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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.

The present study was conducted to investigate the potential of zerumbone, a bioactive sesquiterpene of Zingiber zerumbet (L) Smith (Z. zerumbet) in anti-allodynic and antihyperalgesic properties in neuropathic pain induced by chronic constriction injury (CCI) in mice. We used this model and demonstrated the comparison of different number of sciatic nerve ligation (1, 2, 3 and 4). The outcome revealed that a single ligation CCI animal model on the sciatic nerve is enough to mimic the symptoms of neuropathic pain such as hyperalgesia and allodynia with almost similar effect with the usual 4 ligations sciatic nerve in CCI animal model. Indeed, acute and repeated intraperitoneal (i.p) administration (on 14th day and continued administration once daily for 7 days) of zerumbone (10, 50, 100 mg/kg) significantly exhibited dose-dependent inhibition of chronic constriction injury induced-neuropathic pain in mice, when evaluated using von Frey filament test, cold plate, Randall-Selitto and Hargreaves plantar test (p<0.05). The compound was found to exert anti-allodynic and antihyperalgesic properties in chronic constriction injury (CCI) model and the optimum dose for zerumbone was found out to be 10 mg/kg. The anti-allodynic and antihyperalgesic effect of zerumbone (10 mg/kg i.p) were also significantly reversed by pre-treatment of L-arginine (10 mg/kg), 1H [1,2,4] Oxadiazole [4,3a] quinoxalin-1-one (ODQ), soluble guanosyl cyclase blocker (2 mg/kg i.p) and glibenclamide (ATPsensitive potassium channel blocker) (10 mg/kg i.p). In addition, the histology of nerve morphology also showed a profound attenuation of mast cells around nerve fibres after treated 7 days daily with 10 mg/kg i.p and 50 mg/kg i.p of zerumbone (p<0.05). Even though, zerumbone failed to produce significant result with vehicle-treated group on the swelling of nerve fibre but the anti-inflammatory effect of zerumbone was able to attenuate the inflammatory cells surrounding the nerve fibre. Together, these fi

Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1 mg/kgi.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis.