小胶质细胞和嘌吟受体在神经病理性疼痛中的作用

The Function of Microglia and Purinergic Receptors in Neuropathic Pain

疾病，感染或损伤等引起的周围神经损害可以造成慢性疼痛状态，有证据表明小胶质细胞在神经病理性疼痛中扮演着重要的角色。小胶质细胞是一种中枢神经系统的免疫活性细胞，可以表达亲离子型P2X4嘌呤受体和亲代谢型P2Y嘌呤受体，周围神经损伤后，脊髓中的小胶质细胞被激活并使P2X4受体的表达增加。新近的研究提示P2X4受体的激活可以引起小胶质细胞产生神经营养因子（BDNF），而这种间接的小胶质神经元释放的信号能够引发痛觉超敏。因此，小胶质细胞中的P2X4受体和细胞内信号介质有望成为神经病理性疼痛治疗的新靶点。

Emerging evidence indicates that microglia play a critical role 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. Microglia are immunocompetent cells of the central nervous system and express various ionotropic P2X and metabotropic P2Y purinoceptors. After injury to a peripheral nerve, microglia in the spinal cord become activated and upregulate expression of the P2X4 receptor. Recent findings suggest that activation of P2X4 receptors evokes release of brain-derived neurotrophic factor from microglia and that this mediates microglia-neuron signaling leading to pain hypersensitivity. Thus, P2X4 receptors and the intracellular signaling mediators in microglia are promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.