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Optogenetic inhibition of the colon epithelium reduces hypersensitivity in a mouse model of inflammatory bowel disease.
Najjar, Sarah A; Ejoh, Lindsay L; Loeza-Alcocer, Emanuel; Edwards, Brian S; Smith-Edwards, Kristen M; Epouhe, Ariel Y; Gold, Michael S; Davis, Brian M; Albers, Kathryn M.
Afiliación
  • Najjar SA; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  • Ejoh LL; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, United States.
  • Loeza-Alcocer E; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, United States.
  • Edwards BS; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  • Smith-Edwards KM; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  • Epouhe AY; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, United States.
  • Gold MS; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, United States.
  • Davis BM; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  • Albers KM; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, United States.
Pain ; 162(4): 1126-1134, 2021 04 01.
Article en En | MEDLINE | ID: mdl-33048854
ABSTRACT: Visceral pain is a prevalent symptom of inflammatory bowel disease that can be difficult to treat. Pain and hypersensitivity are mediated by extrinsic primary afferent neurons (ExPANs) that innervate the colon. Recent studies indicate that the colon epithelium contributes to initiating ExPAN firing and nociceptive responses. Based on these findings, we hypothesized that the epithelium contributes to inflammation-induced hypersensitivity. A key prediction of this hypothesis is that inhibition of the epithelium would attenuate nociceptive signaling and inflammatory hypersensitivity. To test this hypothesis, the inhibitory yellow light-activated protein archaerhodopsin was targeted to the intestinal epithelium (villin-Arch) or the ExPANs (TRPV1-Arch) that innervate the colon. Visceral sensitivity was assessed by measuring the visceromotor response (VMR) to colorectal distension (CRD), with and without yellow light illumination of the colon lumen. Inhibition of the colon epithelium in healthy villin-Arch mice significantly diminished the CRD-induced VMR. Direct inhibition of ExPANs during CRD using TRPV1-Arch mice showed that ExPAN and epithelial inhibition were similarly effective in reducing the VMR to CRD. We then investigated the effect of epithelial and ExPAN inhibition in the dextran sulfate sodium model of inflammatory bowel disease. Inhibition of the colon epithelium significantly decreased dextran sulfate sodium-induced hypersensitivity and was comparable with the inhibition of ExPANs. Together, these results reveal the potential of targeting the colon epithelium for the treatment of pain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Optogenética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pain Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Optogenética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pain Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos