Interactions of purinergic receptors in treating neuropathic pain using electroacupuncture

Abstract

Objective To elucidate the mechanism underlying eletroacupuncture′s (EA′s) amply-documented analgesic effect. To observe its effect on the pain threshold and on the expression of P2X4 receptor and microglia activation in the spinal cords of rats with neuropathic pain. To demonstrate whether or not interfering with A1 receptors and P2X4 receptors at the same time could enhance the analgesic effect. Methods A total of 40 Sprague-Dawley rats weighing 150 to 180 g were randomly divided into a sham group, a CCI group, an EA group, a 2-chloro-N(6)-cyclopentyladenosine (CCPA) group and a CCPA+ EA group, each of 8. Chronic constriction injury (CCI) was induced successfully in the rats of all groups except the sham group. Five days later, EA and 20 μL injections of 0.1 mm/L CCPA were applied to the rat analogues of the Zusanli (ST36) and Yanglingquan (GB34) acupoints once a day for 15 days for the rats in the appropriate groups. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) were measured before the CCI operation and 20 days afterward. L4-L6 spinal cord tissue was then resected and the fluorescence intensity of P2X4 and OX42 receptors was detected using double label immunohistochemical staining. The correlation between the mean fluorescence intensity and the pain threshold gap was analyzed. Results The average MWT and TWL of the CCI group were significantly lower than in the other four groups. The expression of P2X4 receptor and OX42 in the spinal cord increased significantly in the CCI group compared to the other four groups. There was significant correlation between the mean fluorescence intensity of P2X4 and OX42 receptors and the gap in pain threshold, with correlation coefficients of 0.907 and 0.717 respectively. Conclusion P2X4 receptor and microglia activation might be involved in the development of neuropathic pain. CCPA and EA can inhibit the activation of microglia and reduce the activity of P2X4 receptors. The interaction between A1 receptors and P2X4 receptors can strengthen the analgesic effect of EA. Key words: Electroacupuncture; Neuropathic pain; Purinergic receptors; Analgesia