Glial activation and pathological pain
Glial activation and pathological pain
复制标题
DOI：
10.1016/j.neuint.2003.09.009
复制
发表时间：
2004-07-01
影响因子：
4.2
通讯作者：
Watkins, LR
中科院分区：
文献类型：
--
作者：
Wieseler-Frank, J;Maier, SF;Watkins, LR
疼痛是一种我们都经历过的感觉。对我们大多数人来说，痛苦是暂时的。然而，对于患有病理性疼痛的患者，疼痛体验是无止境的，几乎没有治疗缓解的希望。病理性疼痛的特征在于对正常无害刺激的放大反应和对急性疼痛的放大反应。病理性疼痛长期以来被描述为功能失调的神经元活动的结果。虽然神经元功能确实发生了改变，但有重要证据表明，过度疼痛是由星形胶质细胞和小胶质细胞的激活调节的。在过度疼痛中，星形胶质细胞和小胶质细胞被神经元信号激活，包括P物质，谷氨酸和fractalkine。这些物质激活神经胶质细胞导致介质的释放，然后作用于其他神经胶质细胞和神经元。这些包括一个被称为“促炎细胞因子”的蛋白质家族，它们从小胶质细胞和星形胶质细胞中释放出来。这些细胞因子已被证明是夸大疼痛的关键介质。一些病理性疼痛患者也报告“域外”和/或“镜像”疼痛。也就是说，夸大的疼痛不仅在创伤区域经历。在域外疼痛中，疼痛也被认为是由创伤部位以外的邻近健康组织引起的。在镜像疼痛的罕见病例中，这种疼痛被认为是由身体另一侧的健康的相应身体部位引起的。新的数据表明，通过缝隙连接激活星形胶质细胞通讯可能介导这种疼痛的传播。虽然病理性疼痛的传统疗法集中在神经元靶点，但以下综述将神经胶质描述为新认识到的夸大疼痛的介质和新的治疗靶点。此外，这里讨论的神经胶质-神经元相互作用可能不仅限于疼痛，而且可能在其他行为现象中发挥重要作用。(C)2003 Elsevier Ltd.保留所有权利。
Pain is a sensation we have all experienced. For most of us, the pain has been temporary. However, for patients with pathological pain, the pain experience is unending, with little hope for therapeutic relief. Pathological pain is characterized by an amplified response to normally innocuous stimuli, and an amplified response to acute pain. Pathological pain has long been described as the result of dysfunctional neuronal activity. While neuronal functioning is indeed altered, there is significant evidence showing that exaggerated pain is regulated by the activation of astrocytes and microglia. In exaggerated pain, astrocytes, and microglia are activated by neuronal signals including substance P, glutamate, and fractalkine. Activation of glia by these substances leads to the release of mediators that then act on other glia and neurons. These include a family of proteins called "proinflammatory cytokines" released from microglia and astrocytes. These cytokines have been shown to be critical mediators of exaggerated pain. Some patients with pathological pain also report "extra-territorial" and/or "mirror" image pain. That is, exaggerated pain is experienced not only in the area of trauma. In extra-territorial pain, pain is also perceived as arising from neighboring healthy tissues outside of the site of trauma. In the rare cases of mirror-image pain, such pain is perceived as arising from the healthy, corresponding body part on the opposite side of the body. New data suggest that activation of astrocyte communication via gap junctions may mediate such spread of pain. While traditional therapies for pathological pain have focused on neuronal targets, the following review describes glia as newly recognized mediators of exaggerated pain, and as new therapeutic targets. Moreover, the glial-neuronal interactions discussed here are likely not exclusive to pain, but rather are likely to play significant roles in other behavioral phenomena. (C) 2003 Elsevier Ltd. All rights reserved.