TY  - JOUR
A1  - Tröster, Philip
A1  - Haseleu, Julia
A1  - Petersen, Jonas
A1  - Drees, Oliver
A1  - Schmidtko, Achim
A1  - Schwaller, Frederick
A1  - Lewin, Gary R.
A1  - Ter-Avetisyan, Gohar
A1  - Winter, York
A1  - Peters, Stefanie
A1  - Feil, Susanne
A1  - Feil, Robert
A1  - Rathjen, Fritz G.
A1  - Schmidt, Hannes
T1  - The absence of sensory axon bifurcation affects nociception and termination fields of afferents in the spinal cord
T2  - Frontiers in molecular neuroscience
N2  - 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.
KW  - sensory neurons
KW  - axon bifurcation
KW  - Npr2
KW  - cGKI
KW  - development
KW  - nociception and pain
KW  - axonal pathfinding
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45871
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458712
SN  - 1662-5099
N1  - 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.
VL  - 11
IS  - Art. 19
SP  - 1
EP  - 18
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -