Potential use of melatonergic drugs in analgesia: Mechanisms of action

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...

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Detalles Bibliográficos
Autores: Srinivasan, Venkataramanujam, Pandi Perumal, Seithikurippu R., Spence, David Warren, Moscovitch, Adam, Trakht, Ilya, Brown, Gregory M., Cardinali, Daniel Pedro
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/98829
Acceso en línea:http://hdl.handle.net/11336/98829
Access Level:acceso abierto
Palabra clave:ALLODYNIA
ANALGESIA
MELATONIN
MELATONIN ANALOGS
MELATONIN RECEPTORS
NEUROPATHIC PAIN
NOCICEPTION
OPIOID RECEPTORS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario: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.