Autonomic Receptor Autoantibodies in Complex Regional Pain Syndrome and Other Chronic Pain Conditions: A Cross-Sectional Analysis

Objectives: Complex regional pain syndrome (CRPS) is a heterogeneous pain disorder with incompletely understood immunoinflammatory features. This study investigated whether autonomic receptor autoantibodies differentiate CRPS from other chronic pain conditions and healthy controls. Methods: We conducted a cross-sectional analysis of serum samples from patients referred with suspected CRPS. Patients were subsequently classified as having either CRPS or another chronic pain condition, based on the Budapest criteria. Healthy controls were included for comparison. Serum levels of autoantibodies targeting the muscarinic M2 receptor (M2R), β1-adrenergic receptor (β1AR), and the β2-adrenergic receptor (β2AR) were assessed using enzyme-linked immunosorbent assay. All analyses were performed blinded to group assignment. Results: Seventy participants were analyzed (CRPS = 22, other chronic pain = 25, healthy controls = 23). M2R autoantibody levels were higher in both CRPS and other chronic pain compared with healthy controls (mean difference [MD] = 0.37, 95%CI 0.22–0.51; and MD = 0.31 95%CI 0.19–0.44, respectively). β2AR levels were higher in other chronic pain compared with healthy controls (MD = 0.29, 95%CI 0.04–0.54), whereas no significant difference was observed in CRPS (MD = 0.21 95%CI −0.01–0.42). No meaningful differences were observed between CRPS and other chronic pain for any receptor. β1AR levels did not differ between groups. Seropositivity for any autoantibody was 55% in CRPS, 44% in other chronic pain, and 22% in healthy controls. Conclusions: Elevated autonomic receptor autoantibody levels were observed across chronic pain conditions but were not specific for CRPS.