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

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.

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.

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.

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.