Nociceptive tuning by stem cell factor/c-Kit signaling

Item Type:	Article
Title:	Nociceptive tuning by stem cell factor/c-Kit signaling
Creators Name:	Milenkovic, N. and Frahm, C. and Gassmann, M. and Griffel, C. and Erdmann, B. and Birchmeier, C. and Lewin, G.R. and Garratt, A.N.
Abstract:	The molecular mechanisms regulating the sensitivity of sensory circuits to environmental stimuli are poorly understood. We demonstrate here a central role for stem cell factor (SCF) and its receptor, c-Kit, in tuning the responsiveness of sensory neurons to natural stimuli. Mice lacking SCF/c-Kit signaling displayed profound thermal hypoalgesia, attributable to a marked elevation in the thermal threshold and reduction in spiking rate of heat-sensitive nociceptors. Acute activation of c-Kit by its ligand, SCF, resulted in a reduced thermal threshold and potentiation of heat-activated currents in isolated small-diameter neurons and thermal hyperalgesia in mice. SCF-induced thermal hyperalgesia required the TRP family cation channel TRPV1. Lack of c-Kit signaling during development resulted in hypersensitivity of discrete mechanoreceptive neuronal subtypes. Thus, c-Kit can now be grouped with a small family of receptor tyrosine kinases, including c-Ret and TrkA, that control the transduction properties of sensory neurons.
Keywords:	Molneuro, Sysbio, Signaling, Animals, Mice
Source:	Neuron
ISSN:	0896-6273
Publisher:	Cell Press
Volume:	56
Number:	5
Page Range:	893-906
Date:	6 December 2007
Official Publication:	https://doi.org/10.1016/j.neuron.2007.10.040
PubMed:	View item in PubMed

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