The role of neuron-glia interaction in neuropathic pain

在神经病理性疼痛动物模型中，脊髓小胶质细胞在周围神经损伤后24小时内，其短而粗的突起变得肥大。背角小胶质细胞激活的时间进程与触觉异常痛的发展进程相关。我们还发现小胶质细胞过度表达P2X4受体，并且P2X4刺激小胶质细胞不仅是触觉异常痛所必需的，而且足以引起触觉异常痛(自然，424,778-783,2003)。接下来，我们发现，在神经损伤的大鼠中，维持去极化转变所必需的是P2X_4受体的激活，而刺激P_2X_4可引起小胶质细胞释放BDNF。脑源性神经营养因子本身引起大鼠脊髓神经元内负离子的去极化漂移。阻断P2X4、BDNF的作用可使痛觉异常减轻。这些结果表明，ATP刺激的小胶质细胞通过P2X_4引起LI神经元缩足阈值的降低和E&lt；阴离子&Gt；的漂移都需要BDNF-TrkB信号，而BDNF的来源是小胶质细胞本身(Nature，438,1017-1021)。

In neuropathic pain animal models, spinal microglia become hypertrophic in their short and thick processes within the first 24 hrs after peripheral nerve injury. The time-course of microglial activation in the dorsal horn correlated with that of the development of tactile allodynia. Also we found that the microglia over-expressed P2X4 receptors and that P2X_4 stimulation of microglia is not only necessary for tactile allodynia, but is also sufficient to cause the allodynia (Nature 424,778-783,2003). Next we found that P2X_4 receptor activation is necessary to sustain the depolarizing shift in E_<anion> in rats with nerve injury, and that P2X4 stimulation evoked the release of BDNF from microglia. BDNF itself caused the depolarizing shift in E_<anion> in rat spinal neurons. Blocking the action of P2X4,BDNF caused the reduction of allodynia. These findings show that both the decrease in paw withdrawal threshold and the shift in E_<anion> in LI neurons caused by ATP-stimulated microglia through P2X_4 require BDNF-TrkB signaling and that the source of BDNF is the microglia themselves (Nature,438,1017-1021).