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

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.