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.