Anti-autonomic autoantibodies had already been detected previously in serum samples from patients with short-term
CRPS . To ascertain buy EX 527 anti-autonomic autoantibodies in long-standing CRPS patients, a laboratory study was carried out using a novel adult cardiomyocyte model . Although cardiomyocytes are not involved in the CRPS pathophysiology, these cells are useful for detecting autoantibodies directed against autonomic receptors, as any functional receptor effect will be indicated by changes in the pattern of the cardiomyocytes’ beatings. Cardiomyocytes treated with serum-IgG preparations from CRPS patients and controls (29 healthy patients, seven with neuropathic pain, nine with myasthenia and 12 with fibromyalgia) were placed into a pulsating electric field to induce calcium influx and contraction. Selleck Panobinostat In the CRPS cells, both the baseline calcium levels and the calcium transient
were reduced; however, the level of cell contraction was the same as that of the control cells, suggesting calcium-independent myofibril sensitization. The calcium effect was confirmed in patch-clamping experiments where calcium influx was reduced in the CRPS group compared to the control preparations. Eleven of 18 CRPS serum-IgG preparations induced functional or calcium abnormalities, while only one in 57 control preparations induced abnormalities (P < 0·0001). These results suggest that long-term CRPS is associated with specific anti-autonomic autoantibodies. Discussions in the field have traditionally assumed that although there might be an immune involvement in the initial CRPS stages the patients' pain would later be maintained by brain factors but, conversely, our results argue that there is an ongoing, potentially treatable immune abnormality. Additionally,
of the 11 serum-IgG preparations available from CRPS patients who participated in the previous IVIg treatment trial , all preparations from subjects who responded to IVIg treatment (n = 4) were active in the cardiomyocyte ID-8 assay, but the majority of preparations from non-responders to IgG (n = 4/7) were also active. This therefore indicates that CRPS-specific autoantibodies are not restricted to IVIg responders. The study group also investigated the effect of CRPS serum-IgG in a novel animal model via passive transfer . Serum-IgG preparations from 12 CRPS patients and 12 controls from the previous trial were administered to mice. Behaviour in the open field, stimulus-evoked pain and motor co-ordination were observed in order to ascertain whether the transfer of IgG antibodies produced signs of CRPS. Rearing behaviour was reduced significantly in the CRPS-IgG-treated group, and motor impairment was also observed; however, these mice were not suffering from CRPS, as assays for hyperalgesia revealed no results.