Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation.
Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.
Department of Anesthesiology, National Defense Medical Center, Taipei, Nei-Hu, Taiwan, ROC.|Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Department of Anesthesiology, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
Lok-Hi
LH
Chow
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Nei-Hu, Taiwan, ROC.
Yuan-Hao
YH
Chen
Department of Pharmacology, National Defense Medical Center, Nei-Hu, Taipei, Taiwan, ROC.
Wan-Chuan
WC
Wu
Department of Pharmacology, National Defense Medical Center, Nei-Hu, Taipei, Taiwan, ROC.
En-Pei
EP
Chang
Department of Pharmacology, National Defense Medical Center, Nei-Hu, Taipei, Taiwan, ROC.
Eagle Yi-Kung
EY
Huang
D000818:Animals; D015153:Blotting, Western; D002351:Carrageenan; D010122:Cystinyl Aminopeptidase; D004487:Edema / Q000150:complications / Q000473:pathology; D005260:Female; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced* / Q000150:complications / Q000473:pathology*; D007278:Injections, Spinal; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008297:Male; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*
D010121:Oxytocin; D002351:Carrageenan; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase