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Mrgprd enhances excitability in specific populations of cutaneous murine polymodal nociceptors.

The Mas-related G protein-coupled receptor D (Mrgprd) is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologically relevant somatosensory stimuli that activate Mrgprd-expressing (Mrgprd(+)) neurons are currently unknown. To address these issues, we studied three Mrgprd knock-in mouse lines using an ex vivo somatosensory preparation to examine the role of the Mrgprd receptor and Mrgprd(+) afferents in cutaneous somatosensation. In mouse hairy skin, Mrgprd, as marked by expression of green fluorescent protein reporters, was expressed predominantly in the population of nonpeptidergic, TRPV1-negative, C-polymodal nociceptors. In mice lacking Mrgprd, this population of nociceptors exhibited decreased sensitivity to cold, heat, and mechanical stimuli. Additionally, in vitro patch-clamp studies were performed on cultured dorsal root ganglion neurons from Mrgprd(-/-) and Mrgprd(+/-) mice. These studies revealed a higher rheobase in neurons from Mrgprd(-/-) mice than from Mrgprd(+/-) mice. Furthermore, the application of the Mrgprd ligand beta-alanine significantly reduced the rheobase and increased the firing rate in neurons from Mrgprd(+/-) mice but was without effect in neurons from Mrgprd(-/-) mice. Our results demonstrate that Mrgprd influences the excitability of polymodal nonpeptidergic nociceptors to mechanical and thermal stimuli.

Pubmed ID: 19571152

Authors

  • Rau KK
  • McIlwrath SL
  • Wang H
  • Lawson JJ
  • Jankowski MP
  • Zylka MJ
  • Anderson DJ
  • Koerber HR

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

July 1, 2009

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS052848
  • Agency: NINDS NIH HHS, Id: P01 NS048499-05
  • Agency: NINDS NIH HHS, Id: R01 NS023725
  • Agency: NINDS NIH HHS, Id: R01 NS023725-20
  • Agency: NINDS NIH HHS, Id: R01 NS023725-21
  • Agency: NINDS NIH HHS, Id: R01 NS052848
  • Agency: NINDS NIH HHS, Id: R01 NS052848-03
  • Agency: NINDS NIH HHS, Id: R01 NS052848-04
  • Agency: NINDS NIH HHS, Id: R01 NS060725
  • Agency: NINDS NIH HHS, Id: R01 NS060725
  • Agency: NINDS NIH HHS, Id: R01 NS060725-01
  • Agency: NINDS NIH HHS, Id: R01 NS060725-02
  • Agency: NINDS NIH HHS, Id: R01 NS060725-03
  • Agency: NINDS NIH HHS, Id: R01 NS060725-04
  • Agency: NINDS NIH HHS, Id: R01 NS23275
  • Agency: NINDS NIH HHS, Id: R56 NS023725
  • Agency: NINDS NIH HHS, Id: R56 NS023725-22
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Analysis of Variance
  • Animals
  • Biophysics
  • Biotin
  • Calcitonin Gene-Related Peptide
  • Ganglia, Spinal
  • Green Fluorescent Proteins
  • In Vitro Techniques
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nociceptors
  • Patch-Clamp Techniques
  • Peripheral Nerves
  • Physical Stimulation
  • Receptors, G-Protein-Coupled
  • Sensory Thresholds
  • Skin
  • Spinal Cord
  • TRPV Cation Channels
  • beta-Alanine