The passive transfer of immunoglobulin G serum antibodies from patients with longstanding Complex Regional Pain Syndrome

Background: The aetiology of Complex Regional Pain Syndrome (CRPS) is unknown. Recent evidence suggests that there may be autoantibodies directed against peripheral nerves, but it is unclear whether such autoantibodies are merely biomarkers or whether they cause or contribute to the underlying pathology. The transfer of disease after injection of a patient's serum or IgG fraction into mice (‘passive transfer’) is the classic way to demonstrate a functional role of autoantibodies. Aims: Based on previous preliminary results, we wished to investigate whether the transfer of IgG antibodies affected mouse behaviour or produced signs of CRPS. Methods: We injected purified serum‐IgG from 12 patients and 12 controls into groups of 6–10 mice (～17 mg/mouse intraperitoneally) on 2 consecutive days and looked for any evidence for altered behaviour or signs of CRPS. The observer, blinded as to test or control group, measured behaviour in the open field, stimulus‐evoked pain and motor coordination, and inspected limbs for autonomic CRPS signs. Results: Stimulus‐evoked pain and autonomic signs were not detected, but CRPS‐IgG induced significant depression of rearing behaviour (17.9 rears/3 min (n =84) vs. 22.1 rears/3 min (n =83), p =0.0004), confirming previous observations in a single case study. Moreover, motor impairment, one of the four cardinal signs of CRPS, was evident in the three CRPS‐IgG injected groups tested with a sensitive rota‐rod protocol (p <0.0001 vs. control‐IgG injected groups). Conclusions: These results lend support to a pathophysiological role for IgG autoantibodies in CRPS.