Analyzing the role of cannabinoids as modulators of Wnt/β-catenin signaling pathway for their use in the management of neuropathic pain

Abstract Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/ β -catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids ( 1 – 6 ) from the leaves of Cannabis sativa and an epoxy derivative of compound 2 , here upon referred to as 2a , on modulating Wnt/ β -catenin signaling pathway. The results presented in this study show that compound 1 , 2 and 2a exhibited potent inhibitory activity against Wnt/ β -catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2 , under similar conditions. Taken together, compound 1 , 2 and 2a , by virtue of their inhibition of Wnt /β -catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.