Introduction: In this study, we investigated the hypothesis of whether short term and moderate intense treadmill exercise could lead to a sustained reversal of peripheral neuropathy induced cold aversion by activation of endogenous opioidergic systems.
 
Materials & Methods: The tibial nerve transection (TNT) was performed in the anesthetized rats. 28 days after TNT surgery, the animals were randomized to three sedentary and four treadmill exercise (14 days, 30 min/day with max speed of 1.2 Km/h) groups. Animal activity and thermal preference behavior were determined by double plate technique (thermo-neutral plate: 24 ºC and cold plate: 14 ºC), equipped with a video tracking software. For determination of opioidergic system involvement, intraperitoneal injection of naltroxone (2 mg/kg) was done before exercise. Morphine (2.5 mg/kg) and naloxone (1 mg/kg) were also used exactly after the end of the last session of exercise.
 
Findings: Tibial nerve transection significantly decreased the animals’ activities (P<0.001), the time spent in cold plate (P<0.002) and increased escape index from the cold plate (E.I), (P<0.0001), in comparison with intact animals. Treadmill exercise significantly prevented cold allodynia (P<0.002), increased animal activity (P<0.01) and decreased E.I (P<0.0001) 42 days after TNT surgery. Administration of morphine in the both exercised and none-exercised groups significantly reduced E.I., (P<0.0001). Injection of naltrexone before exercise training or naloxone immediately after exercise prevented anti-allodynia effect of exercise on the exercise trained animals.
 
Discussion & Conclusion: Our investigation came to the conclusion that a short period of moderate aerobic exercise could reduce cold aversion and improve animal locomotor activity after peripheral neuropathy via activation of opioidergic system.