Back to Search
Start Over
Intestinal inflammation-associated hypersensitivity is attenuated in a DSS model of colitis in Sigma-1 knockout C57BL/6 mice.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Nov; Vol. 143, pp. 112126. Date of Electronic Publication: 2021 Aug 30. - Publication Year :
- 2021
-
Abstract
- Sigma-1 receptors (σ <subscript>1</subscript> R) have been implicated in several pain pathways. We assessed the implication of σ <subscript>1</subscript> Rs in the development of intestinal inflammation and inflammation-associated referred hypersensitivity in a model of colitis in σ <subscript>1</subscript> R knockout (KO) mice. Colitis was induced with dextran sulfate sodium (DSS) in wild type (WT) and σ <subscript>1</subscript> R 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 σ <subscript>1</subscript> Rs 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 σ <subscript>1</subscript> R 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 σ <subscript>1</subscript> R 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 σ <subscript>1</subscript> -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 σ <subscript>1</subscript> R KO mice, thus confirming an important role for σ <subscript>1</subscript> R in the development of colitis-associated hypersensitivity. These results identify σ <subscript>1</subscript> Rs as a possible therapeutic target for the treatment of hypersensitivity associated to intestinal inflammation.<br /> (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Colitis chemically induced
Colitis genetics
Colitis physiopathology
Colon innervation
Dextran Sulfate
Disease Models, Animal
Hyperalgesia genetics
Hyperalgesia metabolism
Hyperalgesia physiopathology
Inflammation Mediators metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Receptors, sigma genetics
Signal Transduction
Spinal Cord physiopathology
Sigma-1 Receptor
Mice
Colitis metabolism
Colon metabolism
Hyperalgesia prevention & control
Pain Threshold
Receptors, sigma deficiency
Spinal Cord metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 143
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 34474349
- Full Text :
- https://doi.org/10.1016/j.biopha.2021.112126