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Nat Neurosci. 2017 Jun;20(6):804-814. doi: 10.1038/nn.4549. Epub 2017 Apr 24.

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

Author information

1
Institute of Brain Science, the State Key Laboratory of Medical Neurobiology and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
2
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
3
Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, China.
4
Molecular Neurobiology Laboratory, the Salk Institute for Biological Studies, La Jolla, California, USA.
5
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

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.

PMID:
28436981
PMCID:
PMC5470641
DOI:
10.1038/nn.4549
[Indexed for MEDLINE]
Free PMC Article

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