The differential influences of melanocortins on nociception in the formalin and tail flick tests.
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.
Zvejniece
Liga
L
Latvian Institute of Organic Synthesis, Aizkraukles St. 21, Riga, LV-1006, Latvia. liga@biomed.lu.lv
Muceniece
Ruta
R
Krigere
Liga
L
Dambrova
Maija
M
Klusa
Vija Z
VZ
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
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