National Institutes of Health -- Gender and Pain: Scientific Abstracts

THE ROLE OF SEX STEROIDS IN GENDER DIFFERENCES IN PROSTAGLANDIN E₂- INDUCED PERIPHERAL HYPERALGESIA

William M. Isenberg, M.D., Ph.D., Department of Oral & Maxillofacial Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California

Sex differences in nociception and antinociception have largely focused on the central nervous system. To study sex differences in peripheral nociceptive mechanisms we examined the role of sex steroids in the response of rats to an intradermal injection of the direct-acting hyperalgesic inflammatory mediator prostaglandin E₂ (PGE₂). Baseline mechanical nociceptive threshold was similar in adult male and female rats and was not influenced by administration of the opposite sex’s major sex steroid. However, female rats had significantly greater hyperalgesia in response to PGE₂. Females receiving testosterone, as chronic implants following gonadectomy, acute intramuscular injection, or acute intradermal injection at the site of nociceptive testing in normal rats, had PGE₂-induced hyperalgesia similar to that of control males. Conversely, males receiving 17b-estradiol by the same routes, had nociceptive thresholds like those of control females. Rat dorsal root ganglion (DRG) neurons have been shown to contain estrogen receptor-a in small- and medium-diameter neurons. In this study we found that small- and medium-diameter neurons within DRGs also contain androgen receptor-like immunoreactivity. These studies suggest that there are basic biologic differences between males and females at the level of the primary afferent nociceptor and in particular in the hyperalgesic effect of the direct-acting hyperalgesic inflammatory mediator PGE₂. Sex steroid hormones account for most of these differences.