Behavioral phenotypes of mice lacking purinergic P2X<sub>4 </sub>receptors in acute and chronic pain assays
<p>Abstract</p> <p>A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X<sub>3</sub>R subtype that has been e...
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| Main Authors: | , , , , , |
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| Format: | Book |
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SAGE Publishing,
2009-06-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X<sub>3</sub>R subtype that has been extensively studied, the precise roles of others among the seven P2XR subtypes (P2X<sub>1</sub>R-P2X<sub>7</sub>R) remain to be determined because of a lack of sufficiently powerful tools to specifically block P2XR signaling <it>in vivo</it>. In the present study, we investigated the behavioral phenotypes of a line of mice in which the <it>p2rx4 </it>gene was disrupted in a series of acute and chronic pain assays. While <it>p2rx4</it><sup>-/- </sup>mice showed no major defects in pain responses evoked by acute noxious stimuli and local tissue damage or in motor function as compared with wild-type mice, these mice displayed reduced pain responses in two models of chronic pain (inflammatory and neuropathic pain). In a model of chronic inflammatory pain developed by intraplantar injection of complete Freund's adjuvant (CFA), <it>p2rx4</it><sup>-/- </sup>mice exhibited attenuations of pain hypersensitivity to innocuous mechanical stimuli (tactile allodynia) and also of the CFA-induced swelling of the hindpaw. A most striking phenotype was observed in a test of neuropathic pain: tactile allodynia caused by an injury to spinal nerve was markedly blunted in <it>p2rx4</it><sup>-/- </sup>mice. By contrast, pain hypersensitivity to a cold stimulus (cold allodynia) after the injury was comparable in wild-type and <it>p2rx4</it><sup>-/- </sup>mice. Together, these findings reveal a predominant contribution of P2X<sub>4</sub>R to nerve injury-induced tactile allodynia and, to the lesser extent, peripheral inflammation. Loss of P2X<sub>4</sub>R produced no defects in acute physiological pain or tissue damaged-induced pain, highlighting the possibility of a therapeutic benefit of blocking P2X<sub>4</sub>R in the treatment of chronic pain, especially tactile allodynia after nerve injury.</p> |
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| Item Description: | 10.1186/1744-8069-5-28 1744-8069 |