TY - JOUR
T1 - Intestinal inflammation-associated hypersensitivity is attenuated in a DSS model of colitis in Sigma-1 knockout C57BL/6 mice
AU - López-Estévez, Sergio
AU - Gris, Georgia
AU - de la Puente, Beatriz
AU - Carceller, Alicia
AU - Martínez, Vicente
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Sigma-1 receptors (σ1R) have been implicated in several pain pathways. We assessed the implication of σ1Rs in the development of intestinal inflammation and inflammation-associated referred hypersensitivity in a model of colitis in σ1R knockout (KO) mice. Colitis was induced with dextran sulfate sodium (DSS) in wild type (WT) and σ1R 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 σ1Rs 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 σ1R 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 σ1R 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 σ1-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 σ1R KO mice, thus confirming an important role for σ1R in the development of colitis-associated hypersensitivity. These results identify σ1Rs as a possible therapeutic target for the treatment of hypersensitivity associated to intestinal inflammation.
AB - Sigma-1 receptors (σ1R) have been implicated in several pain pathways. We assessed the implication of σ1Rs in the development of intestinal inflammation and inflammation-associated referred hypersensitivity in a model of colitis in σ1R knockout (KO) mice. Colitis was induced with dextran sulfate sodium (DSS) in wild type (WT) and σ1R 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 σ1Rs 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 σ1R 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 σ1R 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 σ1-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 σ1R KO mice, thus confirming an important role for σ1R in the development of colitis-associated hypersensitivity. These results identify σ1Rs as a possible therapeutic target for the treatment of hypersensitivity associated to intestinal inflammation.
KW - Colitis
KW - Hyperalgesia
KW - Hypersensitivity
KW - Intestinal inflammation
KW - Pain
KW - Sigma 1 receptor
UR - http://www.scopus.com/inward/record.url?scp=85113880138&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/9b68c858-863b-3fdd-9994-81125ef90f58/
U2 - 10.1016/j.biopha.2021.112126
DO - 10.1016/j.biopha.2021.112126
M3 - Article
C2 - 34474349
SN - 0753-3322
VL - 143
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 112126
ER -