Very little is known about the molecular mechanisms underlying chronic neck pain, a highly prevalent and burdensome condition. We analyzed the C2 dorsal root ganglion (DRG) of patients with neck pain who underwent C1-2 arthrodesis surgery. Using spatial transcriptomics, we provide the first report of IGHG4 expression in a human DRG. IGHG4 encodes immunoglobulin G4 (IgG4). Infiltration of IgG4-producing lymphocytes characterizes IgG4-related disease, an immune-mediated inflammatory condition, and IgG4 autoantibodies sensitize DRG sensory neurons. The expression was found only in one of the 8 patients analyzed, was very high, and co-localized with B cells, which have a crucial role in IgG4 production. The findings uncover a molecular mechanism potentially involved in chronic neck pain in patients susceptible to infiltration of IgG4-producing B cells.

The authors have declared no competing interest.

This study was funded by: NIH: 1R01AR078192-01A1 NIH: U19NS130608 NIH: University of Washington Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research. CLEAR is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (Award Number P30AR072572). NIH R01 NS126252 Department of Defense, Peer Reviewed Medical Research Program Award Number HT9425-24-1-0109

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The study was approved by the University of Washington Internal Review Board (study 10916).

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All data produced in the present study are available upon reasonable request to the authors