Irisin alleviates chronic constriction injury-induced hyperalgesia and affective disorders in mice through NF-κB and Nrf2 signaling pathways

This research is to explore the impacts of irisin on hyperalgesia and behavioral deficits caused by chronic constriction injury (CCI) and the underlying mechanisms. The CCI mice model was used in this study. The experimental mice were assigned into sham, sham + irisin (3 μg/kg), CCI, CCI + irisin (0.1, 1, and 3 μg/kg), and CCI + irisin (3 μg/kg) + ML385 (30 mg/kg) groups. The results showed that after CCI injury, the mice exhibited hyperalgesia, depression, and anxiety. In addition, the levels of inflammatory cytokines NF-κB, IL-1β, IL-6, TNF-α, and iNOS increased in the mice hippocampus, frontal cortex, and spinal cord. Moreover, oxidative stress relevant factor MDA increased, while GSH and SOD decreased in the mice hippocampus, frontal cortex, and spinal cord. However, irisin treatment ameliorated CCI-induced mechanical allodynia, thermal hyperalgesia, depressive, and anxiety behaviors, and reversed the abnormal expressions of inflammatory and oxidative stress relevant cytokines. Interestingly, these therapeutic effects of irisin were partly abolished by ML385, a specific Nrf2 antagonist. Taken together, irisin may be an effective therapeutic agent for CCI-induced neuralgia and the affective disorders, and the mechanisms may be associated with the anti-neuroinflammation mediated by NF-κB and the anti- oxidative stress function regulated by Nrf2.