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.

Abstract

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 1.0mg/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.

• Authors: Lee Ming-Tatt, Shaik Ibrahim Khalivulla, Muhammad Nadeem Akhtar, Nordin Lajis, Enoch Kumar Perimal, Ahmad Akira, Daud Israf Ali, Mohd Roslan Sulaiman
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 114-115 Pg. 58-63 (Dec 2013) ISSN: 1873-5177 [Electronic] United States
• PMID: 24201054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Benzylidene Compounds
• Cyclohexanones
• KATP Channels
• Receptors, Opioid, kappa
• cyclohexanone

Topics

• Animals
• Benzylidene Compounds (chemistry, therapeutic use)
• Cyclohexanones (chemistry, therapeutic use)
• Disease Models, Animal
• KATP Channels (physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Neuralgia (drug therapy, etiology)
• Receptors, Opioid, kappa (physiology)
• Signal Transduction