The absence of sensory axon bifurcation affects nociception and termination fields of afferents in the spinal cord

  • A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.

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Author:Philip Tröster, Julia Haseleu, Jonas Petersen, Oliver Drees, Achim SchmidtkoORCiDGND, Frederick Schwaller, Gary R. Lewin, Gohar Ter-Avetisyan, York Winter, Stefanie Peters, Susanne Feil, Robert Feil, Fritz G. Rathjen, Hannes Schmidt
URN:urn:nbn:de:hebis:30:3-458712
DOI:https://doi.org/10.3389/fnmol.2018.00019
ISSN:1662-5099
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29472841
Parent Title (English):Frontiers in molecular neuroscience
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Contributor(s):Simone Di Giovanni
Document Type:Article
Language:English
Year of Completion:2018
Year of first Publication:2018
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/13
Tag:Npr2; axon bifurcation; axonal pathfinding; cGKI; development; nociception and pain; sensory neurons
Volume:11
Issue:Art. 19
Page Number:18
First Page:1
Last Page:18
Note:
Copyright © 2018 Tröster, Haseleu, Petersen, Drees, Schmidtko, Schwaller, Lewin, Ter-Avetisyan, Winter, Peters, Feil, Feil, Rathjen and Schmidt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS-PPN:431527814
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0