Combined effect of chronic progesterone administration with compulsive exercise on prevention of TNF-α production and abnormal electrophysiological responses of sciatic nerve in Chronic Constriction injury pain model in rat

Introduction: Neuropathic pain has no definitive treatment and the socio-economic status and personality of patient is severely affected. Since the exercise and/or progesterone effect on Chronic Constriction injury (CCI) neuropathic pain has been studied and each individually have been able to improve neuropathic pain and as a part of its etiology is related to TNF-α production, we tried to test these factors on TNF-α production and electrophysiologic responses of sciatic nerve in neuropathic pain model in rat. Materials and Methods: 50 male Wistar rats were used in 5 groups. Experimental groups were including: 1- Sham,   2- CCI + Vehicle (VEH), 3- CCI + VEH + Exercise,   4- CCI + Progestrone and 5- CCI + Progestrtone + Exercise. The sciatic nerve CCI model of rat was used to induce chronic neuropathic pain in the respective groups. Some groups of animals treated by progesterone injections (6 mg/kg) or its vehicle from day 1 to day 12 after surgery. The exercise was started two weeks before surgery and again, one-week after that and lasted to day 12. Electrophysiological tests and blood sampling were done on day 13. Results: The results showed that co administration of progesterone for 12 days and moderate intensity exercise for 3 weeks before complete neuropathic pain evolution could prevent significantly TNF-α production and electrophysiologic (Tibial and sural nerve conduction velocity) abnormality compared to the CCI group as well as compared to the exercise or progesterone group alone. Conclusion: The findings of this study showed that co-administration of progesterone and forced exercise before neuropathy development may prevent TNF-α production and neuropathic disease. Also, the results showed that the effects of co-administration of progesterone and forced exercise in preventing electrophysiologic abnormality may be additive.