| First Author | López-Estévez S | Year | 2021 |
| Journal | Biomed Pharmacother | Volume | 143 |
| Pages | 112126 | PubMed ID | 34474349 |
| Mgi Jnum | J:322081 | Mgi Id | MGI:6810642 |
| Doi | 10.1016/j.biopha.2021.112126 | Citation | Lopez-Estevez S, et al. (2021) Intestinal inflammation-associated hypersensitivity is attenuated in a DSS model of colitis in Sigma-1 knockout C57BL/6 mice. Biomed Pharmacother 143:112126 |
| abstractText | Sigma-1 receptors (sigma1R) have been implicated in several pain pathways. We assessed the implication of sigma1Rs in the development of intestinal inflammation and inflammation-associated referred hypersensitivity in a model of colitis in sigma1R knockout (KO) mice. Colitis was induced with dextran sulfate sodium (DSS) in wild type (WT) and sigma1R KO mice. The development of referred mechanical hypersensitivity (von Frey test) was assessed. Colonic and spinal changes in expression of immune- and sensory-related markers were also investigated (RT-qPCR/Western blot). Absence of sigma1Rs had little impact in colitis generation and progression, although during the chronic phase a reduction in edema and a down-regulation of iNOS gene expression was observed. In sigma1R KO mice, inflammation-associated hypersensitivity was significantly attenuated (paw) or completely prevented (abdomen). During colitis, in WT mice, changes in the colonic expression of nociceptive markers were observed during the acute and chronic phases of inflammation. Although sigma1R KO mice showed similar regulation in the acute phase, an attenuated response was observed during the chronic phase of colitis. These differences were especially relevant for CB2 and TRPV1 receptors, which could play an important role in sigma1-mediated regulation of sensitivity. No changes were detected on ERK phosphorylation at the level of the lumbosacral spinal cord. In summary, intestinal inflammation-associated referred hyperalgesia was reduced (paw) or absent (abdomen) in sigma1R KO mice, thus confirming an important role for sigma1R in the development of colitis-associated hypersensitivity. These results identify sigma1Rs as a possible therapeutic target for the treatment of hypersensitivity associated to intestinal inflammation. |
