title: The differential influences of melanocortins on nociception in the formalin and tail flick tests.
abstract: Melanocortins exert multiple physiological effects that include the modulation of immune responses, inflammation processes, and pain transmission. In the present study we investigated the peripheral activity of natural melanocortins - alpha-, beta-, gamma1- and gamma2-melanocyte stimulating hormone (MSH) - and melanocortin receptor subtypes 3 and 4 (MC3/4 receptor) antagonist HS014 in pain (formalin and tail flick) tests after peptide subcutaneous administration in mice. In the formalin test, among all substances tested only alpha-MSH (1 micromol/kg) statistically significantly inhibited the formalin-induced first phase pain response, however, all tested peptides (except gamma1-MSH) at the dose of 1 micromol/kg produced a pronounced inhibitory effect on nociceptive behavior in the second phase and this activity was comparable with that of indomethacin (reference drug, 5 mg/kg intraperitoneally); beta-MSH was also active at a dose 0.1 micromol/kg. In the tail flick test, alpha-MSH (1 micromol/kg) showed algesic, whereas HS014 (0.5 micromol/kg) and indomethacin (10 mg/kg) exerted analgesic activity. Other peptides did not exert any activity in the tail flick test. These data indicate that peripherally administered melanocortin receptor agonists alpha-MSH, beta-MSH and gamma2-MSH, as well as MC3/4 receptor antagonist HS014 induced antinociception on pain/inflammatory events caused by formalin suggesting a predominant anti-inflammatory role of these peptides.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles St. 21, Riga, LV-1006, Latvia. liga@biomed.lu.lv
authors.forename: Liga
authors.initials: L
authors.lastname: Zvejniece
authors.forename: Ruta
authors.initials: R
authors.lastname: Muceniece
authors.forename: Liga
authors.initials: L
authors.lastname: Krigere
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
authors.forename: Vija Z
authors.initials: VZ
authors.lastname: Klusa
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D008297:Male; D053486:Melanocortins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000502:physiology; D010147:Pain Measurement; D010456:Peptides, Cyclic / Q000494:pharmacology; D044101:Receptors, Melanocortin / Q000502:physiology; D000521:alpha-MSH / Q000494:pharmacology; D019824:beta-MSH; D019825:gamma-MSH / Q000494:pharmacology
chemical_list: D000700:Analgesics; C116941:HS014 cyclic peptide; D053486:Melanocortins; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; D019824:beta-MSH; D019825:gamma-MSH; D009569:Nitric Oxide; D000521:alpha-MSH