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A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome

Tékus, Valériaa,b,1; Hajna, Zsófiaa,b,1; Borbély, Évaa,b; Markovics, Adrienna,b; Bagoly, Teréza,b; Szolcsányi, Jánosa,b,c; Thompson, Victoriad; Kemény, Ágnesa,b; Helyes, Zsuzsannaa,b,c,1; Goebel, Andreasd,e,*,1

doi: 10.1016/j.pain.2013.10.011
Article

Summary The transfer of serum IgG from patients with long-standing complex regional pain syndrome (CRPS) to mice, followed by mild hind paw trauma, causes typical signs of CRPS.

ABSTRACT The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8 days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.

a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624 Pécs, Szigeti u. 12., Hungary

b János Szentágothai Research Centre, University of Pécs, H-7634 Pécs, Ifjúság u. 34., Hungary

c PharmInVivo Ltd., H-7629 Pécs, Szondi György u. 10., Hungary

d Department of Translational Medicine, University of Liverpool, Liverpool, UK

e The Walton Centre NHS Foundation Trust, Liverpool, UK

* Corresponding author at: Pain Research Institute, Department of Translational Medicine, University of Liverpool, Liverpool L7 7AL, UK. Tel.: +44 151 529 5820; fax: +44 151 529 5821.

E-mail address: andreasgoebel@rocketmail.com

1 Valéria Tékus and Zsófia Hajna made equal contributions to this work and, similarly, Zsuzsanna Helyes and Andreas Goebel contributed equally to this paper.

Article history:

Received 15 August 2013

Received in revised form 11 October 2013

Accepted 14 October 2013

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

© 2014 International Association for the Study of Pain
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