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

Abstract

Background and objectiveInitial 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 methodsWistar 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.ResultsThe 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).ConclusionPost 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.

Hypoalgesic effect of Spirulina platensis on the sciatic neuropathic pain induced by chronic constriction injury in male rats

“…Our results revealed that CCI leads to mechanical allodynia and thermal hyperalgesia, consistent with findings from our previous study 6 . Spirulina microalgae significantly reduced CCI-induced neuropathic pain.…”

“…Nisha Patro et al reported that oral use of Spirulina alleviates arthritis pain through suppressing inflammatory processes and microglial activation in the spinal cord 36 . Previously, we reported that inflammatory mediator release due to CCI is one of the main mechanisms leading to neuropathic pain 6 . Consistent with the studies which suggest an anti inflammatory property for Spirulina and its content Cphycocyanin 17,37,38 , it is possible that in the present study Spirulina led to analgesia through suppressing inflammatory mediators.…”

“…In our study, MDA as an oxidative stress marker did not change between control and treatment groups. Several in vitro and in vivo studies revealed the antioxidant properties of Spirulina through decrease of MDA levels 6,27,39 . However, the present results are consistent with our previous results 6 ; MDA levels were not significantly different between the control and neuropathy groups.…”

“…Several complicated and similar mechanisms have been associated with peripheral and central neuropathic pain. These mechanisms include increased release of excitatory neurotransmitters, modulation of descending inhibitory pathways, inflammatory reactions and oxidative stress [5][6][7] , all of which may change with time thereby increasing complications 8 . With regard to these complications, all of the approaches presented above have not shown sufficient evidence of effective neuropathic pain treatment 3,9 .…”

“…In light of these effects, it seems that the protective effects of Spirulina are, at least, due to its antioxidant properties, although other mechanisms may also play a role. Given the aforementioned impact of the role of oxidative stress and inflammation in peripheral neuropathic pain 6 , and the antioxidative properties of Spirulina microalgae, the aim of this study was to evaluate whether orally administered Spirulina could suppress neuropathic pain induced by chronic constriction injury (CCI) in rats. To our understanding, no other study has examined the effects of Spirulina therapy on CCI-induced neuropathic pain thus far.…”