Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons

Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which Trk...

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Autores: Dhandapani, Rahul, Arokiaraj, Cynthia Mary, Taberner, Francisco J, Pacifico, Paola, Raja, Sruthi, Nocchi, Linda, Portulano, Carla, Franciosa, Federica, Maffei, Mariano, Hussain, Ahmad Fawzi, de Castro Reis, Fernanda, REYMOND, Luc, Perlas, Emerald, GARCOVICH, Simone, Barth, Stefan
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/38892
Acceso en línea:https://hdl.handle.net/11000/38892
Access Level:acceso abierto
Palabra clave:mechanical allodynia
neuropathic pain
TrkB-Cre-expressing neurons
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spelling Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neuronsDhandapani, RahulArokiaraj, Cynthia MaryTaberner, Francisco JPacifico, Paola Raja, SruthiNocchi, LindaPortulano, CarlaFranciosa, Federica Maffei, MarianoHussain, Ahmad Fawzide Castro Reis, FernandaREYMOND, LucPerlas, EmeraldGARCOVICH, SimoneBarth, Stefanmechanical allodynianeuropathic painTrkB-Cre-expressing neuronsMechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment.PMCInstitutos de la UMH::Instituto de Neurociencias202620262018info:eu-repo/semantics/articleapplication/pdf14application/pdfhttps://hdl.handle.net/11000/38892reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheInglés10.1038/s41467-018-04049-3info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/388922026-05-27T13:36:21Z
dc.title.none.fl_str_mv Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
title Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
spellingShingle Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
Dhandapani, Rahul
mechanical allodynia
neuropathic pain
TrkB-Cre-expressing neurons
title_short Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
title_full Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
title_fullStr Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
title_full_unstemmed Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
title_sort Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons
dc.creator.none.fl_str_mv Dhandapani, Rahul
Arokiaraj, Cynthia Mary
Taberner, Francisco J
Pacifico, Paola
Raja, Sruthi
Nocchi, Linda
Portulano, Carla
Franciosa, Federica
Maffei, Mariano
Hussain, Ahmad Fawzi
de Castro Reis, Fernanda
REYMOND, Luc
Perlas, Emerald
GARCOVICH, Simone
Barth, Stefan
author Dhandapani, Rahul
author_facet Dhandapani, Rahul
Arokiaraj, Cynthia Mary
Taberner, Francisco J
Pacifico, Paola
Raja, Sruthi
Nocchi, Linda
Portulano, Carla
Franciosa, Federica
Maffei, Mariano
Hussain, Ahmad Fawzi
de Castro Reis, Fernanda
REYMOND, Luc
Perlas, Emerald
GARCOVICH, Simone
Barth, Stefan
author_role author
author2 Arokiaraj, Cynthia Mary
Taberner, Francisco J
Pacifico, Paola
Raja, Sruthi
Nocchi, Linda
Portulano, Carla
Franciosa, Federica
Maffei, Mariano
Hussain, Ahmad Fawzi
de Castro Reis, Fernanda
REYMOND, Luc
Perlas, Emerald
GARCOVICH, Simone
Barth, Stefan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institutos de la UMH::Instituto de Neurociencias
dc.subject.none.fl_str_mv mechanical allodynia
neuropathic pain
TrkB-Cre-expressing neurons
topic mechanical allodynia
neuropathic pain
TrkB-Cre-expressing neurons
description Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment.
publishDate 2018
dc.date.none.fl_str_mv 2018
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/38892
url https://hdl.handle.net/11000/38892
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv 10.1038/s41467-018-04049-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
14
application/pdf
dc.publisher.none.fl_str_mv PMC
publisher.none.fl_str_mv PMC
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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