Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
dc.contributor.author
dc.date.accessioned
2020-10-05T14:04:41Z
dc.date.available
2020-10-05T14:04:41Z
dc.date.issued
2018-03-01
dc.identifier.issn
2045-2322
dc.identifier.uri
dc.description.abstract
Sigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) – a model of central neuropathic pain. The modulatory effect of σ1R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ1R KO mice following SCI. Accordingly, treatment of WT mice with the σ1R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ1R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Nature Research
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Reproducció digital del document publicat a: https://doi.org/10.1038/s41598-018-22217-9
dc.relation.ispartof
Scientific reports, 2018, vol. 8, art. núm. 3873
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Attribution 4.0 International
dc.rights.uri
dc.subject
dc.title
Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
028249
dc.type.peerreviewed
peer-reviewed