Early-life stress produces muscle hyperalgesia and nociceptor sensitization in the adult rat
Early-life stress produces muscle hyperalgesia and nociceptor sensitization in the adult rat
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DOI：
10.1016/j.pain.2011.07.021
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发表时间：
2011-11-01
期刊：
影响因子：
7.4
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
--
作者：
Green, Paul G.;Chen, Xiaojie;Levine, Jon D.
成年人的慢性疼痛与早期生活压力有关。为了研究生命早期应激的原伤害感受效应，我们在大鼠的新生儿应激动物模型中评估了皮肤和肌肉伤害感受和肌肉伤害感受器的活性。在该新生儿有限垫料（NLB）模型中，窝仔在出生后第2 - 9天暴露于有限垫料，对照组暴露于标准垫料。在成年NLB治疗的大鼠，骨骼肌的机械伤害性阈值显着低于（类似于22%）比对照组。此外，在皮肤和肌肉中给予前列腺素E-2可产生明显延长的痛觉过敏，脊髓鞘内注射蛋白激酶C β（PKC β）反义寡脱氧核苷酸可防止这种效应，PKC β是伤害感受器中的第二信使，与慢性疼痛的诱导和维持有关。在电生理研究中，肌肉伤害感受器的机械阈值降低了约31%，传导速度显著增加（约28%）。这些研究结果表明，新生儿应激诱导持续性痛觉过敏和伤害感受器敏化表现在成人和第二信使PKCe可能是一个目标，针对该疗法可能是针对治疗慢性疼痛综合征，这是与早期生活创伤应激。(C)2011年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
Chronic pain in adults has been associated with early-life stress. To examine the pronociceptive effect of early-life stress, we evaluated cutaneous and muscle nociception and activity in muscle nociceptors in an animal model of neonatal stress, limited bedding, in the rat. In this neonatal limited bedding (NLB) model, litters are exposed to limited bedding between postnatal days 2 and 9, and controls to standard bedding. In adult NLB-treated rats, mechanical nociceptive threshold in skeletal muscle was significantly lower (similar to 22%) than in controls. Furthermore, administration of prostaglandin E-2 in skin as well as muscle produced markedly prolonged hyperalgesia, an effect prevented by spinal intrathecal injection of oligode-oxynucleotide antisense to protein kinase C epsilon (PKC epsilon), a second messenger in nociceptors that has been implicated in the induction and maintenance of chronic pain. In electrophysiological studies, mechanical threshold of muscle nociceptors was reduced by similar to 31% and conduction velocity significantly increased (similar to 28%). These findings indicate that neonatal stress induces a persistent hyperalgesia and nociceptor sensitization manifest in the adult and that the second messenger PKCe may be a target against which therapies might be directed to treat a chronic pain syndrome that is associated with early-life traumatic stress. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.