Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: toward a vaccinal strategy to alleviate inflammatory visceral pain

T lymphocytes play a pivotal role in endogenous regulation of inflammatory visceral pain. The analgesic activity of T lymphocytes is dependent on their production of opioids, a property acquired on antigen activation. Accordingly, we investigated whether an active recruitment of T lymphocytes within inflamed colon mucosa via a local vaccinal strategy may counteract inflammation-induced visceral pain in mice. Mice were immunized against ovalbumin (OVA). One month after immunization, colitis was induced by adding 3% (wt/vol) dextran sulfate sodium into drinking water containing either cognate antigen OVA or control antigen bovine serum albumin for 5 days. Noncolitis OVA-primed mice were used as controls. Visceral sensitivity was then determined by colorectal distension. Oral administration of OVA but not bovine serum albumin significantly reduced dextran sulfate sodium-induced abdominal pain without increasing colitis severity in OVA-primed mice. Analgesia was dependent on local release of enkephalins by effector anti-OVA T lymphocytes infiltrating the inflamed mucosa. The experiments were reproduced with the bacillus Calmette-Guerin vaccine as antigen. Similarly, inflammatory visceral pain was dramatically alleviated in mice vaccinated against bacillus Calmette-Guerin and then locally administered with live Mycobacterium bovis. Together, these results show that the induction of a secondary adaptive immune response against vaccine antigens in inflamed mucosa may constitute a safe noninvasive strategy to relieve from visceral inflammatory pain.