17Beta-estradiol mediates the sex difference in capsaicin-induced nociception in rats.
We have previously shown that the male sex steroid testosterone inhibits slightly, but the female sex steroid 17beta-estradiol (E(2)) potentiates dramatically, the capsaicin receptor-mediated current in rat dorsal root ganglion (DRG) neurons. Here, we used pharmacological methods and the nociceptive behavioral test to determine whether there is a sex difference in capsaicin-induced acute pain in rats in vivo and what mechanism underlies this sex difference. Results revealed that intradermal injection of capsaicin induced a dose-dependent nocifensive response in males and females, with the dose required to produce a comparable level of nociception being approximately 3- to 4-fold higher in males than in females. In addition, females during the proestrus stage exhibited significantly greater capsaicin-induced nocifensive responses compared with the estrus stage. Moreover, the female's enhanced sensitivity to the capsaicin-induced nocifensive response was completely reversed by ovariectomy 6 weeks before capsaicin injection. It is noteworthy that intradermal coinjection of E(2) but not progesterone with capsaicin potentiated the capsaicin-induced nocifensive response in ovariectomized rats. Likewise, intradermal E(2) injection dose-dependently potentiated the capsaicin-induced nocifensive response in male rats. Furthermore, potentiation by E(2) of the capsaicin-induced nocifensive response in male rats was not significantly reduced by a selective protein kinase C (PKC) inhibitor or by a selective protein kinase A (PKA) inhibitor, indicating that neither PKC nor PKA was involved in the effect of E(2). These data demonstrate that E(2) mediates the female's enhanced sensitivity to capsaicin-induced acute pain, consistent with potentiation by E(2) of the capsaicin receptor-mediated current in rat DRG neurons.
Department of Physiology, College of Medicine, National Cheng Kung University, 1, Ta-Hsiue Road, Tainan 70101, Taiwan.
Yu-Ching
YC
Lu
Chao-Wei
CW
Chen
Su-Yi
SY
Wang
Fong-Sen
FS
Wu
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D007271:Injections, Intradermal; D008297:Male; D010052:Ovariectomy; D010146:Pain / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology*; D012727:Sex Characteristics
D047428:Protein Kinase Inhibitors; D018689:Sensory System Agents; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002211:Capsaicin