Intestinal inflammation and pain management

• Opioid-producing CD4+ T lymphocytes are the main endogenous regulators of visceral pain upon colitis.
• The use of opioids in IBD population is steadily increasing despite severe deleterious side effects.
• To reduce centrally mediated side effects, new therapeutic strategies aim at restricting opioid action at periphery.

Intestinal inflammation results in the production of inflammatory pain-inducing mediators that may directly activate colon sensory neurons. Endogenous opioids produced by mucosal effector CD4+ T lymphocytes identified as colitogenic may paradoxically counterbalance the local pro-algesic effect of inflammatory mediators by acting on opioid receptors expressed on sensory nerve endings. The review will focus on the endogenous immune-mediated regulation of visceral inflammatory pain, current pain treatments in inflammatory bowel diseases and prospectives on new opioid therapeutic opportunities to alleviate pain but avoiding common centrally-mediated side effects.