Affiliated with Université Laval and the CERVO Research Centre

Spinal microglia are required for long-term maintenance of neuropathic pain.

TitleSpinal microglia are required for long-term maintenance of neuropathic pain.
Publication TypeJournal Article
Year of Publication2017
AuthorsEcheverry S, Shi XQun, Yang M, Huang H, Wu YC, Lorenzo L-E, Perez-Sanchez J, Bonin RP, De Koninck Y, Zhang J
JournalPain
Volume158
Issue9
Pagination1792-1801
Date Published2017 Sep
ISSN1872-6623
Abstract

<p>While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia-neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.</p>

DOI10.1097/j.pain.0000000000000982
Alternate JournalPain
PubMed ID28746078