Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment disruption. Furthermore, its clinical application is associated with peripheral neuropathy, which always impairs the patient\'s quality of life. Among all P2 receptors, P2Y6 receptor is expressed in rat dorsal spinal cord. However, the role of P2Y6 receptor in the rat CIPN model is still unclear. We evaluated the effect of intrathecal MRS2578 (selective P2Y6 receptor antagonist) on CIPN rats. Additionally, the expression level of P2Y6 receptor in spinal cord and DRG was assessed.
Materials and methods: CIPN was induced by intraperitoneal cisplatin (2 mg/kg/day, 4 consecutive days). Subarachnoid intrathecal catheters were constructed and implanted for drug administration. The behavioral assay was performed to measure the paw withdrawal thresholds (PWT). In addition, the expression of P2Y6 receptor was examined using real time PCR.
Results: Intrathecal MRS2578 significantly increased the paw withdrawal thresholds in CIPN rats. Also, the expression level of P2Y6 receptor was little changed in the spinal cord and DRG of na and CIPN rats.
Conclusion: The P2Y6 receptor antagonist MRS2578 has antiallodynic effect in the CIPN rats. Therefore, it can be provided as a potential target in the treatment of CIPN.