[PDF][PDF] Nociceptive tuning by stem cell factor/c-Kit signaling

N Milenkovic, C Frahm, M Gassmann, C Griffel… - Neuron, 2007 - cell.com
N Milenkovic, C Frahm, M Gassmann, C Griffel, B Erdmann, C Birchmeier, GR Lewin
Neuron, 2007cell.com
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 …
Summary
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.
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