Rehabilitation Departments, Assiut University Hospital.. Sixty adult patients with type II DM accompanied by DPN of at least six months' duration were assessed by modified Toronto Clinical Neuropathy Score (mTCNS) and randomly allocated into two groups. Group I underwent ultrasound-guided perineural PRP injection and medical treatment, and Group II received medical treatment only. Patients were followed up at months 1, 3, and 6 with regard to pain and numbness visual analog scale (VAS) and mTCNS scores.. Significant improvement was recorded in pain and numbness VAS scale scores in group I vs group II (P ≤ 0.001 during the whole study period for both parameters); at the same time, mTCNS improved in group I in comparison with group II with P = 0.01, 0.001, and <0.001 at months 1, 3, and 6, respectively.. Perineural PRP injection is an effective therapy for alleviation of diabetic neuropathy pain and numbness and enhancement of peripheral nerve function.

Topics: Adult; Analgesics; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Glycemic Control; Humans; Hypesthesia; Injections; Male; Median Nerve; Middle Aged; Neural Conduction; Neuralgia; Pain Measurement; Peroneal Nerve; Platelet-Rich Plasma; Pregabalin; Radial Nerve; Selective Serotonin Reuptake Inhibitors; Sural Nerve; Thioctic Acid; Tibial Nerve; Treatment Outcome; Ulnar Nerve; Vitamin B Complex

Limited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN).. An 11-week double-blind placebo-controlled trial was performed in Chinese pDPN patients randomized (1 : 1) to 300 mg/day pregabalin or placebo. The primary outcome was change from baseline to endpoint in mean pain score (MPS; 0, no pain; 10, worst possible pain; using the mean of the last seven daily pain scores). Secondary outcomes included weekly MPS and responder status (MPS reduced by ≥30% or ≥50% vs baseline). Subgroup analysis assessed patients with severe (≥7) baseline MPS. Adverse events (AEs) were reported.. In all, 620 patients were randomized (pregabalin, n = 313; placebo, n = 307). Improvement in MPS with pregabalin versus placebo was not significant (P = 0.0559). Post hoc sensitivity analyses, excluding one patient/site due to Good Clinical Practice (GCP) non-compliance, showed pregabalin significantly improved MPS when excluding the patient (P = 0.0448) or site (P = 0.0142). Pregabalin significantly improved weekly MPS (P = 0.0164) and ≥50% responders at endpoint (P = 0.0384). Improvement in proportion of ≥30% responders, impression of change, pain intensity, and sleep did not differ significantly between the treatment groups. In the severe pDPN subpopulation, pregabalin significantly improved MPS versus placebo (P = 0.0040). The most commonly reported AE was dizziness (9.6% vs 3.9% with placebo).. Pregabalin did not significantly improve the primary measure of pain in the trial. Significant reductions in MPS were observed when excluding the GCP non-compliant patient/site and in the severe pDPN subpopulation. Pregabalin was well tolerated in Chinese pDPN patients.

Topics: Adolescent; Adult; Aged; Asian People; Biomarkers; Calcium Channel Blockers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pain Measurement; Pregabalin; Safety; Treatment Outcome; Young Adult

Subjects with diabetes mellitus (DM) develop gait dysfunction contributing to falls, reluctance to perform activities and injuries. Neuropathic pain (NeP) related to diabetic peripheral neuropathy (DPN) is associated with increased gait variability that may contribute to gait dysfunction. We used a portable device (GaitMeter™) and related gait and balance measures to measure gait parameters in painful DPN (PDPN) subjects prior to and during analgesia. Our hypothesis was that PDPN subjects would have decreased gait step variability when receiving pharmacological relief of NeP.. DPN subjects with at least moderate NeP were assessed in a randomized, double-blind crossover study of pregabalin versus placebo. The outcome measure was variability in step length and step velocity. Testing for Timed Get-Up-and-Go Test, Tinetti Mobility Scales, Sway Testing, a Physiological Profile Approach, and fall-related surveys were also performed. DPN severity was quantified using the Utah Early Neuropathy Score.. PDPN subjects developed increased, rather than decreased, step length and step velocity variability during pregabalin treatment. There were no significant differences between cohorts for other physiological gait and balance testing. Non-significant NeP relief occurred in the pregabalin phase of study as compared with placebo. There was a negative relationship for step length with pain severity.. Analgesia did not decrease gait variability in PDPN patients, and in fact, increased gait variability was seen during pregabalin treatment. Other important relationships of gait dysfunction with PDPN should be sought.

Topics: Aged; Analgesics; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Gait; Gait Disorders, Neurologic; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Pregabalin

We aimed to identify doses of mirogabalin (DS-5565) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain (DPNP).. Adults (≥18 years) with type 1 or 2 diabetes, HbA₁c ≤10% at screening, and DPNP for ≥6 months were eligible for study participation. Subjects (n = 452) were randomized (2:1:1:1:1:1:1 ratio) to placebo, dose-ranging mirogabalin (5, 10, 15, 20, and 30 mg/day), or pregabalin (300 mg/day) for 5 weeks. The primary end point was weekly change in average daily pain score (ADPS; 0 to 10 numeric rating scale) from baseline to week 5 (minimally meaningful effect, ≥1.0-point decrease versus placebo). ANCOVA was conducted using last observation carried forward, and treatment effect least squares (LS) means were provided for each contrast. Safety assessments included adverse events (AEs), clinical laboratory tests, and electrocardiograms.. LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22, -0.53, -0.94, -0.88, and -1.01 for the mirogabalin 5-, 10-, 15-, 20-, and 30-mg/day treatment groups, respectively, and -0.05 in the pregabalin group (P < 0.05 versus placebo for mirogabalin 15, 20, and 30 mg/day). Most frequent AEs (n = 277) were primarily mild to moderate dizziness (9.4%), somnolence (6.1%), and headache (6.1%); otherwise, mirogabalin was well tolerated.. Mirogabalin 15, 20, and 30 mg/day had statistically significant reductions in ADPS versus placebo, and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect. Mirogabalin may be a promising new treatment option for patients with DPNP.

Topics: Adult; Aged; Analgesics; Bridged Bicyclo Compounds; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Placebos; Pregabalin; Treatment Outcome

To evaluate the efficacy, safety and pharmacokinetics of pregabalin in treating neuropathic pain associated with diabetic peripheral neuropathy in Japanese patients.. A randomized, double-blind, placebo-controlled, multicentre 14 week clinical trial was conducted. Japanese patients with diabetic peripheral neuropathy (n = 317) were randomized to receive placebo or pregabalin at 300 or 600 mg/day. The primary efficacy measure was a change of mean pain score from baseline to end-point from patients' daily pain diaries.. Significant reductions in pain were observed in patients treated with pregabalin at 300 and 600 mg/day vs. placebo (P < 0.05). Improvements in weekly pain scores were observed as early as week 1 and were sustained throughout the study period (300 and 600 mg/day difference from placebo at study end-point, -0.63 and -0.74, respectively). Pregabalin produced significant improvements in weekly sleep interference scores, the short-form McGill Pain Questionnaire, the Medical Outcomes Study-Sleep Scale, the 36-item Short-Form Health Survey scale, and the Patient and Clinical Global Impression of Change. Patient impressions of numbness, pain and paraesthesia were also significantly improved. Regarding treatment responders, 29.1 and 35.6% of patients treated with 300 and 600 mg/day, respectively, reported ≥ 50% improvement in mean pain scores (vs. 21.5% for placebo). Pregabalin was well tolerated; somnolence (26%), dizziness (24%), peripheral oedema (13%) and weight gain (11%) were the most common adverse events and generally were reported as mild to moderate.. Pregabalin was effective in reducing pain and improving sleep disturbances due to pain, and was well tolerated in Japanese patients with painful DPN.

Topics: Analgesics; Asian People; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Administration Schedule; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain Measurement; Placebos; Pregabalin; Surveys and Questionnaires; Treatment Outcome

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

We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics.

Topics: Animals; Calcium Channels; Caproates; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Models, Animal; Ligands; Mice; Molecular Structure; Neuralgia; Sulfhydryl Compounds

The objective of this study was to compare the efficacy and safety of pregabalin for painful diabetic peripheral neuropathy (pDPN) in subjects with type 1 (T1DM) or 2 diabetes mellitus (T2DM).. Pooled data from 10 randomized clinical trials (pregabalin-treated T1DM and T2DM subjects with pDPN) were analyzed for change from baseline (CFB) scores (pain and sleep disturbance) using mixed model repeated measures (MMRM) through Week 12 and last observation carried forward (LOCF). Adverse events (AEs) were recorded.. Pregabalin-treated (T1DM 156 [8.7%]; T2DM 1632 [91.3%]) and placebo subjects (T1DM 92 [9.6%]; T2DM 868 [90.4%]) had comparable baseline demographic characteristics between treatment groups within the same diabetes type. T2DM (vs. T1DM) subjects were ∼10 years older. With pregabalin and placebo, respectively, mean ± SD baseline pain (T1DM: 6.2 ± 1.4 and 6.5 ± 1.6; T2DM: 6.5 ± 1.5 and 6.4 ± 1.5) and sleep scores (T1DM: 5.2 ± 2.4 and 5.2 ± 2.7; T2DM: 5.3 ± 2.5 and 5.1 ± 2.5) were comparable. Using MMRM, mean CFB treatment differences (pregabalin minus placebo) were significantly different for pain and sleep with either diabetes types (all weeks p < .05). With LOCF, pregabalin's odds ratios (ORs) of achieving 30% pain reduction were similar with T2DM (OR, 1.91, 95% CI [1.61, 2.27]) and T1DM (2.01 [1.18, 3.44]) (both p ≤ .01). Pregabalin's ORs of 30% improvement in sleep quality were 1.81 (95% CI, 1.06, 3.09) with T1DM and 2.01 (1.69, 2.39) with T2DM (both p < .05). AEs were consistent with the known safety profile of pregabalin.. Pregabalin significantly improved pain and sleep quality, without a clinically meaningful difference between diabetes types. ClinicalTrial.gov registration: NCT00156078, NCT00159679, NCT00143156, NCT00553475.

Topics: Analgesics; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Monitoring; Dyssomnias; Female; Humans; Male; Middle Aged; Pain Measurement; Pregabalin; Randomized Controlled Trials as Topic; Treatment Outcome

To assess metabolic parameters in patients with diabetic peripheral neuropathy (DPN) before and after 3 months treatment with a flexible dose pregabalin.. This is a prospective clinical trial. The metabolic parameters observed and recorded after 3 months treatment with a flexible dose pregabalin (n=331).. The lipid profile parameters were significantly improved after treatment, total cholesterol, TC (P<0.01, 95% CI, 25.91-41.98), low-density lipoprotein, LDL (P<0.01, 95% CI, 21.11-34.80), triglycerides, TG (P<0.001, 95% CI, 56.43-79.26), all the three parameters significantly decreased while high-density lipoprotein, HDL, significantly increased (P<0.05, 95% CI, -8.61 to -5.51). Microalbumin mean was 16±1.39 before treatment versus 6.5±0.59 after treatment. Glycolated hemoglobin, HbA1c mean was 9.6±0.099 before pregabalin therapy and 7.6 ±0.06 after. BMI mean was 33.5±0.45 before versus 31.1±0.33 after (P<0.001). HbA1C was positively correlated with DPN severity before treatment (r=0.18, P<0.01). Same results were observed with weight and waist circumference (r=0.17, P<0.01, r=0.14, P<0.05 respectively). Oral anti diabetic medications (OAD) were also positively correlated to DPN severity before treatment (r=0.115, P<0.05).. Prompt treatment of DPN has a significant effect on the metabolic parameters.

Topics: Blood Glucose; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Pregabalin; Prognosis; Prospective Studies; Waist Circumference

Patients with diabetes often develop peripheral nerve complications, including numbness and pain in the extremities. Diabetes-induced peripheral neuropathic pain is characterized by hypersensitivity to innocuous stimuli, known as tactile allodynia. Pregabalin (PGN) is currently used to treat diabetes-induced peripheral neuropathy and alleviates allodynia. In the present study, we demonstrated that the antiallodynic effect of PGN on diabetic mice was modulated by circadian changes in its intestinal absorption. A single intraperitoneal administration of 200 mg/kg streptozotocin (STZ) to mice induced type I diabetic pathologic changes that were accompanied by tactile allodynia. The intensity of tactile allodynia in STZ-induced diabetic mice was alleviated by the oral administration of PGN; however, the antiallodynic effect varied according to its dosing time. The analgesic effect of PGN was enhanced by its administration at the times of day when its intestinal absorption was accelerated. Organic cation transporter novel type 1 (Octn1) mediated the uptake of PGN into intestinal epithelial cells. The expression of Octn1 in the small intestine of STZ-induced diabetic mice oscillated in a circadian time-dependent manner. This oscillation in Octn1 appeared to cause the time of day-dependent changes in the intestinal absorption of PGN. Similar dosing time dependencies of the antiallodynic effect of PGN and oscillation in Octn1 expression were also detected in type II diabetic db/db mice. These results suggested that the dosing time-dependent differences in the analgesic effect of PGN were attributable to circadian oscillations in the intestinal expression of Octn1 and also that optimizing its dosing schedule may assist in achieving rational pharmacotherapy for diabetes-induced peripheral neuropathic pain.

Topics: Analgesics; Animals; Calcium Channels; Carrier Proteins; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Epithelial Cells; gamma-Aminobutyric Acid; Humans; Hyperalgesia; Intestinal Absorption; Jejunum; Membrane Proteins; Mice, Inbred ICR; Organic Cation Transport Proteins; Pregabalin; Spinal Cord; Symporters; Time Factors; Touch

Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Duloxetine Hydrochloride; Evidence-Based Medicine; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Thiophenes; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Density Conservation Agents; Boronic Acids; Bortezomib; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diagnosis, Differential; Diphosphonates; gamma-Aminobutyric Acid; Humans; Imidazoles; Male; Melphalan; Multiple Myeloma; Nerve Compression Syndromes; Neuralgia; Phrenic Nerve; Prednisone; Pregabalin; Protease Inhibitors; Pyrazines; Respiratory Paralysis; Zoledronic Acid

Topics: Amyloid; Analgesics; Anticonvulsants; Antiparkinson Agents; Diabetes Mellitus, Type 2; Diphtheria-Tetanus-Pertussis Vaccine; Drug Approval; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Exenatide; gamma-Aminobutyric Acid; Heart Failure; Humans; Hydralazine; Hypoglycemic Agents; Indenes; Indoles; Islet Amyloid Polypeptide; Isosorbide Dinitrate; Patient Education as Topic; Patient Selection; Peptides; Pregabalin; Sleep Wake Disorders; United States; United States Food and Drug Administration; Venoms