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Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of pa...

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Autores principales: Cobos, Enrique J., Nickerson, Chelsea A., Gao, Fuying, Chandran, Vijayendran, Bravo-Caparrós, Inmaculada, González-Cano, Rafael, Riva, Priscilla, Andrews, Nick A., Latremoliere, Alban, Seehus, Corey R., Perazzoli, Gloria, Nieto, Francisco R., Joller, Nicole, Painter, Michio W., Ma, Chi Him Eddie, Omura, Takao, Chesler, Elissa J., Geschwind, Daniel H., Coppola, Giovanni, Rangachari, Manu, Woolf, Clifford J., Costigan, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908229/
https://www.ncbi.nlm.nih.gov/pubmed/29386116
http://dx.doi.org/10.1016/j.celrep.2018.01.006
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author Cobos, Enrique J.
Nickerson, Chelsea A.
Gao, Fuying
Chandran, Vijayendran
Bravo-Caparrós, Inmaculada
González-Cano, Rafael
Riva, Priscilla
Andrews, Nick A.
Latremoliere, Alban
Seehus, Corey R.
Perazzoli, Gloria
Nieto, Francisco R.
Joller, Nicole
Painter, Michio W.
Ma, Chi Him Eddie
Omura, Takao
Chesler, Elissa J.
Geschwind, Daniel H.
Coppola, Giovanni
Rangachari, Manu
Woolf, Clifford J.
Costigan, Michael
author_facet Cobos, Enrique J.
Nickerson, Chelsea A.
Gao, Fuying
Chandran, Vijayendran
Bravo-Caparrós, Inmaculada
González-Cano, Rafael
Riva, Priscilla
Andrews, Nick A.
Latremoliere, Alban
Seehus, Corey R.
Perazzoli, Gloria
Nieto, Francisco R.
Joller, Nicole
Painter, Michio W.
Ma, Chi Him Eddie
Omura, Takao
Chesler, Elissa J.
Geschwind, Daniel H.
Coppola, Giovanni
Rangachari, Manu
Woolf, Clifford J.
Costigan, Michael
author_sort Cobos, Enrique J.
collection PubMed
description Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.
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spelling pubmed-59082292018-04-19 Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling Cobos, Enrique J. Nickerson, Chelsea A. Gao, Fuying Chandran, Vijayendran Bravo-Caparrós, Inmaculada González-Cano, Rafael Riva, Priscilla Andrews, Nick A. Latremoliere, Alban Seehus, Corey R. Perazzoli, Gloria Nieto, Francisco R. Joller, Nicole Painter, Michio W. Ma, Chi Him Eddie Omura, Takao Chesler, Elissa J. Geschwind, Daniel H. Coppola, Giovanni Rangachari, Manu Woolf, Clifford J. Costigan, Michael Cell Rep Article Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type. 2018-01-30 /pmc/articles/PMC5908229/ /pubmed/29386116 http://dx.doi.org/10.1016/j.celrep.2018.01.006 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Cobos, Enrique J.
Nickerson, Chelsea A.
Gao, Fuying
Chandran, Vijayendran
Bravo-Caparrós, Inmaculada
González-Cano, Rafael
Riva, Priscilla
Andrews, Nick A.
Latremoliere, Alban
Seehus, Corey R.
Perazzoli, Gloria
Nieto, Francisco R.
Joller, Nicole
Painter, Michio W.
Ma, Chi Him Eddie
Omura, Takao
Chesler, Elissa J.
Geschwind, Daniel H.
Coppola, Giovanni
Rangachari, Manu
Woolf, Clifford J.
Costigan, Michael
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title_full Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title_fullStr Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title_full_unstemmed Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title_short Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
title_sort mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908229/
https://www.ncbi.nlm.nih.gov/pubmed/29386116
http://dx.doi.org/10.1016/j.celrep.2018.01.006
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