RT Journal Article
SR Electronic
T1 Up-Regulation of P2X<sub>4</sub> Receptors in Spinal Microglia after Peripheral Nerve Injury Mediates BDNF Release and Neuropathic Pain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 11263
OP 11268
DO 10.1523/JNEUROSCI.2308-08.2008
VO 28
IS 44
A1 Ulmann, Lauriane
A1 Hatcher, Jon P.
A1 Hughes, Jane P.
A1 Chaumont, Séverine
A1 Green, Paula J.
A1 Conquet, François
A1 Buell, Gary N.
A1 Reeve, Alison J.
A1 Chessell, Iain P.
A1 Rassendren, Francois
YR 2008
UL http://www.jneurosci.org/content/28/44/11263.abstract
AB ATP is a known mediator of inflammatory and neuropathic pain. However, the mechanisms by which specific purinergic receptors contribute to chronic pain states are still poorly characterized. Here, we demonstrate that in response to peripheral nerve injury, P2X4 receptors (P2X4R) are expressed de novo by activated microglia in the spinal cord. Using in vitro and in vivo models, we provide direct evidence that P2X4R stimulation leads to the release of BDNF from activated microglia and, most likely phosphorylation of the NR1 subunit of NMDA receptors in dorsal horn neurons of the spinal cord. Consistent with these findings, P2X4-deficient mice lack mechanical hyperalgesia induced by peripheral nerve injury and display impaired BDNF signaling in the spinal cord. Furthermore, ATP stimulation is unable to stimulate BDNF release from P2X4-deficient mice microglia in primary cultures. These results indicate that P2X4R contribute to chronic pain through a central inflammatory pathway. P2X4R might thus represent a potential therapeutic target to limit microglia-mediated inflammatory responses associated with brain injury and neurodegenerative disorders.