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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13952

Milenkovic, N; Frahm, C; Gassmann, M; Griffel, C; Erdmann, B; Birchmeier, C; Lewin, G R; Garratt, A N (2007). Nociceptive tuning by stem cell factor/c-Kit signaling. Neuron, 56(5):893-906.

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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.

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:06 December 2007
Deposited On:19 Mar 2009 16:43
Last Modified:27 Nov 2013 22:04
Publisher:Elsevier
ISSN:0896-6273
Publisher DOI:10.1016/j.neuron.2007.10.040
PubMed ID:18054864
Citations:Web of Science®. Times Cited: 19
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