Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors (original) (raw)

2009, Journal of Neuroscience

The Mrgprd receptor is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologicallyrelevant somatosensory stimuli that activate Mrgprd-expressing (Mrgprd+) neurons are currently unknown. To address these issues, we studied three Mrgprd knockin 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 GFP reporters, was expressed predominantly in the population of non-peptidergic, 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 DRG neurons from Mrgprd−/− and Mrgprd+/− mice. These studies revealed a higher rheobase in neurons from Mrgprd−/− mice than from Mrgprd+/− mice. Furthermore, in vitro the application of the Mrgprd ligand β-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.

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