title: Antihyperalgesic effect of [(±)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl]methanol: participation of the NO/cGMP/KATP pathway and κ-opioid receptor.
abstract: The present study used behavioral analyses to investigate the involvement of the NO/cGMP/KATP pathway, serotoninergic, and opioid systems in the antinociceptive action of [(±)-(2,4,6-cis)-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl]methanol (CTHP) in mice. Oral administration of CTHP (1, 5, 10, and 30 mg/kg) exerted effects at higher doses in chemical models of nociception (the acetic acid writhing and formalin tests) as well as a thermal model (the tail-flick test). It was also found that pretreatment with L-N-nitroarginine methyl ester (nonselective nitric oxide synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (selective inhibitor of nitric oxide-sensitive guanosyl cyclase), glibenclamide (selective ATP-sensitive K channel blocker), naloxone (nonselective opioid receptor blocker), and nor-binaltorphimine (selective κ-opioid receptor blocker), but not methylnaltrexone (peripheral μ-opioid receptor blocker) or naltrindole (selective δ-opioid receptor blocker), reversed the antinociceptive effect of CTHP. In addition, CTHP induced the development of tolerance in the tail-flick test: the tolerance appeared later compared with morphine, and was only observed with a higher dose. Taken together, the present study showed that the systemic administration of CTHP reduced pain induced by chemical and thermal stimuli. We also suggest that the possible mechanisms include the involvement of the NO/cGMP/KATP pathway and the κ-opioid receptor.
authors.affiliation: aPostgraduate Program in Physiological Sciences, Institute of Biological Sciences and Health, Federal Rural University of Rio de Janeiro bPharmacology Laboratory, Department of Physiological Sciences, Institute of Biological Sciences and Health, Federal Rural University of Rio de Janeiro, Seropédica, RJ cFederal Institute of Education, Science and Technology of Bahia, Campus Catu, Barão de Camaçari, Catu, BA dOrganic Medicinal Synthesis Laboratory of Paraiba, Department of Chemistry, Federal University of Paraíba, Campus I, João Pessoa, PB, Brazil.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Gonçalves
authors.forename: Saulo L
authors.initials: SL
authors.lastname: Capim
authors.forename: Mário L A A
authors.initials: ML
authors.lastname: Vasconcellos
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Marinho
mesh_terms: D019342:Acetic Acid / Q000008:administration & dosage; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010147:Pain Measurement; D011714:Pyrans / Q000008:administration & dosage / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*
chemical_list: C000624575:4-chloro-6-(naphthalen-1-yl)tetrahydro-2H-pyran-2-yl)methanol; D000700:Analgesics; D054086:KATP Channels; D009281:Naphthalenes; D011714:Pyrans; D017473:Receptors, Opioid, kappa; D009569:Nitric Oxide; D009020:Morphine; D006152:Cyclic GMP; D019342:Acetic Acid