title: Determination of the effective dose of pregabalin on human experimental pain using the sequential up-down method.
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 (cm(2)). 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Cedars Sinai Medical Center, Los Angeles, California.
authors.forename: Waylan
authors.initials: W
authors.lastname: Wong
authors.affiliation: Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, La Jolla, California. Electronic address: mswallace@ucsd.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wallace
mesh_terms: D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D002211:Capsaicin / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D002211:Capsaicin
keywords: Pregabalin; experimental; median effective dose; pain; up-down method