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Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors

Dubuis, E, Thompson, V, Leite, MI, Blaes, F, Maihöfner, C, Greensmith, DJ, Vincent, A, Shenker, N, Kuttikat, A, Leuwer, M and Goebel, A 2014, 'Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors' , Pain, 155 (11) , pp. 2408-2417.

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Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P<0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with α-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the α-1a receptor, CRPS-IgG was applied to α-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to α-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.

Item Type: Article
Themes: Health and Wellbeing
Subjects outside of the University Themes
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Pain
Publisher: Elsevier
Refereed: Yes
ISSN: 1872-6623
Related URLs:
Funders: Pain Relief Foundation, National Institute for Health Research, CSL-Behring, Switzerland
Depositing User: D Greensmith
Date Deposited: 21 Jan 2015 11:45
Last Modified: 23 Jan 2015 09:58

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