Anti-hyperalgesic Effect of a Benzilidine-cyclohexanone Analogue on a Mouse Model of Chronic Constriction Injury-induced Neuropathic Pain: Participation of the κ-opioid Receptor and KATP

• Main Authors: Akhtar, Muhammad Nadeem, Shaik Ibrahim, Khalivulla, Lee, Ming-Tatt, Nordin, Lajis, Enoch Kumar, Perimal, Ahmad, Akira, Daud Israf, Ali, Mohd Roslan, Sulaiman
• Format: Article
• Language: English
• Published: Elsevier 2013
• Subjects: QR Microbiology
• Online Access: http://umpir.ump.edu.my/id/eprint/5245/1/fist-2013-nadeem-artAnti-HyperalgesicEffect.pdf; http://umpir.ump.edu.my/id/eprint/5245/; http://dx.doi.org/10.1016/j.pbb.2013.10.019

The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall–Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.