Functional up-regulation of P2X3 receptors in the chronically compressed dorsal root ganglion

P2X receptors on dorsal root ganglion (DRG) neurons have been strongly implicated in pathological nociception after peripheral nerve injuries of inflammation. However, nothing is known of a role for purinergic receptors in neuropathic pain produced by a chronic compression of DRG (CCD) - an injury that may accompany an intraforaminal stenosisi, a laterally herniated disc or other disorders of the spine leading to radicular pain. In a rat model of DRG compression, hyperexcitable neurons retain functioning axonal connections with their peripheral targets. It is unknown whether such hyperexicitability might enhance chemically mediated nociceptive stimulation of the skin. In this study, CCD faciliated the nocifensive behavior and mechanical hyperalgasia-induced by the P2X(3) agonist. alpha,beta-methylene ATP (alpha,beta-meATP). An injection of alpha,beta-mATP into the hind paw of CCD rats resulted in a significantly greater decrease in the mean threshold to von Frey stimuli and a greater duration of paw lifts than in sham-operated control rats. CCD also increased the levels of P2X(3) receptors were co-labeled with the isolectin IB4, consistent with a role in noiception. In addition, a alpha,beta-meATP induced significantly larger fast-inactivating currents in CCD- than in sham-operated acutely disocciated DRG neurons. These currents were accompanied by the generation of action potentials but only in the CCD neurons. U0126 a specific inhibitor of the ME/K1/2. greatly down-regulated the enhanced current. Take together, these observations suggest that enhanced puringetic responses after CCD are mediated by P2X(3) receptors. (C) 2008 International Association for the Study of Pain, Published by Elsevier B.V. All rights reserved.