ATP receptors gate microglia signaling in neuropathic pain
ATP receptors gate microglia signaling in neuropathic pain
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DOI：
10.1016/j.expneurol.2011.11.012
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发表时间：
2012-04
影响因子：
5.3
通讯作者：
T. Trang;S. Beggs;M. Salter
中科院分区：
文献类型：
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作者：
T. Trang;S. Beggs;M. Salter
Pio del Rio-Hortega (1932) 将小胶质细胞描述为区别于神经元和星形胶质细胞的“第三要素”。在这一观察发生几十年后，小胶质细胞作为一种独特的细胞类型的功能甚至其存在本身就成为了激烈争论和猜想的话题。然而，在了解小胶质细胞的神经生物学方面已经取得了相当大的进展，导致我们对小胶质细胞的看法发生了根本性的转变，它们从只具有免疫和支持作用的被动旁观者，转变为导致疾病或损伤后引起的中枢神经系统病理的主动主要参与者。各种证据表明，小胶质细胞在神经性疼痛的发病机制中至关重要，神经性疼痛是一种使人衰弱的慢性疼痛，可能发生在疾病、感染或身体损伤引起的周围神经损伤后。调节小胶质细胞活性的关键分子是 ATP，它是 P2-嘌呤受体家族的内源性配体，由 P2X 离子型受体和 P2Y 代谢型受体组成。小胶质细胞表达多种 P2 受体亚型，其中 P2X4、P2X7 和 P2Y12 受体亚型与神经性疼痛有关。 P2X4 受体已成为核心的小胶质细胞-神经元信号传导通路：该受体的激活会导致脑源性神经营养因子 (BDNF) 的释放，从而导致 I 椎板中疼痛传递神经元的去抑制。本综述重点介绍了了解小胶质细胞中表达的 P2 受体的信号传导和调节的最新进展，以及小胶质细胞-神经元相互作用对神经病理性疼痛治疗的影响。
Microglia were described by Pio del Rio-Hortega (1932) as being the ‘third element’ distinct from neurons and astrocytes. Decades after this observation, the function and even the very existence of microglia as a distinct cell type were topics of intense debate and conjecture. However, considerable advances have been made towards understanding the neurobiology of microglia resulting in a radical shift in our view of them as being passive bystanders that have solely immune and supportive roles, to being active principal players that contribute to central nervous system pathologies caused by disease or following injury. Converging lines of evidence implicate microglia as being essential in the pathogenesis of neuropathic pain, a debilitating chronic pain condition that can occur after peripheral nerve damage caused by disease, infection, or physical injury. A key molecule that modulates microglial activity is ATP, an endogenous ligand of the P2-purinoceptor family consisting of P2X ionotropic and P2Y metabotropic receptors. Microglia express several P2 receptor subtypes, and of these the P2X4, P2X7, and P2Y12 receptor subtypes have been implicated in neuropathic pain. The P2X4 receptor has emerged as the core microglia–neuron signaling pathway: activation of this receptor causes release of brain-derived neurotrophic factor (BDNF) which causes disinhibition of pain-transmission neurons in spinal lamina I. The present review highlights recent advances in understanding the signaling and regulation of P2 receptors expressed in microglia and the implications for microglia–neuron interactions for the management of neuropathic pain.