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Objectives and questions: Persistent postoperative pain affects a subset of patients undergoing total shoulder arthroplasty (TSA), even when objective clinical outcomes appear favorable. Understanding predictors of persistent pain could enhance patient selection, inform perioperative care, and guide the development of adjunctive therapies.

Material and methods: This prospective study included 106 patients undergoing primary TSA (mean age 70.9 ± 8.8 years; 52% female). Quantitative sensory testing (QST) was performed at baseline and follow-up time points up to 6 months postoperatively, including assessments of pain severity, pain interference, temporal summation using weighted pin probes applied to Digits II and III on both hands, and pressure pain thresholds (PPTs) using a digital algometer at the trapezius, deltoid and tibialis muscle on both the affected and non-affected sides. Intraoperatively, plasma samples were collected from four time points to analyze inflammatory markers, including interleukin-6 (IL-6) and others. Patients were stratified based on the presence or absence of persistent pain (NRS ≥3) at 3 months post-surgery.

Results: At 3 months postoperatively, 20 patients (19%) reported persistent pain (NRS ≥3). These patients showed altered QST profiles, including lower pressure pain thresholds and greater temporal summation, particularly on the non-affected side, suggesting central sensitization. Overall, temporal summation was comparable between groups. However, patients with persistent pain demonstrated significantly greater temporal summation using the 128 mN pinprick on the non-affected side at Digit III (Mann–Whitney U test, p = 0.041). At baseline, PPTs differed significantly between groups, with lower thresholds in participants reporting persistent pain across the trapezius, deltoid, and tibialis muscles on both affected and non-affected sides (Mann–Whitney U tests, p < 0.05). At 3 months, these differences remained significant at the trapezius and tibialis muscles bilaterally (Mann–Whitney U tests, p ≤ 0.028), whereas no significant group difference was observed at the deltoid muscle on the non-affected side (p = 0.074). Notably, elevated intraoperative IL-6 levels were correlated with persistent pain at follow-up. Patients with higher inflammatory marker levels intraoperatively also showed reduced improvements in pain interference and greater residual pain severity.

Discussion and conclusions: QST combined with intraoperative inflammatory biomarkers such as IL-6 may help identify patients at risk for persistent pain following TSA. These findings support the potential for targeted perioperative interventions such as corticosteroids (e.g., dexamethasone) to modulate inflammatory responses and improve postoperative pain outcomes. Integrating sensory profiling and biomarker analysis into clinical pathways may enhance personalized pain management and reduce the burden of chronic postsurgical pain.