Bradshaw H, Miller J, Ling Q, Malsnee K, Ruda M A
Neuroscience Program, Florida State University, Tallahassee, USA.
Pain. 2000 Mar;85(1-2):93-9. doi: 10.1016/s0304-3959(99)00253-5.
The neuromodulatory interactions of sex steroids with the opioid system may result in sex differences in pain and analgesia. Dynorphin is an endogenous kappa-opioid peptide that is upregulated in an animal model of peripheral inflammation and hyperalgesia and is possibly regulated by circulating levels of sex steroids. The present study compared behavioral responses of male, cycling female, and gonadectomized Sprague-Dawley rats in a model of persistent pain. Cycling female rats were behaviorally tested over a 14-day period, and their estrous cycles were monitored by daily vaginal smears. Thermal hyperalgesia was measured by paw withdrawal latencies taken prior to and 24-72 h after rats received a unilateral hindpaw injection of complete Freund's adjuvant (CFA). Prior to CFA administration, there was no significant difference in paw withdrawal latencies between male rats, cycling female rats, and ovariectomized female rats. Following CFA administration, female rats in proestrus exhibited significantly increased hyperalgesia compared with male rats, ovariectomized female rats, and female rats in other estrous stages (P</=0.05). Levels of spinal preprodynorphin (PPD) mRNA induction in the L4-L5 segments were assessed by Northern blot analysis. PPD mRNA expression ipsilateral to the injected paw was significantly higher in female rats in diestrus (P</=0.05) and proestrus (P</=0.01) compared with rats in estrus and intact male rats. Ovariectomized rats had significantly higher levels of PPD mRNA expression compared with intact male rats (P</=0.05). However, castrated male rats had significantly lower levels of PPD mRNA expression than intact male rats (P</=0.05). PPD mRNA expression was not altered on the contralateral side of the spinal cord in any group. These results suggest a hormonal regulatory influence on the response of spinal cord dynorphin neurons to chronic inflammation and furthermore, that the association of the endocrine and opioid systems have the ability to influence an animal's sensitivity to pain.
性类固醇与阿片系统的神经调节相互作用可能导致疼痛和镇痛方面的性别差异。强啡肽是一种内源性κ-阿片肽，在周围炎症和痛觉过敏的动物模型中上调，并且可能受性类固醇循环水平的调节。本研究比较了雄性、处于发情周期的雌性以及去势的Sprague-Dawley大鼠在持续性疼痛模型中的行为反应。对处于发情周期的雌性大鼠进行了为期14天的行为测试，并通过每日阴道涂片监测其发情周期。通过在大鼠单侧后爪注射完全弗氏佐剂（CFA）之前及之后24 - 72小时测量爪退缩潜伏期来测定热痛觉过敏。在给予CFA之前，雄性大鼠、处于发情周期的雌性大鼠和去卵巢雌性大鼠之间的爪退缩潜伏期没有显著差异。给予CFA后，处于发情前期的雌性大鼠与雄性大鼠、去卵巢雌性大鼠以及处于其他发情阶段的雌性大鼠相比，痛觉过敏显著增加（P≤0.05）。通过Northern印迹分析评估L4 - L5节段脊髓前强啡肽原（PPD）mRNA的诱导水平。与发情期大鼠和完整雄性大鼠相比，处于动情后期（P≤0.05）和发情前期（P≤0.01）的雌性大鼠注射侧爪同侧的PPD mRNA表达显著更高。去卵巢大鼠的PPD mRNA表达水平显著高于完整雄性大鼠（P≤0.05）。然而，去势雄性大鼠的PPD mRNA表达水平显著低于完整雄性大鼠（P≤0.05）。任何组脊髓对侧的PPD mRNA表达均未改变。这些结果表明激素对脊髓强啡肽神经元对慢性炎症的反应有调节作用，此外，内分泌系统和阿片系统的关联有能力影响动物对疼痛的敏感性。
