Background & Aims
Despite high incidence of pain chronification after combined trauma and surgery, the underlying mechanisms of chronic posttraumatic and/or postsurgical pain (CPSP) after fracture-related surgery are still poorly understood. Bone surgery often leads to CPSP 1. Despite the multifactorial etiology of CPSP, this high incidence reveals specific underlying mechanisms possibly attributable to osseous involvement. Although there is evidence for an inflammatory response in CPSP2, studies investigating these processes are lacking3, especially after trauma and surgery. Consequently, prospective longitudinal serum profiling of various cytokines, chemokines and adipocytokines as potential biomarkers in patients with and without CPSP after traumatic fracture requiring osteosynthesis was conducted on the first day (D1), at week six (W6) and one year after surgery (Y1), comparing patients with CPSP after one year to those without.
Methods
All patients (N=30) included in this analysis were obtained from the CHRONPOST study1. Blood was taken on the first day (D1), at week six and one year (Y1) after surgery. CPSP was defined as pain intensity of NRS ?3 during movement at Y1 located at the initial surgical site .Serum protein concentrations of cytokines were analyzed using Multiplex Assays (Luminex Technology, 22 cytokines). For analysis and comparison of cytokines over time, a mixed effect model with repeated measures was applied. Two-way Spearman correlations were applied for correlation of pain intensity and cytokine levels Receiver operating characteristic (ROC) curves were calculated for patients with CPSP compared to patients without CPSP.
Results
After one year, 40% (N=12/30) of the patients had developed CPSP reporting a pain intensity during movement of 5.5±1.8 NRS and 75% reporting at least one neuropathic symptom. Out of multiple cytokine analysis the cytokine profiles of Patients with CPSP showed higher levels of Adiponectin and Resistin already at six weeks (W6) up to one year (Y1) after surgery compared to patients without (n=18). Interestingly, higher CCL5 (C-C motif chemokine Ligand-5 (Rantes), Chemokin ) levels immediately after surgery predicted the development of CPSP. Moreover, Adiponectin and CCL5 levels at W6 and Y1 significantly correlated with pain intensity in patients with CPSP. Additionally, Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Resistin levels correlated with overall pain intensity.
Conclusions
Our cytokine analysis uncovered an imbalance of serum cytokines and chemokines during the chronification process in patients who developed CPSP after surgically treated fractures over a one year period. Elevated CCL5 levels immediately after surgery may trigger CPP and predict its development. Especially Adiponectin and resistin are revealed as novel biomarkers in CPSP for initiation and persistence of CPSP. As these cytokines are expressed and secreted by osteoblasts, a hitherto unexplored crosstalk between pain and bone regeneration after surgery remains to be further analysed. Our data hints towards an increased secretion and exhaustion of cytokine response already after trauma in parallel with the acute onset of pain corroborates the notion that the (bone) damage leading to CPSP might be more likely associated with a posttraumatic rather than a postsurgical origin. Our data opens new avenues for translational research.
References
1. Aulenkamp JL, Malewicz NM, Brauckhoff JD, Zahn PK, Ebel M, Schnitzler R, Clever J, Geßmann J, Bauer M, Meyer-Frießem CH. Chronic Pain Following Fracture-Related Surgery: Posttraumatic Rather Than Postsurgical Origin Promotes Chronification-A Prospective Observational Study With 1-Year Follow-up. Anesth Analg. 2022 May 1;134(5):974-986. doi: 10.1213/ANE.0000000000005807. PMID: 34889805.
2. Sluka, Kathleen A.a, Wager, Tor D.b; Sutherland, Stephani P.c; Labosky, Patricia A.d; Balach, Tessae; Bayman, Emine O.f; Berardi, Giovannia; Brummett, Chad M.g; Burns, Johnh; Buvanendran, Asokumari; Caffo, Brianc; Calhoun, Vince D.j; Clauw, Danielg; Cha ZJ the AC. Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures. Pain 2023.
3. Pogatzki-Zahn EM, Segelcke D. Searching for the rainbow: biomarkers relevant for chronic postsurgical pain. Pain 2023.
Presenting Author
Jana Aulenkamp
Poster Authors
Nathalie Malewicz-Oeck
M.D.; MSc
Department of Anaesthesiology, Intensive Care Medicine and Pain Management, BG University Hospital B
Lead Author
Jana Luisa Aulenkamp
M.D.
Clinic for Anesthesiology and Intensive Care, University Hospital Essen, Germany
Lead Author
Sebastian Oeck
PhD
Lead Author
Peter Konrad Zahn
M.D.
Department of Anaesthesiology, Intensive Care Medicine and Pain Management, BG University Hospital B
Lead Author
Claudia Scheffzuek
M.D.
Department of Anaesthesiology, Intensive Care Medicine and Pain Management, BG University Hospital B
Lead Author
Christine Hildegard Meyer-Frießem
M.D.
Department of Anaesthesiology , Intensive Care Medicine and Pain Management, BG University Hospital
Lead Author
Topics
- Assessment and Diagnosis