Central Modulation of Visceral Pain Hypersensitivity.

PhD ThesisBackground: visceral pain hypersensitivity is a key feature in functional gastrointestinal conditions. This condition leads to an exaggerated response to known painful stimuli, or chronic pain with no apparent trigger. There is an important paucity of effective clinical interventions for visceral pain hypersensitivity. Aim: To understand the central nervous system (CNS) control of visceral pain hypersensitivity via descending pain pathways to the spinal cord. Additionally, I aim to test the feasibility of a non-pharmacological intervention such as non-invasive vagal nerve stimulation to reduce this condition in healthy humans. Methods: I used PRISMA guidelines for systemtic review and meta-analysis to investigate: i) decending pain control in visvceral pain, ii) The antinociceptive effect of vagal nerve stimulation. To investigate the descending pain control, I used a Conditioned Pain Modulation Paradigm where applying a second painful sitmuls inhibits the initial pain by triggering descending inhibiton. To test the effect of autonomic modulation on oesophageal pain hypersensitivity, I used a previously approved noninvasive transcutaneous vagal nerve stimulation device in a human model of experimentally induced pain hypersensitivity by slow infusion of hydrochloric acid in the distal oesophagus. Results: My systematic review and meta-analysis demonstrated that Conditioned Pain Modulation is significantly inhibited in visceral pain hypersensitivity. I also showed that a reduced Conditioned Pain Modulation at baseline is a strong predictive factor of developing pain hypersensitivity in healthy humans. I also demonstrated that vagal nerve stimulation is effective in various pain conditions in a meta-analysis, I then demonstrated in an experimental study that vagal nerve stimulation can reverse acid-induced oesophageal pain hypersensitivity. Conclusions: there is a marked reduction in descending pain inhibition in visceral pain hypersensitivity. Poor descending pain inhibition is associated with developing experimental pain hypersensitivity. Vagal nerve stimulation can reverse experimental pain hypersensitivity, likely by a central mechanism