TY - JOUR
T1 - P2X4 receptors and neuropathic pain
AU - Tsuda, Makoto
AU - Masuda, Takahiro
AU - Tozaki-Saitoh, Hidetoshi
AU - Inoue, Kazuhide
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/10/28
Y1 - 2013/10/28
N2 - Neuropathic pain, a debilitating pain condition, is a common consequence of damage to the nervous system. Neuropathic pain is often resistant to currently available analgesics. A growing body of evidence indicates that spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve injury, P2X4 receptors (P2X4Rs) are upregulated in spinal microglia by several factors at the transcriptional and translational levels. Those include the CC chemokine CCL21 derived from damaged neurons, the extracellular matrix protein flbronectin in the spinal cord, and the transcription factor interferon regulatory factor 8 (IRF8) expressed in microglia. P2X4R expression in microglia is also regulated at the post-translational level by signaling from other cell-surface receptors such as CC chemokine receptor (CCR2). Importantly, inhibiting the function or expression of P2X4Rs and P2X4R-regulating molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings indicate that P2X4R-positive microglia are a central player in mechanisms for neuropathic pain. Thus, microglial P2X4Rs are a potential target for treating the chronic pain state.
AB - Neuropathic pain, a debilitating pain condition, is a common consequence of damage to the nervous system. Neuropathic pain is often resistant to currently available analgesics. A growing body of evidence indicates that spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve injury, P2X4 receptors (P2X4Rs) are upregulated in spinal microglia by several factors at the transcriptional and translational levels. Those include the CC chemokine CCL21 derived from damaged neurons, the extracellular matrix protein flbronectin in the spinal cord, and the transcription factor interferon regulatory factor 8 (IRF8) expressed in microglia. P2X4R expression in microglia is also regulated at the post-translational level by signaling from other cell-surface receptors such as CC chemokine receptor (CCR2). Importantly, inhibiting the function or expression of P2X4Rs and P2X4R-regulating molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings indicate that P2X4R-positive microglia are a central player in mechanisms for neuropathic pain. Thus, microglial P2X4Rs are a potential target for treating the chronic pain state.
UR - http://www.scopus.com/inward/record.url?scp=84886831566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886831566&partnerID=8YFLogxK
U2 - 10.3389/fncel.2013.00191
DO - 10.3389/fncel.2013.00191
M3 - Review article
AN - SCOPUS:84886831566
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
IS - OCT
M1 - 191
ER -