Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats
Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats
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DOI：
10.1016/j.jpain.2018.01.009
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发表时间：
2018-06-01
期刊：
影响因子：
4
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
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作者：
Alvarez, Pedro;Green, Paul G.;Levine, Jon D.
新生处理（NH）的雄性大鼠幼仔强烈减弱应激反应和应激诱导的持续性肌肉痛觉过敏的成年人。由于女性性别是一个公认的风险因素，压力引起的慢性肌肉疼痛，我们探讨了NH是否提供弹性的压力引起的痛觉过敏的成年雌性大鼠。幼鼠接受NH或标准（对照）护理。成年后，在避水（WA）应激前后评估肌肉机械伤害性阈值。与雄性大鼠相比，NH只产生了适度的保护作用，对WA应激诱导的肌肉痛觉过敏的雌性大鼠。性腺切除术完全废除NH诱导的弹性在雄性大鼠，但只产生一个小的增加，这种保护作用在雌性大鼠。除了性腺切除术外，抗雌激素药物氟维司群的给药并未增强NH对雌性大鼠的保护作用。最后，敲低雄激素受体的鞘内反义治疗衰减的保护作用，NH在完整的雄性大鼠。总之，这些数据表明，雄激素在NH诱导的恢复力WA应力诱导的肌肉hyperalgesia.Perspective的关键作用：NH诱导雄激素依赖的恢复力应力诱导的肌肉疼痛。因此，雄激素可能有助于观察到的慢性肌肉骨骼疼痛的性别差异和压力的增强。(C)2018年美国疼痛协会American Pain Society
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. (C) 2018 by the American Pain Society