Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

Abstract

Context.-Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies.Objective.-To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy.Design.-Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. Setting.-Outpatient clinics at 20 sites. Patients.-The 165 patients enrolled had a 1-to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form Mc-Gill Pain Questionnaire visual analogue scale. Intervention.-Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. Main Outcome Measures.-The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results.Results.-Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (PϽ.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; PϽ.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06).Conclusion.-Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.

Suppression of Formalin-Induced Nociception by Cilnidipine, a Voltage-Dependent Calcium Channel Blocker

“…In the present study, furthermore, gabapentin, a clinically available drug for treatment of neuropathic pain, 42,43) suppressed formalin-induced nociception in phase 2 with minimal effects on phase 1, in agreement with a previous finding. 44) A comparison of cilnidipine-and gabapentin-produced antinociception in phase 2 (the persistent nociceptive phase 45) ) of the formalin model showed that cilnidipine had a greater potency on phase 2 nociception.…”

Gabapentin for the Symptomatic Treatment of Chronic Neuropathic Pain in Patients with Late-Stage Lyme Borreliosis: A Pilot Study

“…Gabapentin was initially introduced as an anti-epileptic drug for the treatment of partial seizures with or without secondary generalization [7,9,10,11,12]. Besides epilepsy, it is used for the treatment of migraine, bipolar illness or movement disorders, namely restless legs syndrome, essential tremor or nystagmus [13, 14].…”

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

“…In humans, gabapentin does not increase thermal and mechanical pain thresholds (51) or tolerance to cold pressure test (17), but it reduces stroking and punctate hyperalgesia in experimental central sensitization (18,52). Gabapentin also reduced pain intensity in patients with postherpetic neuralgia and diabetic neuropathy, as shown in two large, placebocontrolled studies (14,15), although it must be noted that the modality of gabapentin administration in patients (by slowly increasing the dose over weeks) is considerably different from the single-dose administration we adopted in this study (because of the time constraints of the fMRI experimental design). The fact that our results have been obtained in a time window of 1-2 h after hyperalgesia induction confirms the concept that gabapentin is also effective in counteracting acute hyperalgesia, and that the upregulation of the ␣2␦ subunit of the voltage-dependent calcium channel, occurring in animal models of hyperalgesia with a time course of several days (53), is not a prerequisite for its action.…”

“…It has an analgesic effect documented in several rat models of neuropathic pain (12, 13) and in patients with different neuropathic pain conditions, such as postherpetic neuralgia and painful diabetic neuropathy (14,15). Experimental studies in animals and human volunteers have shown that, although gabapentin exerts a minimal modulation of normal synaptic transmission in the dorsal horn (i.e., it has a negligible antinociceptive effect) (16, 17), it is clearly able to modulate the development of and synaptic transmission during central sensitization (i.e., it has a stronger antihyperalgesic effect) (16, 18).…”