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.

Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons / 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; Johnsson, Kai; Lechner, Stefan G.; Heppenstall, Paul A.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 9:1(2018), pp. 1-14. [10.1038/s41467-018-04049-3]

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

Heppenstall, Paul A.
2018

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.
9
1
1
14
1640
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; Johnsson, Kai; Lechner, Stefan G.; Heppenstall, Paul A.
File in questo prodotto:
File Dimensione Formato  
s41467-018-04049-3.pdf

accesso aperto

Descrizione: Open Access
Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 4.11 MB
Formato Adobe PDF
4.11 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/87758
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 49
  • ???jsp.display-item.citation.isi??? 47
social impact