title: A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.
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 8days. 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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624 Pécs, Szigeti u. 12., Hungary János Szentágothai Research Centre, University of Pécs, H-7634 Pécs, Ifjúság u. 34., Hungary PharmInVivo Ltd., H-7629 Pécs, Szondi György u. 10., Hungary Department of Translational Medicine, University of Liverpool, Liverpool, UK The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: Valéria
authors.initials: V
authors.lastname: Tékus
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Hajna
authors.forename: Éva
authors.initials: É
authors.lastname: Borbély
authors.forename: Adrienn
authors.initials: A
authors.lastname: Markovics
authors.forename: Teréz
authors.initials: T
authors.lastname: Bagoly
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.forename: Victoria
authors.initials: V
authors.lastname: Thompson
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kemény
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.forename: Andreas
authors.initials: A
authors.lastname: Goebel
mesh_terms: D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D020918:Complex Regional Pain Syndromes / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000633:toxicity*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D010865:Pilot Projects
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G
keywords: Autoantibody; Autoimmunity; CRPS; Complex regional pain syndrome; Pain