The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats.

Abstract

To explore the role of P2Y6 receptors in the maintenance of neuropathic pain and progression of oxidative stress, we investigated the efficacy of the selective P2Y6 receptors antagonist MRS2578 on the antiallodynic effects and improvement of pathological neuropathic pain-induced oxidative stress, thereby finding a potential therapeutic target in neurological disease. The mechanical allodynia in the ipsilateral spinal dorsal horn (SDH) of rats was observed in rats after chronic constriction injury (CCI). Meanwhile, the messenger RNA (mRNA) levels of biological parameters, including superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1) in the SDH of rats were measured by real-time polymerase chain reaction (RT-PCR). In addition, the mRNA expression and protein levels of P2Y6 were measured by RT-PCR and Western blot assay, respectively. Next, the rats subjected to CCI were intrathecally infused with MRS2578 to block the expression of P2Y6 receptors. The positive expression of P2Y6 receptors was examined by immunohistochemistry. In the present study, the results revealed that the P2Y6 expression in the ipsilateral SDH of CCI rats was significantly upregulated. In addition, inhibition of the P2Y6 receptor in SDH increased CCI-induced tactile allodynia. Furthermore, the levels of SOD, GSH, and HO-1 which were correlated with oxidative stress produced by CCI were also decreased. The results demonstrated that inhibition of the P2Y6 receptor can generate antiallodynic effects and improved the pathological neuropathic pain-induced oxidative stress. Thus, this study provides a potential approach for the therapy of neurological disease.