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Determination of the Effective Dose of Pregabalin on Human Experimental Pain Using the Sequential Up-Down Method

  • Waylan Wong
    Affiliations
    Department of Anesthesiology, Cedars Sinai Medical Center, Los Angeles, California
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  • Mark S. Wallace
    Correspondence
    Address reprint requests to Mark S. Wallace, MD, University of California, Department of Anesthesiology, UCSD Thornton Hospital, 9300 Campus Point Dr, #7651, La Jolla, CA 92037.
    Affiliations
    Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, La Jolla, California
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Published:November 21, 2013DOI:https://doi.org/10.1016/j.jpain.2013.08.011

      Abstract

      The intradermal capsaicin pain model has been used to evaluate analgesic effects of a variety of drugs. Using the sequential up-down method, we examined the analgesic effects of pregabalin on intradermal capsaicin pain. Using a double-blind, placebo-controlled, crossover study, healthy adult men were randomized to oral pregabalin or placebo on the first visit and returned for the opposite treatment after a washout period. Dosing was set by the Dixon sequential up-down method; that is, a greater or less than 30% reduction in capsaicin pain decreased or increased the dose, respectively, by a fixed interval for the next subject. The median effective dose (ED50) was derived once 7 changes in dose direction occurred. Secondary outcome measures included secondary hyperalgesia and tactile and thermal allodynia, and their respective areas (cm2). Thirteen subjects were required to derive the pregabalin ED50: 252 mg (95% confidence interval 194, 310 mg). Most common side effects were drowsiness (46%), euphoria (31%), and dizziness (7%). Those with ≥30% pain reduction as compared to placebo also had similar reductions in secondary outcome measures. The intradermal capsaicin pain model can be used to efficiently derive the pregabalin ED50, but well-powered dose-response curve studies are needed for comparison and validation.

      Perspective

      Using the Dixon sequential up-down method, the ED50 of pregabalin on intradermal capsaicin induced pain was successfully calculated (252 mg) using only 13 subjects.

      Key words

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