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

http://www.ncbi.nlm.nih.gov/pubmed/19571152

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 RIS Download

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

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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:

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