Predominant role of spinal P2Y1 receptors in the development of neuropathic pain in rats

Abstract The role of P2X 2/3 , P2X 3 , P2X 4 or P2X 7 and P2Y 2 , P2Y 6 , and P2Y 12 receptors in neuropathic pain has been widely studied. In contrast, the role of P2Y 1 receptors is scarcely studied. In this study we assessed the role of P2Y 1 receptors in several neuropathic pain models in the rat. Furthermore, we analyzed the expression of P2Y 1 receptors in the ipsilateral dorsal root ganglia (DRG) and dorsal part of the spinal cord during the development and maintenance of neuropathic pain. We also determined the effect of the P2Y 1 receptor antagonist on the expression of P2Y 1 receptors. Chronic constriction injury (CCI), spared nerve injury (SNI) or spinal nerve ligation (SNL) produced tactile allodynia from 1 to 14 days after nerve injury. CCI, SNI and SNL enhanced expression of P2Y 1 receptors in DRG but not in the dorsal part of the spinal cord at 1–3 days after injury. Intrathecal injection of the selective P2Y 1 receptor antagonist MRS2500, but not vehicle, reduced tactile allodynia in rats 1–3 days after CCI, SNI, or SNL. Moreover, intrathecal injection of MRS2500 (at day 1 or 3) reduced neuropathy-induced up-regulation of P2Y 1 receptors expression. Intrathecal injection of MRS2500 lost most of the antiallodynic effect when injected 14 days after injury. At this time, MRS2500 did not modify nerve-injury-induced P2Y 1 receptors up-regulation. Our results suggest that P2Y 1 receptors are localized in DRG, are up-regulated by nerve injury and play a pronociceptive role in development and, to a lesser extent, maintenance of neuropathic pain.