P2X4R+ microglia drive neuropathic pain

被引：287

作者：

Beggs, Simon ^{[1
,2
,3
]}

Trang, Tuan ^{[1
,2
,4
]}

Salter, Michael W. ^{[1
,2
,3
,4
]}

机构：

[1] Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada

[2] Univ Toronto, Ctr Study Pain, Toronto, ON, Canada

[3] Univ Toronto, Fac Dent, Toronto, ON, Canada

[4] Univ Turin, Fac Med, Dept Phys, Toronto, ON, Canada

来源：

NATURE NEUROSCIENCE | 2012年 / 15卷 / 08期

基金：

加拿大健康研究院;

关键词：

PERIPHERAL-NERVE INJURY; LAMINA-I NEURONS; RECEPTOR UP-REGULATION; CNS GLIAL MODULATOR; SPINAL MICROGLIA; P2X(4) RECEPTORS; DIFFERENTIAL RESPONSES; RODENT MICROGLIA; ANION GRADIENT; VITRO EVIDENCE;

D O I：

10.1038/nn.3155

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neuropathic pain, the most debilitating of all clinical pain syndromes, may be a consequence of trauma, infection or pathology from diseases that affect peripheral nerves. Here we provide a framework for understanding the spinal mechanisms of neuropathic pain as distinct from those of acute pain or inflammatory pain. Recent work suggests that a specific microglia response phenotype characterized by de novo expression of the purinergic receptor P2X4 is critical for the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Stimulating P2X4 receptors initiates a core pain signaling pathway mediated by release of brain-derived neurotrophic factor, which produces a disinhibitory increase in intracellular chloride in nociceptive (pain-transmitting) neurons in the spinal dorsal horn. The changes caused by signaling from P2X4R(+) microglia to nociceptive transmission neurons may account for the main symptoms of neuropathic pain in humans, and they point to specific interventions to alleviate this debilitating condition.

引用

页码：1068 / 1073

页数：6