Marie-Theres Kassik, Mahya Faghih, Conrad Bandhauer, Josefine Jäger, Sophie Rauschenberg, Søren S Olesen, Daniel A Laheru, Lei Zheng, Anna E Phillips, Dhiraj Yadav, Jonas Rosendahl, Vikesh K Singh, Asbjørn M Drewes, Marko Damm
Although altered pain processing was frequent in painful PDAC, its association with patient-reported outcomes differed from that observed in CP. In particular, hyperalgesia showed a disease-specific relationship with pain-related functional impairment. These findings suggest that the clinical meaning of P-QST-defined hyperalgesia in PDAC cannot simply be inferred from CP and support further PDAC-specific studies linking pain phenotype to patient-reported burden and treatment response and pain management approaches might not be transferable across diseases.
INTRODUCTION: Abnormal pain processing has been associated with impaired patient-reported outcomes (PROMs) in chronic pancreatitis (CP), but its clinical relevance in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We investigated the association between P-QST-defined hyperalgesia and pain-related, psychological, and quality-of-life outcomes in patients with painful PDAC and compared these associations with CP.
METHODS: This multicenter cross-sectional analysis included patients with painful CP and PDAC at five tertiary referral hospitals in Denmark, Germany and the USA. Based on the results of pancreatic quantitative sensory testing (P-QST), patients were classified into three subgroups according to hyperalgesia status: no hyperalgesia, reflecting normal pain processing; segmental hyperalgesia at the pancreatic dermatome, suggesting abnormal spinal pain processing; widespread hyperalgesia, indicative of pathological pain processing across the entire neuraxis. PROMs included the Brief Pain Inventory (BPI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and EORTC QLQ-C30. Between-disease P-QST analyses were adjusted for age, sex, and regular opioid use. Exploratory disease-by-hyperalgesia interaction analyses assessed whether associations between hyperalgesia and selected PROMs differed between CP and PDAC.
RESULTS: A total of 275 patients (153 CP, 122 PDAC) were enrolled. Hyperalgesia was present in 53.6% of patients with CP and 43.8% of patients with PDAC, with no statistically significant difference after multivariable adjustment (aOR 0.75, 95% CI 0.43-1.33; p = 0.327). Patients with CP reported greater pain intensity (p = 0.027), pain interference (p = 0.049), and pain catastrophizing (p = 0.034) than patients with PDAC. Within the PDAC cohort, hyperalgesia was not associated with consistent differences in pain intensity, pain interference, catastrophizing, anxiety, or quality-of-life outcomes. However, formal interaction analysis demonstrated that the association between hyperalgesia and BPI pain interference differed between PDAC and CP (interaction β=1.61, 95% CI 0.27-2.95; p = 0.018).
CONCLUSION: Although altered pain processing was frequent in painful PDAC, its association with patient-reported outcomes differed from that observed in CP. In particular, hyperalgesia showed a disease-specific relationship with pain-related functional impairment. These findings suggest that the clinical meaning of P-QST-defined hyperalgesia in PDAC cannot simply be inferred from CP and support further PDAC-specific studies linking pain phenotype to patient-reported burden and treatment response and pain management approaches might not be transferable across diseases.