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

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.

• Authors: Rahul Dhandapani, Cynthia Mary Arokiaraj, Francisco J Taberner, Paola Pacifico, Sruthi Raja, Linda Nocchi, Carla Portulano, Federica Franciosa, Mariano Maffei, Ahmad Fawzi Hussain, Fernanda de Castro Reis, Luc Reymond, Emerald Perlas, Simone Garcovich, Stefan Barth, Kai Johnsson, Stefan G Lechner, Paul A Heppenstall
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 1640 (04 24 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 29691410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Ligands
• Membrane Glycoproteins
• Ntrk2 protein, mouse
• Protein-Tyrosine Kinases

Topics

• Animals
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Female
• Humans
• Hyperalgesia (genetics, metabolism, physiopathology, therapy)
• Laser Therapy
• Ligands
• Male
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Neuralgia (genetics, metabolism, physiopathology, therapy)
• Protein-Tyrosine Kinases (genetics, metabolism)
• Sensory Receptor Cells (metabolism, radiation effects)
• Touch (radiation effects)