Effect of Exercise on µ-Opioid Receptor Expression in the Rostral Ventromedial Medulla in Neuropathic Pain Rat Model

OBJECTIVE To investigate the effects of aerobic exercise on neuropathic pain and verify whether regular treadmill exercise alters opioid receptor expression in the rostral ventral medulla (RVM) in a neuropathic pain rat model. METHODS Thirty-two male Sprague-Dawley rats were used in the study. All rats were divided into 3 groups, i.e., group A, sham group (n=10); group B, chronic constriction injury (CCI) group (n=11); and group C, CCI+exercise group (n=11). Regular treadmill exercise was performed for 30 minutes a day, 5 days a week, for 4 weeks at the speed of 8 m/min for 5 minutes, 11 m/min for 5 minutes, and 22 m/min for 20 minutes. Withdrawal threshold and withdrawal latency were measured before and after the regular exercise program. Immunohistochemistry and Western blots analyses were performed using antibodies against µ-opioid receptor (MOR). RESULTS Body weight of group C was the lowest among all groups. Withdrawal thresholds and withdrawal latencies were increased with time in groups B and C. There were significant differences of withdrawal thresholds between group B and group C at 1st, 2nd, 3rd, and 4th weeks after exercise. There were significant differences of withdrawal latencies between group B and group C at 3rd and 4th weeks after exercise. MOR expression of group C was significantly decreased, as compared to that of group B in the RVM and spinal cord. CONCLUSION In neuropathic pain, exercise induced analgesia could be mediated by desensitization of central MOR by endogenous opioids, leading to the shift of RVM circuitry balance to pain inhibition.