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Neuron. 2015 Aug 19;87(4):797-812. doi: 10.1016/j.neuron.2015.07.029.

Dorsal Horn Circuits for Persistent Mechanical Pain.

Author information

1
Departments of Neurobiology and Otolaryngology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
2
Departments of Neurobiology and Otolaryngology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Tsinghua M.D. Program, Tsinghua University School of Medicine, 30 Shuang Qing Road, Haidian District, Beijing 100084, China.
3
Departments of Neurobiology and Otolaryngology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA.
4
Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
5
Departments of Neurobiology and Otolaryngology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address: rpseal@pitt.edu.

Abstract

Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.

PMID:
26291162
PMCID:
PMC4562334
DOI:
10.1016/j.neuron.2015.07.029
[Indexed for MEDLINE]
Free PMC Article

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