| First Author | Castany S | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 3873 |
| PubMed ID | 29497125 | Mgi Jnum | J:262621 |
| Mgi Id | MGI:6163146 | Doi | 10.1038/s41598-018-22217-9 |
| Citation | Castany S, et al. (2018) Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice. Sci Rep 8(1):3873 |
| abstractText | Sigma-1 receptor (sigma1R) 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 sigma1R 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-alpha, interleukin IL-1beta) 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 sigma1R KO mice following SCI. Accordingly, treatment of WT mice with the sigma1R 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 sigma1R KO were accompanied by reduced expression of TNF- alpha and IL-1beta as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that sigma1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism. |
