Microbiota–Brain–Pain: Integrating Gut Biology into the Neuroscience of Chronic Pain

Intestinal dysbiosis, characterized by an imbalance in the composition and function of the microbiota, has been recognized as a key factor in the modulation of chronic pain. Alterations in the microbiome can trigger systemic inflammatory responses, affect intestinal permeability, and directly influence the neuroimmune axes connecting the gut to the central nervous system. The interactions between nervous system and immune system play a pivotal role in modulating microbiota composition and activity, and neuroimmune responses can, in turn, influence dysbiosis, amplifying inflammatory signaling and contributing to persistent pain states. These mechanisms contribute to peripheral and central hypersensitization, perpetuating pain even after the initial insult has resolved.
Understanding how the intestinal microbiota participates in the genesis and maintenance of pain is essential for developing more effective therapeutic strategies. Interventions aimed at restoring microbiota homeostasis—either by maintaining bacterial populations or by targeting specific receptors and/or neuroimmune interactions involved in gut–brain communication—have shown promise in modulating both pain, inflammation and host protection.
In this workshop, we aim to discuss how excessive proteolytic activity at the intestinal mucosa surface affects microbiota biofilms and can perpetuate inflammatory conditions, as observed in Crohn’s disease, enhancing tissue damage and neural sensitization. We will discuss how pain and the neuroimmune crosstalk modulate immune responses and host protection.Furthermore, we will explore the mechanisms linking dysbiosis, immune response, and pain in inflammatory bowel diseases and extend the discussion to other pain conditions, including migraine associated with intracranial hypertension, highlighting how the microbiota–immune–gut–brain axis transcends gastrointestinal boundaries and emerges as a cornerstone in understanding and managing chronic pain.