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

Dhandapani, R., Arokiaraj, C. M., Taberner, F. J., Pacifico, P., Raja, S., Nocchi, L., et al. (2018). Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons. Nature Communications, 2018(9): 1640, pp. 1-14. doi:10.1038/s41467-018-04049-3.

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Dhandapani, Rahul, Author
Arokiaraj, Cynthia Mary, Author
Taberner, Francisco J., Author
Pacifico, Paola, Author
Raja, Sruthi, Author
Nocchi, Linda, Author
Portulano, Carla, Author
Franciosa, Federica, Author
Maffei, Mariano, Author
Hussain, Ahmad Fawzi, Author
de Reis, Fernanda Castro, Author
Reymond, Luc, Author
Perlas, Emerald, Author
Garcovich, Simone, Author
Barth, Stefan, Author
Johnsson, Kai1, Author           
Lechner, Stefan G., Author
Heppenstall, Paul A., Author
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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 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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Language(s): eng - English
 Dates: 2018-04-242018-04-24
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-018-04049-3
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 2018 (9) Sequence Number: 1640 Start / End Page: 1 - 14 Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723