title: 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.affiliation: Faculty of Pharmaceutical Sciences, UCSI University, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Lee
authors.initials: L
authors.lastname: Ming-Tatt
authors.forename: Shaik Ibrahim
authors.initials: SI
authors.lastname: Khalivulla
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.forename: Nordin
authors.initials: N
authors.lastname: Lajis
authors.forename: Enoch Kumar
authors.initials: EK
authors.lastname: Perimal
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akira
authors.forename: Daud Israf
authors.initials: DI
authors.lastname: Ali
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry / Q000627:therapeutic use*; D003512:Cyclohexanones / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D001597:Benzylidene Compounds; D003512:Cyclohexanones; D054086:KATP Channels; D017473:Receptors, Opioid, kappa; C036468:cyclohexanone
keywords: ATP-sensitive potassium channel; Chronic constriction injury; Cyclic guanosine monophosphate; Neuropathic pain; Nitric oxide; Opioid receptor