EarLy idEntification of chroniC posT-suRgical pAin patients by immunophenotyping (ELECTRA) – is such a study feasible (ELECTRA-F)?

• Applicants: Professor Dr. Frank Birklein; Professor Dr. Stefan Bittner; Professorin Dr. Heike Lydia Rittner
• Subject Area: Anaesthesiology ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559983009

Chronic posttraumatic limb pain and complex regional pain syndrome (CPTLP/CRPS) is a complication that is often diagnosed with a delay of several months. Once CPTLP/CRPS is established it often leads to persistent severe pain and livelong disability. We hypothesize that the evidence of an immune-driven pathophysiology of CRPS and of a proposed role of myeloid cells now offers the opportunity for a better stratification of "patients at risk" by performing immunophenotyping shortly after the trauma. This will be investigated in EarLy idEntification of chroniC posTsuRgical pAin by immunophenotyping (ELECTRA). Patients could then be treated by immunotherapy before CPTLP/CRPS develops (ELECTRA-T). However, CPTLP/CRPS is not common, predictive parameters need to be validated, and immunophenotyping is time sensitive and expensive. Thus, a strategy for identification of "patients at risk" for CPTLP/CRPS shortly after limb trauma is mandatory, and immunophenotyping protocols have to be optimized for a multicenter design (frozen white blood cells and sequencing approaches). Here we apply for the feasibility study ELECTRA-F, which will not only provide new important insights into the pathophysiology of CRPS, but it will also refine the logistics needed to prepare ELECTRA and ELECTRA-T. Based on the evidence that severe pain about one week after conservatively treated radial fractures increases the probability of CPTLP/CRPS 15-30 fold, we will use in the first work package postsurgical pain as the selection criterium to establish the logistics for screening and recruitment. We postulate that we thereby enrich for "risk patients". In the second work package, we will optimize protocols for individual immunophenotyping from blood of stored/frozen WBCs (scRNA seq, T cell receptor sequencing) and conduct first analyses. Third, we investigate the role of the immune system and autoreactivity using serum samples from our previous collaborative investigations. ELECTRA-F will thus provide the basis for a reliable sample size calculation for the successful implementation of the prospective large scale in-depth diagnostic study (ELECTRA) to identify "at-risk" patients for CPTLP/CRPS and to prepare a randomized controlled treatment trial (ELECTRA-T) to prevent CPTLP/CRPS. In addition, we will ultimately gain a better understanding of the pathophysiology regarding pathways of immune dysfunction, allowing for better treatment selection.

• DFG Programme: Research Grants