P2X4 receptors of microglia in neuropathic pain.

We have learned various data on the role of purinoceptors (P2X4, P2X7, P2Y6 and P2Y12 receptors) expressed in spinal microglia and several factors that presumably activate microglia in neuropathic pain after peripheral nerve injury. Especially P2X4 receptors (P2X4Rs) make a critical contribution to the pain processing. P2X4Rs of microglia might be promising targets for treating neuropathic pain. A predicted therapeutic benefit of interfering with microglial P2X4Rs may be that normal pain sensitivity would be unaffected since expression or activity of most of these receptors are upregulated or enhanced predominantly in activated microglia in the spinal cord where damaged sensory fibers project. Recently, we found that CCL21 regulates the expression of P2X4Rs in different manners, respectively. These new findings also provide novel targets for developing anti-neuropathic pain medicines.