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Papers of the Week

Papers: 11 May 2019 - 17 May 2019

Human Studies

2019 Oct




What is normal trauma healing, what is Complex Regional Pain Syndrome I? An analysis of clinical and experimental biomarkers.


Dietz C, Müller M, Reinhold A-K, Karch L, Schwab B, Forer L, Vlckova E, Brede E-M, Jakubietz R, Üçeyler N, Meffert R, Bednarik J, Kress M, Sommer C, Dimova V, Birklein F, Rittner HL
Pain. 2019 Oct; 160(10):2278-2289.
PMID: 31095096.


Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison to healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patients reported outcomes (PRO) and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FC) not fulfilling the CRPS diagnostic criteria. We included upper extremity FCs, acute CRPS I patients within one year after trauma, a second disease control group (painful diabetic polyneuropathy, pDN) and healthy controls. FCs were not symptoms-free, but reported some pain, disability, anxiety and cold pain hyperalgesia in quantitative sensory testing (QST). CRPS patients had higher scores for pain, disability and all PROs. In QST, ipsi- and contralateral side differed significantly. However, on the affected side CRPS patients were more sensitive in only three parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors which distinguish CRPS and FC. FC as a control group can assist to discover resolution factors after trauma.