Sensory alterations and immunological changes during the chronification of postsurgical pain: a study protocol for a prospective observational cohort study

Introduction: Chronic postsurgical pain (CPSP) represents a widely underdiagnosed and often poorly treated medical problem, affecting 10-50% of all surgical patients, exhibiting neuropathic features in 35-60%. It is hypothesised that surgery-induced tissue damage and the subsequent immune response cause sensory alterations in the early postoperative period, ultimately leading to a chronic neuropathic or nociplastic pain state. The 'Sensory Changes and Immunological parameters in Postsurgical pain' study (SCIP-Pain study) was designed to test this hypothesis and identify sensory alterations and changes in the immunological response that are related to the development of CPSP with neuropathic features.

Methods and analysis: This protocol describes the SCIP-Pain study-an ongoing prospective observational cohort study involving 150 adult patients undergoing elective lower extremity orthopaedic surgery. Study participants complete questionnaires, undergo quantitative sensory testing (QST) and provide blood samples to assess the immunological response at various time points: before surgery, 2 weeks and 3 months after surgery. To reduce dimensionality, cluster analyses will be conducted on QST and immunological parameters. Cluster allocation, along with other preselected candidate predictors, will subsequently be used in a generalised mixed-effects model to predict CPSP with neuropathic features within 3 months after surgery as the primary outcome.

Ethics and dissemination: This study received approval from the Medical Ethics Committee NedMec (protocol NL77085.041.21), as well as from all participating centres. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences.