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Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse.

Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4 (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200 (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.

Pubmed ID: 22592759


  • Gautron L
  • Lee CE
  • Lee S
  • Elmquist JK


The Journal of comparative neurology

Publication Data

December 1, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: P01 DK088761
  • Agency: NIDDK NIH HHS, Id: P01DK088761
  • Agency: NIDDK NIH HHS, Id: R01 DK053301
  • Agency: NIDDK NIH HHS, Id: R01 DK088423
  • Agency: NIDDK NIH HHS, Id: R01DK53301
  • Agency: NIDDK NIH HHS, Id: R37 DK053301
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185
  • Agency: NIDDK NIH HHS, Id: RL1DK081185

Mesh Terms

  • Animals
  • Ganglia, Spinal
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Neurons, Afferent
  • Receptor, Melanocortin, Type 4
  • Vagus Nerve