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Effect of Chronic Oral Gabapentin on Capsaicin-induced Pain and Hyperalgesia: A Double-blind, Placebo-controlled, Crossover Study

Wallace, Mark S. MD; Schulteis, Gery PhD

doi: 10.1097/AJP.0b013e3181673b93
Original Articles

Objectives There is an abundance of literature on the efficacy of gabapentin for the treatment of neuropathic pain. Two studies have demonstrated an effect of a single dose of gabapentin on experimental cutaneous hyperalgesia. This study evaluated the effect of chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia.

Methods A randomized, double-blinded, placebo-controlled crossover design methodology was conducted. Participants took part in two 10-day study sessions, separated by a 7-day washout period. One session was with gabapentin and one with placebo. Study drug was administered 300 mg b.i.d. from day 1 to 3, 300 mg q.i.d. from day 4 to 6 and 600 mg t.i.d. from day 7 to 10. At baseline, day 4, day 7, and day 10, quantitative sensory testing was performed to thermal and mechanical stimuli. On day 10, only intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Side effects were recorded by the participants each evening.

Results Thirteen participants were enrolled into the study. Three dropped out because of intolerable side effects. Ten participants completed the study and were able to tolerate the highest dose of gabapentin. Oral gabapentin had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. There were significantly more side effects associated with gabapentin with sedation and dizziness being the most common.

Discussion This study demonstrated a lack of effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. The discrepancy of this finding with other studies using single oral doses may be the result of differences in the models used and differences in drug kinetics and plasma levels. The results of this study do not correlate with the clinical studies on gabapentin, which demonstrate efficacy at 1800 mg/d.

Department of Anesthesiology, University of California, San Diego, CA

Supported by NIH K08 NS01909-01A2 and the Pharmaceutical Research and Manufacturers of America Grant.

Reprints: Mark S. Wallace, MD, Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive No. 0924, La Jolla, CA 92093-0924 (e-mail:

Received for publication October 15, 2007; revised December 27, 2007; accepted January 3, 2008

© 2008 Lippincott Williams & Wilkins, Inc.