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.
Starowicz
Katarzyna
K
Institute of Pharmacology, Polish Academy of Sciences, Department of Molecular Neuropharmacology, 12 Smetna Street, 31-343 Cracow, Poland.
Bilecki
Wiktor
W
Sieja
Agnieszka
A
Przewlocka
Barbara
B
Przewlocki
Ryszard
R
D000818:Animals; D015536:Down-Regulation / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000378:metabolism*; D017288:Pain Threshold / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000096:biosynthesis*; D020426:Sciatic Neuropathy / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
C470072:MC4R protein, human; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4