title: [Mechanisms underlying the pathogenesis of neuropathic pain revealing by the role of glial cells].
abstract: Injury to the nervous system results in debilitating chronic pain states (called neuropathic pain) whose mechanisms remain unclear. Emerging lines of evidence indicate the pivotal role of spinal glial cells in neuropathic pain. Spinal microglia rapidly respond to peripheral nerve injury (PNI) and become activated with changing expression of a variety of genes. The best known example is purinergic P2X4 receptors, an ATP-gated cation channel. The expression of P2X4 receptors is upregulated in spinal microglia after PNI, and inhibition of P2X4 activity suppresses neuropathic pain. Furthermore, interferon regulatory factor-8 (IRF8) and IRF5 are identified as microglial transcription factors whose expression is upregulated in spinal microglia after PNI, and the IRF8-IRF5 transcriptional cascade is the core process for shifting spinal microglia toward a state with high expression of P2X4 receptors. Astrocytes in the spinal cord show a delayed onset of activation and play an important role in the maintenance of neuropathic pain via the transcription factor STAT3 and the intracellular kinase JNK. These results obtained from glial cell research will advance our understanding of the development and maintenance of neuropathic pain and provide a new target for treating this pain.
authors: Makoto
authors: M
authors: Tsuda
mesh_terms: D000818:Animals; D015870:Gene Expression; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D017628:Microglia / Q000378:metabolism / Q000502:physiology; D009437:Neuralgia / Q000209:etiology* / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000235:genetics; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2 / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor; D013116:Spinal Cord / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D048670:MAP Kinase Kinase 4; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C431713:IRF5 protein, human; C494086:STAT3 protein, human