Mrgprd enhances excitability in specific populations of cutaneous murine polymodal nociceptors

KK Rau, SL McIlwrath, H Wang, JJ Lawson… - Journal of …, 2009 - Soc Neuroscience
KK Rau, SL McIlwrath, H Wang, JJ Lawson, MP Jankowski, MJ Zylka, DJ Anderson
Journal of Neuroscience, 2009Soc Neuroscience
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 …
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 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.
Soc Neuroscience