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Nat Commun. 2018 Apr 24;9(1):1640. doi: 10.1038/s41467-018-04049-3.

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

Author information

1
Epigenetics and Neurobiology Unit, EMBL Rome, Via Ramarini 32, Monterotondo, 00015, Italy.
2
Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
3
Institute of Pharmacology, Heidelberg University, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany.
4
Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstrasse 30, Aachen, 52074, Germany.
5
Ecole Polytechnique Federale de Lausanne, Institute of Chemical Sciences and Engineering (ISIC), Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, Lausanne, 1015, Switzerland.
6
Institute of Dermatology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, Rome, 00168, Italy.
7
South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, South Africa.
8
Department of Chemical Biology, Max-Planck Institute for Medical Research, Heidelberg, 69120, Germany.
9
Epigenetics and Neurobiology Unit, EMBL Rome, Via Ramarini 32, Monterotondo, 00015, Italy. paul.heppenstall@embl.it.
10
Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany. paul.heppenstall@embl.it.

Abstract

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.

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PMID:
29691410
PMCID:
PMC5915601
DOI:
10.1038/s41467-018-04049-3
[Indexed for MEDLINE]
Free PMC Article

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