Potential use of melatonergic drugs in analgesia: Mechanisms of action

• Autores: Srinivasan, Venkataramanujam; Pandi Perumal, Seithikurippu R.; Spence, David Warren; Moscovitch, Adam; Trakht, Ilya; Brown, Gregory M.; Cardinali, Daniel Pedro
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ALLODYNIA; ANALGESIA; MELATONIN; MELATONIN ANALOGS; MELATONIN RECEPTORS; NEUROPATHIC PAIN; NOCICEPTION; OPIOID RECEPTORS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Srinivasan, Venkataramanujam. Shri Sathya Sai Medical College and Research Institute; India
Fil: Pandi Perumal, Seithikurippu R.. Somnogen; Estados Unidos
Fil: Spence, David Warren. Canadian Sleep Society; Canadá
Fil: Moscovitch, Adam. Canadian Sleep Society; Canadá
Fil: Trakht, Ilya. Columbia University College of Physicians and Surgeons; Estados Unidos
Fil: Brown, Gregory M.. University of Toronto; Canadá
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina