Endogenous control of inflammatory visceral pain by T cell-derived opioids in IL-10-deficient mice

  • Neurogastroenterol Motil. 2020 Feb;32(2):e13743. doi: 10.1111/nmo.13743.
Lilian Basso  1 ,  Mehdi Benamar  2 ,  Xavier Mas-Orea  1 ,  Céline Deraison  1 ,  Catherine Blanpied  1 ,  Nicolas Cenac  1 ,  Abdelhadi Saoudi  2 ,  Gilles Dietrich  1
Affiliations
  • 1. IRSD, INSERM, INRA, ENVT, UPS, Université de Toulouse, Toulouse, France.
  • 2. Centre de Physiopathologie de Toulouse Purpan (CPTP), UPS, INSERM, CNRS, Université de Toulouse, Toulouse, France.
PMID: 31588671 DOI: 10.1111/nmo.13743
Abstract

Background: The opioid-mediated analgesic activity of mucosal CD4+ T lymphocytes in colitis has been reported in immunocompetent mice so far. Here, we investigated whether CD4+ T lymphocytes alleviate from inflammation-induced abdominal pain in mice with defective immune regulation.

Methods: Endogenous control of visceral pain by opioids locally produced in inflamed mucosa was assessed in IL-10-deficient mice.

Key results: CD4+ T lymphocytes but not F4/80+ macrophages isolated from the lamina propria of IL-10-deficient mice with colitis express enkephalin-containing opioid peptides as assessed by cytofluorometry. Colitis in IL-10-/- mice was not associated with abdominal pain. Intraperitoneal injection of naloxone-methiodide, a peripheral Opioid Receptor Antagonist, induced abdominal hypersensitivity in IL-10-/- mice with colitis.

Conclusion and inferences: Opioid-mediated analgesic activity of mucosal T lymphocytes remains operating in IL-10-/- mice with impaired immune regulation. The data suggest that endogenous T cell-derived opioids might reduce inflammation-induced abdominal pain in inflammatory bowel diseases associated with homozygous "loss of function mutations" in interleukin-10.

Keywords
IL10−/− mice; T lymphocytes; intestinal inflammation; opioids; visceral pain.
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