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 proc...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00019/full |
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| author | Philip Tröster Julia Haseleu Jonas Petersen Jonas Petersen Oliver Drees Achim Schmidtko Achim Schmidtko Frederick Schwaller Gary R. Lewin Gohar Ter-Avetisyan York Winter Stefanie Peters Susanne Feil Robert Feil Fritz G. Rathjen Hannes Schmidt |
| author_facet | Philip Tröster Julia Haseleu Jonas Petersen Jonas Petersen Oliver Drees Achim Schmidtko Achim Schmidtko Frederick Schwaller Gary R. Lewin Gohar Ter-Avetisyan York Winter Stefanie Peters Susanne Feil Robert Feil Fritz G. Rathjen Hannes Schmidt |
| author_sort | Philip Tröster |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:47:57Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T01:47:57Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-27326bdcde95470aba32eea6fe3c906d2022-12-22T03:53:00ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00019318709The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal CordPhilip Tröster0Julia Haseleu1Jonas Petersen2Jonas Petersen3Oliver Drees4Achim Schmidtko5Achim Schmidtko6Frederick Schwaller7Gary R. Lewin8Gohar Ter-Avetisyan9York Winter10Stefanie Peters11Susanne Feil12Robert Feil13Fritz G. Rathjen14Hannes Schmidt15Developmental Neurobiology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyMolecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyInstitute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, GermanyInstitute of Pharmacology and Toxicology, Zentrum für Biomedizinische Ausbildung und Forschung (ZBAF), Witten/Herdecke University, Witten, GermanyInstitute of Pharmacology and Toxicology, Zentrum für Biomedizinische Ausbildung und Forschung (ZBAF), Witten/Herdecke University, Witten, GermanyInstitute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, GermanyInstitute of Pharmacology and Toxicology, Zentrum für Biomedizinische Ausbildung und Forschung (ZBAF), Witten/Herdecke University, Witten, GermanyMolecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyMolecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyDevelopmental Neurobiology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyCognitive Neurobiology, Humboldt University of Berlin, Berlin, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, GermanyDevelopmental Neurobiology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyDevelopmental Neurobiology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyA 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.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00019/fullsensory neuronsaxon bifurcationNpr2cGKIdevelopmentnociception and pain |
| spellingShingle | Philip Tröster Julia Haseleu Jonas Petersen Jonas Petersen Oliver Drees Achim Schmidtko Achim Schmidtko Frederick Schwaller Gary R. Lewin Gohar Ter-Avetisyan York Winter Stefanie Peters Susanne Feil Robert Feil Fritz G. Rathjen Hannes Schmidt The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord Frontiers in Molecular Neuroscience sensory neurons axon bifurcation Npr2 cGKI development nociception and pain |
| title | The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord |
| title_full | The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord |
| title_fullStr | The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord |
| title_full_unstemmed | The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord |
| title_short | The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord |
| title_sort | absence of sensory axon bifurcation affects nociception and termination fields of afferents in the spinal cord |
| topic | sensory neurons axon bifurcation Npr2 cGKI development nociception and pain |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00019/full |
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