Forced exercise attenuates neuropathic pain in chronic constriction injury of male rat: an investigation of oxidative stress and inflammation

Abstract

Hossein Ali Safakhah,1,2 Nasroallah Moradi Kor,2,3 Atiyeh Bazargani,3 Ahmad Reza Bandegi,4 Hamid Gholami Pourbadie,5 Baharak Khoshkholgh-Sima,5 Ali Ghanbari2 1Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; 2Research Center of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; 3Student Research Committee, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; 4Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; 5Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran Background and objective: Initial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve.Materials and methods: Wistar male rats weighing 200±20 g were randomly divided into five groups (normal, sham, CCI, pre-CCI exercise, and post-CCI exercise group). Sciatic nerve of anesthetized rats was loosely ligated to induce CCI, and they were then housed in separate cages. The rats ran on treadmill at a moderate speed for 3 weeks. Mechanical allodynia and thermal hyperalgesia were determined using von Frey filament and plantar test, respectively. Tumor necrosis factor-alpha (TNF-α) assayed in the cerebrospinal fluid, malondialdehyde, and total antioxidant capacity were measured in the serum using Western blot test, thiobarbituric acid, and ferric reducing ability of plasma (FRAP), respectively.Results: The mechanical allodynia (P=0.024) and thermal hyperalgesia (P=0.002) in the CCI group were higher than those in the sham group. Exercise after CCI reduced (P=0.004) mechanical allodynia and thermal hyperalgesia (P=0.025) compared with the CCI group. Moreover, the level of FRAP in the CCI group was (P=0.001) lower than that in the sham group, and post-CCI exercise reversed FRAP amount toward the control level (P=0.019). The amount of malondialdehyde did not differ between groups. Level of TNF-α increased in the CCI group (P=0.0002) compared with sham group and post-CCI exercise could reverse it toward the level of control (P=0.005).Conclusion: Post CCI-exercise but not pre CCI-exercise reduces CCI-induced neuropathic pain. One of the possible involved mechanisms is increasing the total antioxidant capacity and reducing the amount of TNF-α. Keywords: CCI, TNF-α, treadmill exercise, neuropathic pain, oxidative stress 

Keywords

• CCI
• TNF-α
• treadmill exercise
• neuropathic pain
• oxidative stress