Melanocortin-4 Receptor Expression in the Cuneiform Nucleus Is Involved in Modulation of Opioidergic Signaling

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 MC4 R expression in the cuneiform nucleus is involved in the modulation of opioidergic signaling.