title: Melanocortin receptor agonists and antagonists modulate nociceptive sensitivity in the mouse formalin test.
abstract: A number of studies suggest the involvement of melanocortins in nociception, and although the mechanism through which this occurs is still unknown, experimental evidence would suggest an involvement of melanocortin MC(4) receptors. We investigated the effect of melanocortin receptor agonist and antagonists on nociceptive behaviour induced by formalin in the mouse. The intrathecal injection of the melanocortin receptor agonist MTII ([Ac-Nle(4),Asp(5),D-Phe(7),Lys(10)]cyclo-alpha-MSH-(4-10) amide) (5 nmol; P<0.05) significantly increased nociception in both phases of the formalin test, whereas the synthetic melanocortin receptor antagonists, SHU9119 ([Ac-Nle(4),Asp(5),D-2-Nal(7),Lys(10)]cyclo-alpha-MSH-(4-10) amide) (5 nmol), HS014 ([Ac-Cys(11),D-2-Nal(14),Cys(18)]beta-MSH-(11-22)amide) (5 nmol), and JKC-363 (cyclic [Mpr(11),D-Nal(14),Cys(18),Asp(22)-NH(2)]beta-MSH-11-22)) (5 nmol), and the endogenous receptor antagonist Agouti-related protein (AgRP) (1.5 nmol) were effective in reducing nociception in the late phase of the formalin test (50-60% of reduction in licking/flinching response; P<0.05). The present findings further support the involvement of the melanocortin system in the control of nociception. Moreover, considering that melanocortin MC(4) receptors are the only melanocortin subtype receptors present in the spinal cord, we can assume that the activity of the peptides in the formalin model is mediated through melanocortin MC(4) receptors.
authors.affiliation: Schering-Plough Research Institute, San Raffaele Science Park, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bellasio
authors.forename: Elisa
authors.initials: E
authors.lastname: Nicolussi
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010456:Peptides, Cyclic / Q000494:pharmacology; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D000521:alpha-MSH / Q000031:analogs & derivatives
chemical_list: C116941:HS014 cyclic peptide; D009842:Oligopeptides; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones