The transition from acute to persistent pain is a devastating journey, creating a state of suffering that has long eluded objective measurement and effective treatment. While our understanding has evolved to embrace the central nervous system's neuroimmune adaptations, the role of the adaptive immune system, specifically B cells, has remained largely unexplored. This presentation will introduce a paradigm-shifting hypothesis: that B cells are not merely bystanders but are critical orchestrators in the pathology of persistent pain.
The B Cell Hypothesis of Pain: Drawing on recent groundbreaking preclinical evidence, we demonstrate that the development of neuropathic pain is critically dependent on B cells and their production of Immunoglobulin G (IgG). In animal models, the depletion of B cells at the time of nerve injury completely prevents the onset of pain-like behaviours. Furthermore, IgG isolated from nerve-injured subjects is sufficient to induce pain hypersensitivity when transferred to pain-free recipients, but only in the presence of an underlying nerve injury. This suggests the generation of injury-specific, pathogenic autoantibodies. These findings are supported by evidence of IgG accumulation and a B cell transcriptional signature in the dorsal root ganglia of human donors with a history of chronic pain.
Objective Measurement and Therapeutic Potential: This B cell-IgG-FcγR signalling axis provides a tangible, measurable biological process outside of the central nervous system. It presents a novel opportunity to explain the first objective, blood-based biomarkers for persistent pain by quantifying blood-based factors. By viewing persistent pain through an autoimmune lens, we uncover a powerful new framework for diagnostics and therapeutics. This presentation will equip attendees with insights into this novel mechanism, challenging our neuron-centric view and opening the door to immunotherapies that could prevent or reverse one of medicine's most intractable conditions.