Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells

Author: Paulino Barragán-Iglesias

The participation of spinal P2X receptors in pain neuropathic is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors.
Spinal administration of the selective P2Y6 (MRS2578, 10-100 muM) and P2Y11 (NF340, 0.3-30 muM) receptors antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury. Furthermore, intrathecal administration of MRS2578 (100 muM/day) and NF340 (30 muM/day) for 3 days significantly reduced spinal nerve injury-induced increase in P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after injury) with minocycline (100 mug/day) or fluorocitrate (1 nmol/day) for 7 days reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1 and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up-regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury) with the selective P2Y6 (PSB0474, 3-30 muM) and P2Y11 (NF546, 1-10 muM) receptor agonists produced remarkable tactile allodynia in nerve ligated rats previously treated with minocycline or fluorocitrate for 7 days.
Our data suggest that spinal P2Y6 receptors acould be present in spinal microglia while P2Y11 receptors could be present in both spinal microglia and astrocytes." to "Our data suggest that spinal P2Y6,11 receptors are present in spinal microglia while P2Y11 receptors are present only in astrocytes.
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