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Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.

ABSTRACT: Sigma-1 receptor (?1R) 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 ?1R 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-?, interleukin IL-1?) 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 ?1R KO mice following SCI. Accordingly, treatment of WT mice with the ?1R 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 ?1R KO were accompanied by reduced expression of TNF- ? and IL-1? as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that ?1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism.

SUBMITTER: Castany S

PROVIDER: S-EPMC5832850 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.

Castany Sílvia S Gris Georgia G Vela José Miguel JM Verdú Enrique E Boadas-Vaello Pere P

Scientific reports 20180301 1

Sigma-1 receptor (σ<sub>1</sub>R) 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 σ<sub>1</sub>R KO on extracellular mediators and signalling pathways in the spinal co ...[more]

PMID: 29497125

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Project description:Objective: Chronic pain is a major problem in patients with spinal cord injury (SCI). According to different studies, approximately 70% of patients with SCI experience persistent pain. Although previous gene expression profiling studies have been conducted in animal models, gene expression profiling study in human whole blood has not been reported yet. The objective of this study was to define the gene expression profile of neuropathic pain in spinal cord injured patients. Materials and Methods: We performed gene expression analysis including 20.000 genes using Affymetrix GeneChip® Primeview™ Human Gene Expression Arrays. For confirmation of expression levels of selected genes, we performed real time polymerase chain reaction. We gathered samples from periferic blood mononuclear cells. Data of twelve patients with intractable neuropathic pain was compared with thirteen patients who don’t have pain. All patients have complete injuries with a level of injury above T5. Results: A total of 16 differentially expressed genes including 9 up-regulated and 7 down-regulated were obtained with a cut-off degree at 4 fold change. EIF1AY, RPS4Y1, DDX3Y, RPL31, ETS1, KLF3, JUN, CYorf15B, and ERAP2 were in up-regulated and HLA-C, XIST, C4BPA, FAM118A, ZNF506, OVOS2, and C1D were in down-regulated group. KEGG pathway database showed that 14.6% of genes were enriched in the nodes of immune system. Real time polymerase chain reaction analyses did not increase to statistically significant levels for confirmation of gene expression analyze results. Conclusions: Considering these data, findings of this first gene expression study in humans with SCI might provide valuable information for future targets for understanding neuropathic pain pathogenesis. The results of gene expression analyses were not confirmed by real time polymerase chain reaction. Studies with larger sample size are needed for confirmation. This is a cross-sectional study with a control group. Patients were divided into two groups according to intractable neuropathic pain existence.There were 12 patients in group A (Patients with pain) and 13 patients in control group.

Dataset Information

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.

Publications

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.

Similar Datasets

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