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P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury.

Authors: Tsuda, Makoto  Shigemoto-Mogami, Yukari  Koizumi, Schuichi  Mizokoshi, Akito  Kohsaka, Shinichi  Salter, Michael W  Inoue, Kazuhide 
Citation: Tsuda M, etal., Nature. 2003 Aug 14;424(6950):778-83. doi: 10.1038/nature01786.
Pubmed: (View Article at PubMed) PMID:12917686
DOI: Full-text: DOI:10.1038/nature01786

Pain after nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia-pain hypersensitivity evoked by innocuous stimuli. Effective therapy for this pain is lacking, and the underlying mechanisms are poorly understood. Here we report that pharmacological blockade of spinal P2X4 receptors (P2X4Rs), a subtype of ionotropic ATP receptor, reversed tactile allodynia caused by peripheral nerve injury without affecting acute pain behaviours in naive animals. After nerve injury, P2X4R expression increased strikingly in the ipsilateral spinal cord, and P2X4Rs were induced in hyperactive microglia but not in neurons or astrocytes. Intraspinal administration of P2X4R antisense oligodeoxynucleotide decreased the induction of P2X4Rs and suppressed tactile allodynia after nerve injury. Conversely, intraspinal administration of microglia in which P2X4Rs had been induced and stimulated, produced tactile allodynia in naive rats. Taken together, our results demonstrate that activation of P2X4Rs in hyperactive microglia is necessary for tactile allodynia after nerve injury and is sufficient to produce tactile allodynia in normal animals. Thus, blocking P2X4Rs in microglia might be a new therapeutic strategy for pain induced by nerve injury.

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CRRD Object Information
CRRD ID: 13673840
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.