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

Rahul Dhandapani, Cynthia Mary Arokiaraj, Francisco J. Taberner, Paola Pacifico, Sruthi Raja, Linda Nocchi, Carla Portulano, Federica Franciosa, Mariano Maffei, Ahmad Fawzi Hussain, Fernanda Castro Reis, Luc Reymond, Emerald Perlas, Simone Garcovich, Stefan Barth, Kai Johnsson, Stefan G. Lechner and Paul A. Heppenstall ()
Additional contact information
Rahul Dhandapani: Epigenetics and Neurobiology Unit, EMBL Rome
Cynthia Mary Arokiaraj: Epigenetics and Neurobiology Unit, EMBL Rome
Francisco J. Taberner: Heidelberg University
Paola Pacifico: Epigenetics and Neurobiology Unit, EMBL Rome
Sruthi Raja: Epigenetics and Neurobiology Unit, EMBL Rome
Linda Nocchi: Epigenetics and Neurobiology Unit, EMBL Rome
Carla Portulano: Epigenetics and Neurobiology Unit, EMBL Rome
Federica Franciosa: Epigenetics and Neurobiology Unit, EMBL Rome
Mariano Maffei: Epigenetics and Neurobiology Unit, EMBL Rome
Ahmad Fawzi Hussain: University Hospital RWTH Aachen
Fernanda Castro Reis: Epigenetics and Neurobiology Unit, EMBL Rome
Luc Reymond: National Centre of Competence in Research (NCCR) in Chemical Biology
Emerald Perlas: Epigenetics and Neurobiology Unit, EMBL Rome
Simone Garcovich: Catholic University of the Sacred Heart
Stefan Barth: University of Cape Town
Kai Johnsson: Max-Planck Institute for Medical Research
Stefan G. Lechner: Heidelberg University
Paul A. Heppenstall: Epigenetics and Neurobiology Unit, EMBL Rome

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04049-3

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