Chronic painful autoimmune disorders such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) induce significant discomfort. They are defined by persistent inflammation and immune-mediated tissue injury. The activation and sensitisation of nociceptors, mutated in various disorders, are fundamental components contributing to the pain experienced in these conditions. Recent discoveries indicate that immunological mediators and nociceptive receptors interact functionally within peripheral and central sensitisation pathways, amplifying chronic pain. This research examines the involvement of nociceptors in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. It explores how immune cells and pro-inflammatory cytokines induce, sensitise and regulate various nociceptive receptors (P2X, TRPA1 and TRPV1). Finally, we address possible future directions with respect to the treatment of long-lasting effects on immunity, and what new drug targets could be pursued as well, in order to counteract such either neuro-immune interactions in conditions involving the immunological system. By studying nociceptive mechanisms across autoimmune illnesses, we want to identify shared pathways and activation of nociceptors specific to individual diseases. This will shed insight on potential therapies for managing pain associated with autoimmune diseases.© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
