Zerumbone Alleviates Neuropathic Pain through the Involvement of L-Arginine-Nitric Oxide-cGMP-K+ ATP Channel Pathways in Chronic Constriction Injury in Mice Model

Abstract

The present study investigates the involvement of the L-Arginine-Nitric Oxide-cGMP-K+ ATP pathways responsible for the action of anti-Allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of L-Arginine-NO-cGMP-K+ was assessed by the von Frey and the Randall-Selitto tests. Both allodynia and hyperalgesia assessments were carried out on the 14th day post CCI, 30 min after treatments were given for each respective pathway. Anti-Allodynic and antihyperalgesic effects of zerumbone (10 mg/kg, i.p) were significantly reversed by the pre-Treatment of L-Arginine (10 mg/kg), 1H [1,2,4]Oxadiazole[4,3a]quinoxalin-1-one (ODQ), a soluble guanosyl cyclase blocker (2 mg/kg i.p.) and glibenclamide (ATP-sensitive potassium channel blocker) (10 mg/kg i.p.) (p < 0.05). Taken together, these results indicate that systemic administration of zerumbone produces significant anti-Allodynic and antihyperalgesic activities in neuropathic pain in mice possibly due to involvement of the L-Arginine-NO-cGMP-PKG-K+ ATP channel pathways in CCI model.