Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice
dc.contributor.author
dc.date.accessioned
2020-06-15T09:53:07Z
dc.date.available
2020-06-15T09:53:07Z
dc.date.issued
2019-03-22
dc.identifier.uri
dc.description.abstract
Up to two-thirds of patients affected by spinal cord injury (SCI) develop central neuropathic pain (CNP), which has a high impact on their quality of life. Most of the patients are largely refractory to current treatments, and new pharmacological strategies are needed. Recently, it has been shown that the acute administration of the σ1R antagonist MR309 (previously developed as E-52862) at 28 days after spinal cord contusion results in a dose-dependent suppression of both mechanical allodynia and thermal hyperalgesia in wild-type CD-1 Swiss female mice. The present work was addressed to determine whether MR309 might exert preventive effects on CNP development by repeated administration during the first week after SCI in mice. To this end, the MR309 (16 or 32 mg/kg i.p.) modulation on both thermal hyperalgesia and mechanical allodynia development were evaluated weekly up to 28 days post-injury. In addition, changes in pro-inflammatory cytokine (TNF-α, IL-1β) expression 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 analyzed. The repeated treatment of SCI-mice with MR309 resulted in significant pain behavior attenuation beyond the end of the administration period, accompanied by reduced expression of central sensitization-related mechanistic correlates, including extracellular mediators (TNF-α and IL-1β), membrane receptors/channels (NR2B-NMDA) and intracellular signaling cascades (ERK/pERK). These findings suggest that repeated MR309 treatment after SCI may be a suitable pharmacologic strategy to modulate SCI-induced CNP development
dc.description.sponsorship
The present work was supported by the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya, Industrial Doctorates Plan, Government of Catalonia (grant number 2014-DI-026 ESTEVE—Universitat de Girona); the Vice-Chancellorship of Research of the University of Girona (grant number MPCUdG2016/087); and the Agència de Gestió d’Ajuts Universitaris i de Recerca-AGAUR, Government of Catalonia (grant number 2017 SGR 1279)
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
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Reproducció digital del document publicat a: https://doi.org/10.3389/fphar.2019.00222
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Frontiers in Pharmacology , 2019, vol. 10, art.núm. 222
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Articles publicats (D-CM)
dc.rights
Attribution 4.0 International
dc.rights.uri
dc.subject
dc.title
Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After 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
029683
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1663-9812