Idebenone attenuates sciatic nerve ligation-induced neuropathic pain through modulating antioxidant and...

Neuropathic pain is a complex clinical condition arising from damage to or dysfunction of the peripheral or central nervous system. This study aimed to investigate the therapeutic potential of idebenone, a compound with potent antioxidant and anti-inflammatory properties, in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve, and to elucidate its underlying mechanisms through biochemical, electrophysiological, and histopathological analyses.A total of 42 male Sprague-Dawley rats were randomly allocated into six groups: Sham, CCI, idebenone 50 mg/kg, idebenone 100 mg/kg, idebenone 200 mg/kg, and pregabalin (10 mg/kg). Following 14 days of treatment, thermal and mechanical hyperalgesia were assessed using the hot plate and paw withdrawal tests. Biochemical analyses included the determination of serum levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10), while electrophysiological, histopathological, and stereological evaluations were conducted to assess nerve tissue alterations.Idebenone treatment significantly attenuated both thermal and mechanical hyperalgesia induced by CCI. Moreover, idebenone increased GPx, SOD, and IL-10 levels, while reducing MDA and TNF-α levels. Electrophysiologically, idebenone enhanced compound muscle action potential amplitude without significantly affecting latency. Histopathological findings indicated that idebenone did not significantly alter the number of myelinated axons but was unable to prevent the CCI-induced reduction in myelinated axon area. Overall, idebenone exhibited antioxidant, anti-inflammatory, and neuroprotective effects, as evidenced by the modulation of oxidative stress markers, suppression of pro-inflammatory cytokines, enhancement of anti-inflammatory responses, and improvement in functional nerve parameters.These findings suggest that idebenone may represent a promising therapeutic candidate for neuropathic pain; however, further clinical studies are warranted to establish its efficacy and translational potential in human subjects.