Intestinal inflammation-associated hypersensitivity is attenuated in a DSS model of colitis in Sigma-1 knockout C57BL/6 mice
López-Estévez, Sergio (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gris, Georgia (Laboratoris Esteve)
Puente, Beatriz de la (Laboratoris Esteve)
Carceller, Alicia (Laboratoris Esteve)
Martínez Perea, Vicente (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Fecha:	2021
Resumen:	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.
Nota:	Altres ajuts: acords transformatius de la UAB
Nota:	Ajuts: The present work was funded by Laboratories ESTEVE, Barcelona, Spain
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Colitis ; Hyperalgesia ; Hypersensitivity ; Intestinal inflammation ; Pain ; Sigma 1 receptor
Publicado en:	Biomedicine & pharmacotherapy, Vol. 143 (November 2021) , art. 112126, ISSN 1950-6007

DOI: 10.1016/j.biopha.2021.112126
PMID: 34474349

11 p, 2.6 MB

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