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Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways

Item Type:Article
Title:Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways
Creators Name:Simonetti, M. and Agarwal, N. and Stoesser, S. and Bali, K.K. and Karaulanov, E. and Kamble, R. and Pospisilova, B. and Kurejova, M. and Birchmeier, W. and Niehrs, C. and Heppenstall, P. and Kuner, R.
Abstract:Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we report that Wnt signaling pathways persist in adult sensory neurons and play a functional role in their sensitization in a pathophysiological context. We observed that Wnt3a recruits the Wnt-calcium signaling pathway and the Wnt planar cell polarity pathway in peripheral nerves to alter pain sensitivity in a modality-specific manner and we elucidated underlying mechanisms. In contrast, biochemical, pharmacological, and genetic studies revealed lack of functional relevance for the classical canonical {beta}-catenin pathway in peripheral sensory neurons in acute modulation of nociception. Finally, this study provides proof-of-concept for a translational potential for Wnt3a-Frizzled3 signaling in alleviating disease-related pain hypersensitivity in cancer-associated pain in vivo.
Keywords:Cultured Cells, Frizzled Receptors, HEK293 Cells, Hyperalgesia, Peripheral Nerves, Sensory Receptor Cells, Spinal Ganglia, Wnt Signaling Pathway, Wnt3A Protein, Animals, Mice
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press (U.S.A.)
Volume:83
Number:1
Page Range:104-121
Date:2 July 2014
Official Publication:https://doi.org/10.1016/j.neuron.2014.05.037
PubMed:View item in PubMed

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