The Effect of Aerobic Exercise and Melatonin on COX-2 Gene Expression in Spinal Cord Tissue and Neuropathic Pain Behavioral Responses in a Diabetic Rat Model

Introduction: Neuroinflammation plays an important role in developing many neurological changes in diabetic patients. This study aimed to investigate the effect of aerobic exercise and melatonin on COX-2 expression in spinal cord tissue and behavioral responses to pain caused by diabetic neuropathy in a rat model. Materials and Methods: Forty eight-week-old male Wistar rats (weight range 204 ± 11.3 g) were randomly divided into five groups of eight, including diabetic neuropathy (50 mg/kg streptozotocin intraperitoneal injection), diabetic neuropathy with melatonin administration (10 mg/kg  melatonin daily for six weeks), diabetic neuropathy with exercise (30 minutes of aerobic exercise at 15 meters per minute, five days a week for six weeks), diabetic neuropathy with melatonin administration and exercise, and controls. After confirmation of diabetic neuropathy with behavioral tests, the exercising and melatonin administration protocol was performed. The COX-2 gene expression level in spinal cord tissue was measured using the real-time technique. Also, one-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Results: Exercise and melatonin decreased the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia in the diabetic neuropathy with melatonin administration and exercise group (P =0.026). Also, the COX-2 gene expression level was significantly reduced in this group compared to the diabetic neuropathy group (P=0.001). Conclusion: Aerobic exercise with melatonin injection modulates the COX-2 gene expression level and improves the sensitivity of nociceptors to pathogens. Aerobic exercise and melatonin administration are recommended for neuropathic pain in people with diabetes.