Estradiol and progesterone differentially regulate formalin-induced nociception in ovariectomized female rats.
Clinical and preclinical studies have found sex-specific differences in the discrimination and perception of inflammatory stimuli. The emerging picture suggests that the biological basis of these differences resides in the regulatory activity of gonadal hormones in the central nervous system. This study describes the effects of ovarian hormones in inflammatory pain processes. Ovariectomized rats received estradiol and/or progesterone, and the number of paw flinches was measured after 1, 2.5 or 5% formalin administration. Both estradiol and progesterone altered the number of flinches only after 1% formalin administration. Estradiol significantly reduced the overall number of flinches during Phase II of the formalin nociceptive response while progesterone attenuated Phase I of the response. After co-administration of estradiol and progesterone, progesterone reversed estradiol's analgesic effect in Phase II, however, estradiol did not reverse progesterone's analgesic activity in Phase I. To determine if estradiol effects are receptor-mediated, tamoxifen (selective estrogen receptor mediator, 15 mg/kg) or alpha-estradiol (an inactive isomer of estradiol, 20 microg) were utilized. Tamoxifen decreased the number of formalin-induced flinches during Phase II while alpha-estradiol did not affect any formalin-induced responses. When co-administered with estradiol, tamoxifen failed to reverse estradiol's effect, suggesting both tamoxifen and estradiol activate similar intracellular mechanisms. Although Western blot analysis detected the presence of estradiol alpha and beta and progesterone B receptors in the spinal cord, hormone replacement treatments had no effects on the levels of these receptors. We postulate that the mechanisms by which estradiol and progesterone induce analgesia occur through the activation of their receptor at the spinal cord level.
Kuba
Tzipora
T
Department of Psychology, Hunter College and The Graduate Center of the City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Wu
Hui-Bing K
HB
Nazarian
Arbi
A
Festa
Eugene D
ED
Barr
Gordon A
GA
Jenab
Shirzad
S
Inturrisi
Charles E
CE
Quinones-Jenab
Vanya
V
D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D004958:Estradiol / Q000819:agonists / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D010052:Ovariectomy; D010146:Pain / Q000097:blood / Q000139:chemically induced; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D013629:Tamoxifen; D005557:Formaldehyde; D011374:Progesterone; D004958:Estradiol