Research Intern at Mayo Clinic Mayo Clin., Arizona Chandler, Arizona, United States
Introduction/Rationale: Endometriosis is a chronic inflammatory disease redefined as a neuroimmune pain syndrome. Pain arises from neuroimmune crosstalk, driving peripheral and central sensitization. Sensory nerves release SP and CGRP, amplifying inflammation and lesion growth. This abstract proposes that B cell–derived IgG autoantibodies trigger neuropathic pain through the FcγR axis, linking neurons, macrophages, and microglia—offering a new immunomodulatory target.
Methods: Therapeutic strategies target the B cell–FcγR axis to modulate neuroimmune pain in endometriosis. Approaches include B cell depletion with anti-CD20 antibodies, FcγR or BTK inhibition, and blockade of neuropeptides such as CGRP and SP. Additional options include TRPV1 antagonists and NGF/BDNF neutralization to reduce hyperinnervation, inflammation, and neuropathic pain.
Results: Immunomodulatory and neuro-targeted therapies show promise beyond hormonal treatments. Targeting the B cell–FcγR axis with anti-CD20 antibodies, BTK inhibitors, or FcγR antagonists may reduce cytokine release and IgG-mediated neuropathic pain. Blocking CGRP-RAMP1 signaling lessens hyperalgesia and lesion growth, while TRPV1, NGF, and BDNF inhibition can desensitize nerves and reduce inflammation.
Conclusion: Endometriosis involves intertwined neuroimmune and inflammatory pathways driving chronic pain. Neurogenic inflammation, hyperinnervation, and immune dysregulation sustain sensitization. B cell–derived IgG autoantibodies acting through the FcγR axis may trigger neuropathic pain and glial activation, linking peripheral inflammation to central sensitization and chronic pelvic pain.
