The role of neuron-glia interaction in neuropathic pain

点击翻译按钮获取中文摘要

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).