Neurosciences & Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada.
Nat Neurosci. 2012 Jul 26;15(8):1068-73. doi: 10.1038/nn.3155.
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.
神经性疼痛是所有临床疼痛综合征中最使人虚弱的一种，可能是创伤、感染或影响外周神经的疾病导致的结果。在这里，我们提供了一个理解神经性疼痛的脊髓机制的框架，该机制与急性疼痛或炎症性疼痛的机制不同。最近的研究表明，一种特定的小胶质细胞反应表型，其特征是嘌呤能受体 P2X4 的从头表达，对于由外周神经损伤引起的疼痛敏感性增加的发病机制至关重要。刺激 P2X4 受体启动了由脑源性神经营养因子释放介导的核心疼痛信号通路，该通路在脊髓背角的伤害感受（疼痛传递）神经元中产生抑制性氯离子内流增加。由 P2X4R(+)小胶质细胞向伤害感受神经元传递信号引起的变化可能解释了人类神经性疼痛的主要症状，并且它们指向了缓解这种使人虚弱的疾病的具体干预措施。
