BACKGROUND AND AIMS:Pain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST). METHODS:This was a cross-sectional, multicenter study of 122 control subjects without pancreatic disease and another 60 patients with painful CP. All subjects underwent standardized QST assessments including a cold pressor test, a conditioned pain modulation paradigm, repetitive pin-prick stimuli (temporal summation) and pressure stimulation of the upper abdominal (pancreatic) and control dermatomes. The effects of age and gender on QST assessment parameters were investigated and normative reference values based on quartile regression were derived and implemented in algorithms to categorize patients according to their patterns of central pain processing (normal vs. segmental sensitization vs. widespread sensitization). RESULTS:Absolute pressure thresholds were subject to clinically relevant gender effects (all p < 0.001), while the remainder of QST parameters were unaffected by age and gender. The algorithm with the best discriminatory capacity showed good separation between patients and controls (p < 0.001); 50% of patients had normal central pain processing, 23% had evidence of segmental sensitization and 27% had evidence of widespread sensitization. CONCLUSION:We show normative reference values for a clinically feasible method for assessment and characterization of pain mechanisms in patients with CP. Application of this method streamlines the evaluation of pancreatic pain and may be used to inform treatment. CLINICALTRIALS. GOV ID:NCT03434392.

INTRODUCTION: Pain is a common problem in patients with chronic pancreatitis (CP) and effective therapy remains a considerable challenge. Methods based on quantitative sensory testing (QST) provide information on pain modulation and have demonstrated promise in predicting future pain status and the efficacy of analgesics. The aims of this study were to evaluate the existence of CP subgroups with different pain modulatory phenotypes and to investigate associations with patients' clinical pain and psychological profiles. METHODS: This was a cross-sectional, multicentre study of CP outpatients. Patients fulfilled a number of questionaries' including the Brief Pain Inventory short form, the Hospital Anxiety and Depression Score as well as measures of Conditional and Situational Pain Catastrophising. Using a standardized QST protocol, we recorded pain detection thresholds (PDTs) to static muscle pressure stimulations at the “pancreatic dermatomes” on the upper abdomen and back and at three control areas. The ratio between pancreatic and control PDTs were calculated (PDT-index) to offset interindividual differences in absolute thresholds. The PDT-index was used in conjunction with repetitive pinprick stimulations (temporal summation) applied at the abdominal pancreatic dermatome to obtain a measure of segmental hyperalgesia. A conditioned pain modulation (CPM) paradigm was performed to investigate descending pain modulation. Patients were grouped based on normative QST reference values and questionnaire scores were compared across subgroups to investigate associations between patients' pain modulatory phenotypes and clinical pain and psychological profiles. RESULTS: A total of 91 patients were enrolled in the study. The mean age was 53.1 ± 12.7 y, 62% were men, and 65% had toxic etiology. Three distinct pain modulatory phenotypes were found: group 1 (n = 31) had normal pain modulation; group 2 (n = 17) had segmental sensitization; group 3 (n = 43) had widespread sensitization. Patients with widespread sensitization had higher pain score ( P < 0.01) and lower QOL ( P < 0.05) in comparison to segmental and normal. In contrast, psychological features were comparable across subgroups. CONCLUSION: CP patients with widespread sensitization have significantly higher levels of pain and lower QOL. QST characterizes the sensory profiles independently of the patient's psychological status and provides an unbiased proxy of pain processing. This information can be used for prognostication and tailoring of management strategies.

Objectives Presentation of pancreatic adenocarcinoma (PC) as acute pancreatitis (AP), association of chronic pancreatitis (CP) with PC, and role of inflammation in PC carcinogenesis are well recognized. We hypothesized that inflammatory changes associated with remote history of AP (≥2 years before PC diagnosis) would result in earlier age of PC diagnosis. Methods We evaluated PC patients prospectively enrolled in the Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study at the University of Pittsburgh for history of pancreatitis and reviewed relevant medical records and imaging studies. Univariate and multivariable linear regression analyses evaluated the relationship between PC and remote history of AP. Results Among 790 patients with histologically confirmed PC, 114 (14.4%) had a history of pancreatitis (AP within 2 years of PC diagnosis in 69 [8.7%], remote history of AP in 28 [3.5%], CP in 4 [0.5%], and unknown duration of pancreatitis in 13 [1.6%]). After controlling for age, sex, body mass index, smoking, alcohol history, and diabetic status at diagnosis, patients with a remote history of AP were diagnosed on average 4.7 years earlier with PC when compared with PC patients without history of AP (P < 0.035). Conclusions Remote history of AP may accelerate carcinogenesis in PC.