title: Mechanisms involved in the antinociception caused by melatonin in mice.
abstract: The present study assesses the antinociceptive effect of melatonin in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. Melatonin administered by intraperitoneal (i.p., 10-100 mg/kg), intracerebroventricular (i.c.v., 250-500 pmol/site) and intraplantar (i.pl., 30-100 ng/i.pl.) routes, reduced in a dose-dependent manner the nociception caused by i.pl. injection of glutamate (10 micromol/paw), with mean ID50 values of 32.6 mg/kg, 200 pmol/site and 59 ng/i.pl., respectively. Furthermore, melatonin in the dose range of 10-100 mg/kg, i.p., reduced the neurogenic pain caused by i.pl. injection of capsaicin (5.2 nmol/paw) with inhibition of 48 +/- 4%. The antinociceptive effect of melatonin (100 mg/kg, i.p.) on glutamate-induced nociception was completely prevented by the pretreatment of animals with naloxone (a nonselective opioid receptor antagonist, 1 mg/kg, i.p.), ketanserin (a preferential 5-HT2A receptor antagonist, 1 mg/kg, i.p.), sulpiride (a D2 receptor antagonist, 50 mg/kg, i.p.), L-arginine (a precursor of nitric oxide, 600 mg/kg, i.p.), yohimbine (an alpha2-adrenoceptor antagonist, 0.15 mg/kg, i.p.) and luzindole (a preferential MT2 receptor antagonist, 10 mg/kg, i.p.), but was not affected by the pretreatment with D-arginine (an inactive isomer of L-arginine, 600 mg/kg, i.p.), prazosin (an alpha1-adrenoceptor antagonist, 0.15 mg/kg, i.p.) or after bilateral adrenalectomy. Collectively, present results suggest that melatonin produces peripheral and central antinociception when assessed on capsaicin- or glutamate-induced pain in mice through mechanisms that are likely mediated by interaction with plasma membrane-bound melatonin receptors and modulated by opioid, serotonergic (5-HT2A receptors), dopaminergic (D2-receptors), adrenergic (alpha2-adrenoceptors) systems as well as the L-arginine-nitric oxide pathway.
authors.affiliation: Departamentos de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis-SC, Brazil.
authors.forename: Michela
authors.initials: M
authors.lastname: Mantovani
authors.forename: Manuella P
authors.initials: MP
authors.lastname: Kaster
authors.forename: Roberto
authors.initials: R
authors.lastname: Pertile
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000315:Adrenalectomy; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D008550:Melatonin; D002211:Capsaicin