Octanol alleviates chronic constriction injury of sciatic nerve-induced peripheral neuropathy by regulating AKT/mTOR signaling.

Abstract

Activation of gap junction channels can induce neuropathic pain. Octanol can limit the conductance of gap junctions containing connexin 43 proteins. Thus, this study focused on the roles of octanol in chronic constriction injury (CCI)-induced peripheral neuropathy in mice and its mechanisms of action. Male mice were assigned into control, sham, CCI, CCI + Octanol-20mg/kg, CCI + Octanol-40mg/kg and CCI + Octanol-80mg/kg groups. CCI was performed by applying three loose ligations to mouse sciatic nerve, and the mice with CCI was administered with 20mg/kg, 40mg/kg, or 80mg/kg octanol. The neuropathic pain development was examined by assessing thermal withdrawal latency, paw withdrawal mechanical threshold, and sciatic functional index. Histopathological changes were evaluated by hematoxylin and eosin staining. The phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) was examined by western blotting. The expression of Akt and mTOR was also evaluated by immunofluorescence staining. Octanol alleviated the CCI-induced mechanical and thermal hyperalgesia and sciatic functional loss. Additionally, octanol relieved the CCI-induced abnormal histopathological changes. Mechanistically, octanol inactivated the Akt/mTOR pathway in the mice with CCI. In conclusion, octanol can alleviate CCI-induced peripheral neuropathic by regulating the Akt/mTOR pathway and might be a novel pharmacological intervention for neuropathic pain.