Inserm researchers have recently shown that it is possible to alleviate inflammatory intestinal pain in mice by vaccinating them. In this strategy, T cells are pre-activated to acquire the ability to produce opioids, following which they are drawn to the pain site.
Immunizing against pain is a novel idea to say the least, but Inserm* researchers show that it is far from being a utopia. They have indeed recently proven, in mice, that a vaccination can alleviate visceral pain.
This research avenue was explored in 2011, when it was shown that T cells activated by a bacterial antigen in a lymph node acquired the ability to produce opioids. When migrating to the lesion site, they release these opioids locally if the bacterial antigen were still present. “When the T cells arrive on the scene, the wound is still infected, although the adaptive immune response is in place, making it possible to alleviate pain,” explains research leader Gilles Dietrich. “Pain is basically just a warning signal so that we can take action against harm threatening our body.” But this is referring to a process triggered by infection. What about inflammatory pain?
In answer to this question, his team studied the case of chronic inflammatory intestinal diseases in 2014. The researchers induced severe intestinal inflammation in mice and observed that the arrival of T cells activated by the intestinal bacteria to the lesion site was consistent with an alleviation of pain. Based on these findings, they supposed that a vaccine strategy to speed up the arrival of the pre-activated T cells could serve to alleviate pain in certain situations.
The hypothesis developed by Dietrich and his coworkers involved stimulating T cells using a vaccine to create a pool of memory lymphocytes. A pool which can be rapidly reactivated by injecting, at the site of the inflammation, antigens that correspond to the vaccine. The pre-activated T cells are then very quick to arrive on the scene and release their opioids.
To test this, the researchers vaccinated mice with BCG, a vaccine used against the tuberculosis-causing agent Mycobacterium tuberculosis. Several days later, they induced intestinal inflammation with the help of an orally administered substance to which they had added Mycobacterium tuberculosis. Whereas the control mice had to wait over five days before experiencing some alleviation of their pain, the vaccinated mice saw a rapid and very marked decrease in theirs. The authors also took care to check that the early recruitment of T cells did not alter the intestinal tissue or increase the lesions.
Although it is difficult to imagine vaccinating people against hypothetical pain, this strategy could be applied in very specific scenarios. For example, in the event of scheduled surgery for anastomosis. “This procedure, which involves removing a portion of the intestine, triggers severe inflammation. It requires the administration of morphine to relieve the pain. Why not check the patient's vaccine status and inject antigens - which correspond to a vaccine already administered - at the surgery site prior to the procedure, to attract the T cells to the region and enable the liberation of opioids there? If successful, it would mean not having to administer so much morphine, which, given its central action, can have considerable side effects," says Dietrich.
*Unit 1220 Inserm/Inra/Université Paul Sabatier/French National Veterinary School, Intestinal Neuroimmune Reactions team, Institute of Research in Digestive Health, Toulouse
L. Basso et coll. Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: towards a vaccinal strategy to alleviate inflammatory visceral pain. Pain, édition du 13 novembre 2017