Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation

Abstract

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.

Neonatal complete Freund's adjuvant-induced inflammation does not induce or alter hyperalgesic priming or alter adult distributions of C-fibre dorsal horn innervation

“…In this study, carrageenan-induced decreases in mechanical withdrawal thresholds were slower to resolve in females than in males. This correlates with other reports of increased severity or duration of mechanical or heat hypersensitivity after intraplantar carrageenan in female rodents, 13 , 35 although this effect was not shown by Joseph et al 26 who found that duration and severity was increased in male compared to female rats. Females have been shown to produce a larger proinflammatory immune response to tissue damage than males, potentially resulting in the accumulation of increased levels of proinflammatory cytokines that result in peripheral sensitization.…”

Plasticity and Function of Spinal Oxytocin and Vasopressin Signaling during Recovery from Surgery with Nerve Injury

“…Similarly, there is not a sex difference in the anti-mechanical hypersensitivity effect of intrathecal oxytocin itself in rats, although its duration of action is shorter in females. 28 Our anatomic and behavioral data do not support a major sex difference in tonic spinal oxytocin signaling during recovery from surgery and confirm our previous findings 5 of a lack of sex difference in speed of recovery after surgery. Ongoing clinical trials of intrathecal oxytocin 29 will determine whether there is a sex difference in humans.…”

Antioxidant Capacity of Chuquiraga Spinosa Less. "Huamanpinta" and Prevention of Carrageenan-Induced Inflammation in Mice

“…After 3 hours, the groups treated with ChS70, dexamethasone and carrageenan control were given 1 mL of 2% carrageenan in the air bag and the white group was given 1 mL of saline solution. Twenty-four hours later, mice were euthanized as described by Chow et al and Huang 26,27 with pentobarbital at a dose of 100 mg/kg intraperitoneally, then the air sac was incised, the exudate was collected in ice-cold test tubes, centrifuged at 3000 x g, the supernatant was used for determination of biochemical parameters and the precipitate for determination of leukocyte number and differentiation. A segment of the air sac tissue was fixed in buffered formalin for histological evaluation.…”