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

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

Local release of enkephalins by T lymphocytes induces analgesia in IL‐10‐deficient mice with colitis. T cell‐derived opioids may reduce abdominal pain in patients with inflammatory bowel diseases associated with homozygous “loss of function mutations” in IL‐10.

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.