Development of Validated Method to Assess, Characterize Pain Mechanisms in Chronic Pancreatitis

A validated, clinically feasible method developed to assess and characterize the mechanisms causing pain in patients with chronic pancreatitis (CP) can be a viable tool to evaluate and inform pain management in these patients, according to research published in Pancreatology.

Abdominal pain in CP is generally debilitating, and patients who have constant pain have been found to have lower quality of life, greater rates of disability, and higher resource utilization regardless of the intensity of their pain.

Researchers conducted a cross-sectional, multicenter study to validate this clinically feasible method, which is based on quantitative sensory testing (QST). In total, 60 patients with chronic CP and 122 control patients were recruited from international pancreas centers in Pennsylvania, Maryland and Denmark. All participants were 18 years of age or older, and control patients had no pancreatic disease or abdominal pain.

All but 1 control patient underwent standardized testing for all P-QST parameters, including cold pressor, conditioned pain modulation paradigm, repetitive pin-prick, and pressure stimulation of upper abdomen (pancreatic area) and control areas. The resultant absolute, site (dermatome) specific pressure thresholds were stratified by stimulation site, age, and gender. Women were significantly more sensitive to pressure stimulation compared with all men, and older participants were less sensitive to pressure stimulation compared with younger participants. Investigators also found that the pressure sum scores for all stimulation sites were influenced by gender; lower thresholds were observed for women, with an effect size of 690 kPa for the pressure pain detection threshold (pPDT) sum score and 1194 kPa for kPa for the pressure pain tolerance threshold (pPTT) sum score.

Both the pPDT and pPTT indices and pPDT and pPTT sums were “strongly correlated,” reflecting potentially redundant information. Therefore, the investigators chose to rely on parameters based on pPDT, as it is based on pain thresholds “that are more intuitive and easier to explain to patients.”

Patients with CP had a mean age of 54.6±11.8 years; 65% were men and 66% had CP with a toxic (alcoholic and/or smoking) etiology. 55% of patients used opioids, and 45% used ≥1 adjuvant analgesics.

The researchers identified 3 distinct phenotypes of central pain processing: widespread sensitization, segmental sensitization, and normal central pain processing. Quantile regression analysis was used to develop 3 algorithms (5/95, 10/90, and 25/75). The analysis using 25/75 percentiles demonstrated significant differences in the distribution of P-QST phenotypes between patients with CP and the controls, although a high degree of overlap was noted between subgroups, specifically the subgroup demonstrating segmental sensitization. Algorithms based on the 10/90 and 5/95 percentiles demonstrated good separation between patients with CP and the controls for both the segmental and widespread sensitization subgroups. The researchers proposed utilizing the algorithm based on the 10/90 percentile to clinically diagnose abnormal central pain processing in patients with CP.

Study limitations included variability in dynamic QST testing, the need to further refine criteria for derived normative thresholds, and the overall generalizability to real-life clinical populations. Future studies should also include larger sample sizes.

“[T]he presented method showed great promise in its ability to differentiate phenotypes of central pain processing by providing reliable indicators of nociceptive changes including evidence of segmental and widespread sensitization of central nociceptive pathways,” the researchers concluded. “These pain phenotypes can be used in the future to attempt prediction of response to treatment in patients with painful [chronic pancreatitis] and thus provides a framework for personalized pain management.”

Reference

Phillips AE, Faghih M, Kuhlmann L, et al; on behalf of the Pancreatic Quantitative Sensory Testing (P-QST) Working Group. A clinically feasible method for the assessment and characterization of pain in patients with chronic pancreatitis [published online November 20, 2019]. Pancreatology. doi: 10.1016/j.pan.2019.11.007