Identification of spinal circuits involved in touch-evoked dynamic mechanical pain.

Abstract

Mechanical hypersensitivity is a debilitating symptom for millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate hypersensitivities. We reduced dynamic mechanical hypersensitivity induced by nerve injury or inflammation in mice by ablating a group of adult spinal neurons defined by developmental co-expression of VGLUT3 and Lbx1 (VT3Lbx1 neurons): the mice lost brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. The subset of somatostatin-lineage neurons preserved in VT3Lbx1-neuron-ablated mice is largely sufficient to mediate morphine-sensitive and morphine-resistant forms of von Frey filament-evoked punctate mechanical hypersensitivity. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting that these neurons may be a cellular target for treating this form of neuropathic pain.

• Authors: Longzhen Cheng, Bo Duan, Tianwen Huang, Yan Zhang, Yangyang Chen, Olivier Britz, Lidia Garcia-Campmany, Xiangyu Ren, Linh Vong, Bradford B Lowell, Martyn Goulding, Yun Wang, Qiufu Ma
• Journal: Nature neuroscience (Nat Neurosci) Vol. 20 Issue 6 Pg. 804-814 (Jun 2017) ISSN: 1546-1726 [Electronic] United States
• PMID: 28436981 (Publication Type: Journal Article)

Chemical References

• Amino Acid Transport Systems, Acidic
• Diphtheria Toxin
• Heparin-binding EGF-like Growth Factor
• Lbx1h protein, mouse
• Muscle Proteins
• vesicular glutamate transporter 3, mouse
• Somatostatin
• Morphine
• Clozapine

Topics

• Action Potentials (drug effects, physiology)
• Amino Acid Transport Systems, Acidic (biosynthesis, genetics, physiology)
• Animals
• Avoidance Learning (physiology)
• Clozapine (pharmacology)
• Diphtheria Toxin (pharmacology)
• Female
• Gene Knock-In Techniques
• Heparin-binding EGF-like Growth Factor (genetics)
• Hyperalgesia (physiopathology)
• Male
• Mice
• Mice, Transgenic
• Morphine (pharmacology)
• Muscle Proteins (biosynthesis)
• Nerve Fibers, Unmyelinated (physiology)
• Neural Pathways (drug effects, physiology)
• Neurons (drug effects, metabolism, physiology)
• Pain Measurement (drug effects)
• Somatostatin (physiology)
• Spinal Cord (drug effects, physiology)
• Touch (physiology)