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Purinergic signaling in spinal cord microglia plays an important role in the pathogenesis of neuropathic pain. Among all P2 receptors, P2Y 6 receptor is expressed in rat dorsal spinal cord. However, it's not clear that the role of P2Y 6 receptor in the chronic constriction injury (CCI) model of neuropathic pain rats. We evaluated the effect of repeated intrathecal administration of MRS2578 (selective P2Y 6 receptor antagonist) on CCI-induced nociceptive behaviors in rats. After CCI, MRS2578 (10 -11 -10 -4  M) was administration. The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were assessed. The expression of P2Y 6 receptor and Iba-1 at rat dorsal spinal cord was observed by using RT-PCR. We found that intrathecal injection of MRS2578 suppressed CCI-induced mechanical allodynia and thermal hyperalgesia with a dose-dependent manner. The CCI rats presented increased expression of P2Y 6 receptor and Iba-1 at the mRNA level in the ipsilateral dorsal spinal cord than that in sham group. Treatment with either minocycline or SB203580 effectively inhibited P2Y 6 receptor expression compared to CCI rats. Intrathecal injection of UDP enhanced mechanical and thermal allodynia than that in CCI group. To the further study, intrathecal injection of UDP causes mechanical allodynia and thermal hyperalgesia in naive rats. The increased expression of P2Y 6 receptor and Iba-1 were observed in UDP-treated rats. Intrathecal injection of MRS2578 alleviates pain response in UDP-treated rats. These observations suggested that P2Y 6 receptor in dorsal spinal cord contribute to mechanical allodynia and thermal hyperalgesia in CCI-induced neuropathic pain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Accumulating evidence indicates that various subtypes of purinergic receptors (P2X and P2Y receptor families) play an essential role in the development and the maintenance of neuropathic pain. However, there is only limited data available about the role of P2Y6 receptors in pain processing. Here we detected P2Y6 receptor immunoreactivity in primary afferent neurons of mice and observed an upregulation in response to peripheral nerve injury. However, systemic and intrathecal administration of the P2Y6 receptor antagonist MRS2578 failed to affect the injury-induced neuropathic pain behavior. Our results suggest that P2Y6 receptors, in contrast to other purinergic receptor subtypes, are not critically involved in nerve injury-induced neuropathic pain processing in mice., (Copyright © 2014 Elsevier Inc. All rights reserved.)