RESUMO
Substantial evidence has suggested that deep brain stimulation of the cuneiform nucleus has become a remarkable treatment option for intractable pain, but the possible mechanism is poorly understood. Using a melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) reporter knockin mouse, we showed that a large number of MC4R-GFP-positive neurons were expressed in the cuneiform nucleus. Immunofluorescence revealed that approximately 40%-50% of MC4R-GFP-positive neurons expressed mu opioid receptors, indicating that they were opioidergic signaling. Our findings support the hypothesis that MC4R expression in the cuneiform nucleus is involved in the modulation of opioidergic signaling.
Assuntos
Animais , Camundongos , Regulação da Expressão Gênica , Técnicas de Introdução de Genes , Genes Reporter , Proteínas de Fluorescência Verde , Genética , Metabolismo , Camundongos Transgênicos , Microtomia , Formação Reticular Mesencefálica , Biologia Celular , Metabolismo , Neurônios , Biologia Celular , Metabolismo , Receptor Tipo 4 de Melanocortina , Genética , Metabolismo , Receptores Opioides mu , Genética , Metabolismo , Proteínas Recombinantes de Fusão , Genética , Metabolismo , Transdução de SinaisRESUMO
The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
Assuntos
Animais , Feminino , Masculino , Camundongos , Bulbo , Biologia Celular , Metabolismo , Camundongos Transgênicos , Vias Neurais , Biologia Celular , Metabolismo , Neurônios Aferentes , Biologia Celular , Metabolismo , Nociceptividade , Fisiologia , Receptor Tipo 4 de Melanocortina , Genética , Metabolismo , Neurônios Serotoninérgicos , Metabolismo , Tirosina 3-Mono-Oxigenase , MetabolismoRESUMO
The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.