Effect of mito-TEMPO, a mitochondria-targeted antioxidant, in rats with neuropathic pain

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Abstract

The therapeutic effects of mitochondria-targeted antioxidants have been demonstrated in many pathological conditions, but their effect on neuropathic pain remains unclear. The objective was to study the therapeutic effects and mechanisms of mito-TEMPO (MT), as a nitroxide conjugated with a triphenylphosphonium moiety, on neuropathic pain in rats. Rats were randomly assigned to sham control (sham), chronic constrictive injury (CCI) or MT treatment groups (sham+MT and CCI+MT). All animals received CCI of the left sciatic nerve except those in the sham group. Overall, 0.7 mg/kg of MT was intraperitoneally injected once daily for 14 consecutive days starting from day 7 after surgery. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were detected to assess pain behavior. Malondialdehyde and reduced glutathione content and total superoxide dismutase activity of serum and spinal cord tissues were estimated to assess oxidative stress levels. Mitochondrial morphology and dynamin-related proteins were used to evaluate mitochondrial function, such as fusion [Mitofusin (Mfn) and optic atrophy 1 gene protein (OPA1)] and fission [dynamin-related protein (DRP1) and Fis1]. Paw withdrawal threshold and thermal paw withdrawal latency were significantly increased in the CCI+MT group compared with the CCI group. The malondialdehyde content was decreased whereas glutathione content and superoxide dismutase activity were increased in the serum of CCI+MT rats. Furthermore, MT substantially attenuated the elevated number and decreased size of mitochondria induced by CCI. Finally, MT significantly increased expressions of Mfn1 and OPA1 and significantly decreased expression of DRP1 and Fis1. The mitochondria-targeted antioxidant MT relieved neuropathic pain induced by CCI by protecting mitochondria against oxidative stress injury.

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