Regulation of abdominal pain by colitogenic T cells

▸ Boué J, Basso L, Cenac N, et al. Endogenous regulation of visceral pain via production of opioids by colitogenic CD4(+) T cells in mice. Gastroenterology 2014;146:166–75.

Severe abdominal pain represents a major symptom among patients with inflammatory bowel disease (IBD). IBD is largely attributed to a dysregulated response of effector CD4 cells against the microbiota. Accumulation of effector CD4 T cells at the site of a microbe infection leads to increased opioid synthesis to relieve somatic pain; however, whether this opioid production also occurs in the context of intestinal inflammation is unknown. In this study, Boué and colleagues set out to investigate whether colitogenic CD4 T cells that accumulate in the inflamed colon also produce opioids and are able to counteract inflammation-induced visceral pain in mice. Colitis was induced via transfer of naïve CD4 T cells to immune-deficient mice or by administration of dextran sulfate sodium. In the T cell-mediated model, TH1 and TH17 cells accumulating in inflamed intestinal mucosa produced opioids. Opioid mRNA was highly expressed in mucosal T cells but not in naïve CD4 cells before their transfer, suggesting that the ability to produce opioids is acquired upon activation of colitogenic CD4 T cells. Blocking the peripheral opioid receptor increased visceral sensitivity; therefore, stimulation of opioid receptors by endogenous opioids locally released in the inflamed intestine inhibits inflammation-induced visceral pain. The analgesic property of colitogenic T cells was also demonstrated in the mucosal-damage model of acute DSS-induced colitis. This study makes the paradoxical finding that proinflammatory colitogenic CD4 cells promote intestinal inflammation and colonic tissue damage, but concomitantly produce an opioid-mediated analgesic effect that reduces the pain associated with intestinal inflammation. Since severe abdominal pain is a symptom that would warrant an exam by a physician, the analgesic properties of colitogenic T cells may be harmful to …