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Microglia-independent peripheral neuropathic pain in male and female mice

Tu, YuShan; Muley, Milind M; Beggs, Simon; Salter, Michael W; (2022) Microglia-independent peripheral neuropathic pain in male and female mice. Pain , 163 (11) e1129-e1144. 10.1097/j.pain.0000000000002643. Green open access

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Abstract

ABSTRACT: The dominant view in the field of pain is that peripheral neuropathic pain is driven by microglia in the somatosensory processing region of the spinal dorsal horn. Here, to the contrary, we discovered a form of neuropathic pain that is independent of microglia. Mice in which the nucleus pulposus (NP) of the intervertebral disc was apposed to the sciatic nerve developed a constellation of neuropathic pain behaviours: hypersensitivity to mechanical, cold, and heat stimuli. However, NP application caused no activation of spinal microglia nor was pain hypersensitivity reversed by microglial inhibition. Rather, NP-induced pain hypersensitivity was dependent on cells within the NP which recruited macrophages to the adjacent nerve. Eliminating macrophages systemically or locally prevented NP-induced pain hypersensitivity. Pain hypersensitivity was also prevented by genetically disrupting the neurotrophin brain-derived neurotrophic factor selectively in macrophages. Moreover, the behavioural phenotypes as well as the molecular mechanisms of NP-induced pain hypersensitivity were not different between males and females. Our findings reveal a previously unappreciated mechanism for by which a discrete peripheral nerve lesion may produce pain hypersensitivity, which may help to explain the limited success of microglial inhibitors on neuropathic pain in human clinical trials.

Type: Article
Title: Microglia-independent peripheral neuropathic pain in male and female mice
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/j.pain.0000000000002643
Publisher version: http://dx.doi.org/10.1097/j.pain.0000000000002643
Language: English
Additional information: Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-Non CommercialNo Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Keywords: Science & Technology, Life Sciences & Biomedicine, Anesthesiology, Clinical Neurology, Neurosciences, Neurosciences & Neurology, Neuropathic pain, Macrophages, Microglia, Nerve injury, BDNF, NUCLEUS PULPOSUS CELLS, DORSAL-ROOT GANGLIA, DOUBLE-BLIND, SPINAL-CORD, MECHANICAL ALLODYNIA, INTERVERTEBRAL DISC, SYNAPSE FORMATION, NERVE INJURY, MINOCYCLINE, MACROPHAGES
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10159363
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