title: Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.
abstract: Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.
authors.affiliation: Department of Pharmacology and Toxicology, Otago School of Medical Sciences, University of Otago , Dunedin , New Zealand.
authors.forename: Oliver
authors.initials: O
authors.lastname: Linsell
authors.forename: Philip W
authors.initials: PW
authors.lastname: Brownjohn
authors.forename: Hayley
authors.initials: H
authors.lastname: Nehoff
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.forename: John C
authors.initials: JC
authors.lastname: Ashton
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D004195:Disease Models, Animal; D006207:Half-Life; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D008298:Maleates / Q000737:chemistry*; D008823:Micelles; D009025:Morpholines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy*; D011137:Polystyrenes / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D008298:Maleates; D008823:Micelles; D009025:Morpholines; D009281:Naphthalenes; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: 212-2; Cannabinoid; WIN 55; nanoparticle; neuropathic pain; rotarod; styrene maleic acid