Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats.
We have previously shown that the neurosteroid pregnenolone sulfate (PS) inhibits the capsaicin receptor-mediated current in rat dorsal root ganglion neurons. Here, we examined the effect of intradermal injection of PS into the rat hindpaw on capsaicin-induced nociception. Results revealed that PS co-injected with capsaicin dose-dependently inhibited the capsaicin-induced nocifensive response. In contrast, injections of PS into one hindpaw and capsaicin into the contralateral hindpaw had no effect on the capsaicin-induced nocifensive response, suggesting that PS produced its effect locally but not systemically. Moreover, PS inhibition of the capsaicin-induced nocifensive response was not significantly reduced by a nonselective opioid receptor antagonist or by cannabinoid receptor antagonists, indicating that neither an opioid- nor a cannabinoid-dependent mechanism mediated the effect of PS. These data demonstrate that PS acts peripherally to attenuate capsaicin-induced nociception through an opioid- and cannabinoid-independent mechanism and suggest a new therapeutic potential for PS in pain management.
Chen
Shu-Cheng
SC
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Liu
Bie-Ching
BC
Chen
Chao-Wei
CW
Wu
Fong-Sen
FS
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000378:metabolism; D007271:Injections, Intradermal; D008297:Male; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D011284:Pregnenolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002186:Cannabinoids; C018370:pregnenolone sulfate; D011284:Pregnenolone; D002211:Capsaicin