THU0557 NERVE GROWTH FACTOR, SCLEROSTIN AND DKK-1 SERUM LEVELS IN COMPLEX REGIONAL PAIN SYNDROME1 (CRPS-1): A PILOT STUDY ON 41 PATIENTS

Background: Pain is the hallmark of Complex Regional Pain Syndrome (CRPS). Nerve growth factor (NGF), widely known as pain mediator, is increased in the affected skin 1 and in tibia bone of rat models of CRPS, while is lowered by administration of anti-NGF antibodies 2 . CRPS usually develops after limb trauma, most frequently a fracture 3 . Some reports considered bone as a main player in CRPS pathogenesis, hypnotizing that sclerostin (SOST) 4 and Dickkopf-related protein-1 (DKK-1) may be involved in CRPS pathogenesis. Objectives: To evaluate NGF, SOST, and DKK-1 serum levels from affected arm of CRPS patients and compare them with unaffected one and healthy controls (HCs). Methods: Adults patients affected by CRPS diagnosed according to IASP criteria at upper limb were consecutively enrolled from April 2017 to August 2018. Patients with prior treatment with bisphosphonates, and history of disorders of mineral metabolism were excluded. Sera from the basilica vein of affected and unaffected arm of CRPS patients were collected, as well as sera from HCs paired for age and sex. NGF, SOST, and DKK-1 concentrations were determined by ELISA kit. Comparisons between patients and HCs were performed by Student test, while comparison between affected and unaffected arms were performed with Wilcoxon test for paired data. Pearson correlation was used to correlate NGF, SOST, and DKK-1 levels with demographic and clinical variables. Results: The overall population included 41 patients: males (M) 21.9%, mean age at diagnosis [± standard deviation, SD] 61.9±8.4 yrs, median disease duration 67 days (inter quartile range (IQR) 14.0; 22.5), 39 (95.2%) experienced a fracture as inciting event, mean VAS pain score (0-100) 54.8±18.6 mm. Mean NGF levels (pg/mL) were 12.0±28.8 and 11.4±35.5 in the affected and unaffected side, respectively, and 13.5±55.0 in HCs. NGF was undetectable in most patients; no statistical significant differences of NGF levels were found between patients and HCs. Mean SOST levels (pmol/L) were 32.6±16.1, 29.8±17.7, and 34.0±13.3 in affected, unaffected arm, and in HCs, respectively. No statistical significantly differences of SOST levels were found between patients and HCs, while a significant difference was found between affected and unaffected arms (p=0.03). Mean DKK-1 levels (pmol/L) were higher in affected arm (31.2±29.5) than in unaffected one (29.3±28.6) or in HCs (27.5±18.2) without reaching statistical significance. NGF was significantly correlated with VAS pain score (p=0.04). Conclusion: To our best knowledge, this is the first study to evaluate NGF, SOST, and DKK-1 levels in adults affected by CRPS-1. SOST levels were significantly higher in affected arms compared to unaffected ones, suggesting a possible role of this bone mediator in CRPS pathogenesis. NGF was consistent with the expression of pain, trough VAS pain score. Further studies need to clarify these preliminary findings. References: [1] Li WW, et al. Pain2010; 151:843–52. [2] Sabsovitch I, et al. Pain2008; 138: 47–60. [3] de Mos M, et al. Pain2007; 129:12-20. [4] Robling AG, et al. J Biol Chem2008;283:5866-75. Disclosure of Interests: Chiara Crotti: None declared, Maria Manara: None declared, Francesca Zucchi: None declared, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Maurizio Rossini: None declared, Massimo Varenna: None declared