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This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.054478v1 307/1/237    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barrett, A. C. Articles by Picker, M. J. Search for Related Content PubMed PubMed Citation Articles by Barrett, A. C. Articles by Picker, M. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CAPSAICIN MORPHINE

BEHAVIORAL PHARMACOLOGY

Capsaicin-Induced Hyperalgesia and µ-Opioid-Induced Antihyperalgesia in Male and Female Fischer 344 Rats

Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

The influence of sex in determining responses to opioid analgesics has been well established in rodents and monkeys in assays of short-lasting, phasic pain. The purpose of this investigation was to use a capsaicin model of tonic pain to evaluate sex differences in hyperalgesia and µ-opioid-induced antihyperalgesia in Fischer 344 (F344) rats. Capsaicin injected into the tail produced a dose-dependent thermal hyperalgesia in males and females, with the dose required to produce a comparable level of hyperalgesia being 3.0-fold higher in males than in females. These sex differences were modulated by gonadal hormones, inasmuch as gonadectomy increased the potency of capsaicin in males and decreased its potency in females. Morphine, buprenorphine, and dezocine administered by various routes [systemic (s.c.), local (in the tail), and central (i.c.v.)] generally produced marked antihyperalgesic effects in males and females. Although in most instances these opioids were equally potent and effective in males and females, selected doses of local and i.c.v. administered buprenorphine produced greater effects in females. When administered locally, the antihyperalgesic effects of morphine were mediated by peripheral opioid receptors in both males and females, since this effect was not reversed by i.c.v. naloxone methiodide. These data contrast with the finding that µ-opioids are more potent in male rodents in assays of phasic pain, thus suggesting that distinct mechanisms underlie male and female sensitivity to opioid antinociception in phasic and tonic pain models. These findings emphasize the need to test male and female rodents in tonic pain assays that may have greater relevance for human pain conditions.

Address correspondence to: Andrew C. Barrett, Department of Psychology, Davie Hall, CB #3270, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail address: barrett3{at}email.unc.edu

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