BIOCHEMICAL PROFILES OF PATIENTS WITH CHRONIC PANCREATITIS AND CENTRAL SENSITIZATION

Background Chronic pancreatitis (CP) may severely impact quality of life (QoL). Since CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact on patients. Such studies are currently lacking. Therefore, the aim of the present study is to gain insight into the course and predictors of both physical and mental QoL in patients with CP using prospective longitudinal data from a large cohort of patients.
Methods Post-hoc analysis of patients with CP registered in a prospective database between 2011 and 2019. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function and pancreatic interventions were assessed from patients’ medical records and through standard follow-up questionnaires. The physical (PCS) and mental component summary (MCS) scales of the Short-Form 36 were used to assess QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models (GLMM).
Results Overall, 1,165 patients with CP were included for this analysis. During 10-year follow-up, GLMM analyses revealed improvements in both PCS (41.6 to 45.1, p < .001) and MCS (45.8 to 48.5, P = 0.041). Older age, no alcohol consumption, unemployment, need for dietetic consultation, steatorrhea, higher Izbicki pain score and pain coping mechanism were negatively associated with physical QoL (P < .05). For mental QoL, a positive correlation was found between employment, non-alcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient.
Conclusions The present study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL in patients with CP are nutritional status, exocrine pancreatic function, employment status, and patients’ coping strategy.

Background: Central sensitization is a dimension of the pain experience in patients with painful chronic pancreatitis (CP) that has been identified by detection of specific patterns of hyperalgesia via pancreatic quantitative sensory testing (P-QST). Patients with hyperalgesia respond poorly to conventional therapy. Currently, there are no mechanism-based biomarker signatures for central sensitization. This pilot study hypothesized that specific biomarker profiles will associate with the presence of hyperalgesia in patients with painful CP.

Methods: Biomarkers (cytokines, chemokines, peptides, hormones) potentially associated with inflammation and metabolism were measured (all pg/mL) in serum samples from CP patients enrolled in the P-QST study. P-QST was used to classify patients based on the presence of hyperalgesia. Biomarker levels are reported as median and interquartile range. In cases where levels were below the level of detection (LOD), a binary variable (detectable v non-detectable) was created. P-values were calculated in the univariable analysis using the Wilcoxon rank-sum test, and Benjamini & Hochberg method for control of false discovery rate (FDR) was applied. Machine learning techniques including random forests and principal component analysis (PCA) were utilized to identify biomarker patterns (individual or groups) that correlate with presence of hyperalgesia.

Results: Of 39 patients, 22 (56%) had hyperalgesia on P-QST testing. Patients with hyperalgesia had significantly lower levels of Tumor Necrosis Factor-alpha (TNF-α) (1.6 [1.4: 2.4] v 3.2 [2.7: 4.9]; p = 0.0003), interleukin (IL) -17F (55.3 [0.0: 133.3] v 94.2 [54.9: 188.8]; p = 0.035), ghrelin (94.3 [34.4: 140.5] v 140.6 [121.4: 226.4]; p = 0.018), and IL - 27 (115.1 [80.5: 195.7] v 176.3 [114.4: 289.0]; p = 0.042). Using FDR-adjusted p-values, lower TNF-α was significantly associated with presence of hyperalgesia (p<0.01) and ghrelin was marginally significant (p=0.09). On random forests analysis, 56% of patients had TNF-α level <2.5, of those 86% had hyperalgesia; whereas among the 44% of patients whose TNF-α was ≥ 2.5, only 18% had hyperalgesia. On PCA analysis, 3 principal components were able to identify patients with hyperalgesia in increasingly higher proportions.

Conclusions: This pilot study suggests that distinct biochemical profiles may associate with presence of hyperalgesia in CP patients. Several cytokines and hormones with anti-nociceptive properties were higher in subjects that did not have hyperalgesia. Validation in larger populations and further work combining biomarker data with clinical characteristics will help in the development of precision medicine tools to optimize treatments for painful CP.