Melanocortin 4 receptor is expressed in the dorsal root ganglions and down-regulated in neuropathic rats

Recent reports have demonstrated effectiveness of melanocortin antagonists as potent analgesics, and have suggested that the spinal melanocortin 4 receptor (MC4-R) mediates their effects on pain transmission. These findings prompted us to investigate the changes in MC4-R mRNA level in the spinal cord and dorsal root ganglia (DRG) of neuropathic animals at different time points after sciatic nerve injury by quantitative real-time PCR. The spinal MC4-R mRNA level was not affected by sciatic nerve injury. In contrast, down-regulation of MC4-R mRNA in DRG developed 2 weeks after the injury and was parallel with the attenuated effectiveness of MC4-R ligands in neuropathic animals. The MC4-R adaptation in DRG observed in neuropathic rats indicates their important role in presynaptic modulation of activity of the primary afferents in neuropathic pain. (C) 2003 Elsevier Ireland Ltd. All rights reserved.