新生儿处理导致雄性大鼠对应激诱导性肌肉痛觉过敏产生依赖性激素的弹性。
Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.
机构信息
Department of Oral and Maxillofacial Surgery, University of California, San Francisco, California; Division of Neuroscience, University of California, San Francisco, California.
Division of Neuroscience, University of California, San Francisco, California; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, California.
出版信息
J Pain. 2018 Jun;19(6):670-677. doi: 10.1016/j.jpain.2018.01.009. Epub 2018 Feb 9.
UNLABELLED
Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia.
PERSPECTIVE
NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress.
未加标签
雄性幼鼠的新生期处理（NH）强烈减弱了成年后应激反应和应激诱导的持续性肌肉痛觉过敏。由于女性性别是应激诱导慢性肌肉疼痛的一个既定危险因素，我们探讨了 NH 是否为成年雌性大鼠的应激诱导性痛觉过敏提供了弹性。幼鼠接受 NH 或标准（对照）护理。当它们成年后，评估肌肉机械性伤害感受阈值在水回避（WA）应激前后的变化。与雄性大鼠不同，NH 仅对雌性大鼠的 WA 应激诱导性肌肉痛觉过敏产生适度的保护作用。去势完全消除了 NH 诱导的雄性大鼠的弹性，但在雌性大鼠中仅略微增加了这种保护作用。除了去势之外，抗雌激素药物氟维司群的给药并没有增强 NH 在雌性大鼠中的保护作用。最后，鞘内反义处理敲低雄激素受体减弱了完整雄性大鼠中 NH 的保护作用。总之，这些数据表明雄激素在 NH 诱导的对 WA 应激诱导的肌肉痛觉过敏的弹性中起关键作用。
观点
NH 诱导雄激素依赖性对应激诱导性肌肉疼痛的弹性。因此，雄激素可能导致慢性肌肉骨骼疼痛及其应激增强中观察到的性别差异。
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