Identification of Spinal Circuits Involved in Touch-evoked Dynamic Mechanical Pain

Overview

Journal Nat Neurosci

Date 2017 Apr 25

PMID 28436981

Citations 94

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

Affiliations

Soon will be listed here.

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 (VT3 neurons): the mice lost brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3 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 VT3-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 VT3 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.

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