Potential use of melatonergic drugs in analgesia : mechanisms of action

• Autores: Srinivasan, Venkataramanujan; Pandi Perumal, Seithikurippu R.; Moscovitch, Adam; Spence, David Warren; Trakht, Ilya; Brown, Gregory M.; Cardinali, Daniel Pedro
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Brain Research Bulletin. 2010;81
• Materia: ANALGESIA; MELATONINA; RECEPTORES DE MELATONINA; NOCICEPTORES; RECEPTORES DE OPIOIDES
• Institución: Pontificia Universidad Católica Argentina

Fil: Srinivasan, Venkataramanujan. Sri Sathya Sai Medical Educational and Research Foundation; India
Fil: Pandi Perumal, Seithikurippu R. Somnogen Inc.; Estados Unidos
Fil: Moscovitch, Adam. Investigador Independiente; Canadá
Fil: Spence, David Warren. Investigador Independiente; Canadá
Fil: Trakht, Ilya. Universidad Columbia. Colegio de Médicos y Cirujanos. Departamento de Medicina. División de Farmacología Clínica y Terapéutica Experimental; Estados Unidos
Fil: Brown, Gregory M. Universidad de Toronto. Departamento de Psiquiatría; Canadá
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
abstract: Melatonin is a remarkable molecule with diverse physiological functions. Some of its effects are mediated by receptors while other, like cytoprotection, seem to depend on direct and indirect scavenging of free radicals not involving receptors. Among melatonin´s many effects, its antinociceptive actions have attracted attention. When given orally, intraperitoneally, locally, intrathecally or through intracerebroventricular routes, melatonin exerts antinociceptive and antiallodynic actions in a variety of animal models. These effects have been demonstrated in animal models of acute pain like the tail-flick test, formalin test or endotoxin-induced hyperalgesia as well as in models of neuropathic pain like nerve ligation. Glutamate, gamma-aminobutyric acid, and particularly, opioid neurotransmission have been demonstrated to be involved in melatonin´s analgesia. Results using melatonin receptor antagonists support the participation of melatonin receptors in melatonin´s analgesia. However, discrepancies between the affinity of the receptors and the very high doses of melatonin needed to cause effects in vivo raise doubts about the uniqueness of that physiopathological interpretation. Indeed, melatonin could play a role in pain through several alternative mechanisms including free radicals scavenging or nitric oxide synthase inhibition. The use of melatonin analogs like the MT1/MT2 agonist ramelteon, which lacks free radical scavenging activity, could be useful to unravel the mechanism of action of melatonin in analgesia. Melatonin has a promising role as an analgesic drug that could be used for alleviating pain associated with cancer, headache or surgical procedures.