Jami L Saloman1, Gong Tang2, Kimberly M Stello3, Kristen E Hall3, Xianling Wang2, Samer AlKaade4, Peter A Banks5, Randall E Brand3, Darwin L Conwell6, Gregory A Coté7, Christopher E Forsmark8, Timothy B Gardner9, Andres Gelrud10, Michele D Lewis11, Stuart Sherman12, Adam Slivka3, David C Whitcomb13, Dhiraj Yadav3. 1. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA; Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, PA, USA; Department of Neurobiology, School of Medicine, University of Pittsburgh, PA, USA. Electronic address: jls354@pitt.edu. 2. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 3. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA. 4. Saint Louis University, Saint Louis, MO, USA. 5. Brigham and Women's Hospital, Boston, MA, USA. 6. The Ohio State University Wexner Medical Center, Columbus, OH, USA. 7. Medical University of South Carolina, Charleston, SC, USA. 8. Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA. 9. Section of Gastroenterology and Hepatology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 10. Department of Internal Medicine, Miami Cancer Institute, Gastro Health, Miami, FL, USA. 11. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA. 12. Indiana University School of Medicine, Indianapolis, IN, USA. 13. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA; Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, PA, USA; Departments of Cell Biology & Physiology, and Human Genetics, University of Pittsburgh, PA, USA.
Abstract
OBJECTIVES: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. DISCUSSION: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.
OBJECTIVES: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. DISCUSSION: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.
Authors: Søren S Olesen; Louise Kuhlmann; Srdan Novovic; Camilla Nøjgaard; Evangelos Kalaitzakis; Nanna M Jensen; Trond Engjom; Georg Dimcevski; Anne Waage; Stephan L Haas; Miroslav Vujasinovic; Romualdas Riauka; Aldis Pukitis; Imanta Ozola-Zālīte; Alexey Okhlobystin; Mikael Parhiala; Johanna Laukkarinen; Asbjørn M Drewes Journal: J Gastroenterol Hepatol Date: 2019-07-17 Impact factor: 4.029
Authors: C Mel Wilcox; Bimaljit S Sandhu; Vikesh Singh; Andres Gelrud; Judah N Abberbock; Stuart Sherman; Gregory A Cote; Samer Al-Kaade; Michelle A Anderson; Timothy B Gardner; Michele D Lewis; Christopher E Forsmark; Nalini M Guda; Joseph Romagnuolo; John Baillie; Stephen T Amann; Thiruvengadam Muniraj; Gong Tang; Darwin L Conwell; Peter A Banks; Randall E Brand; Adam Slivka; David Whitcomb; Dhiraj Yadav Journal: Am J Gastroenterol Date: 2016-08-16 Impact factor: 10.864
Authors: Stuart M Robinson; Sebastian Rasch; Sebastian Beer; Irena Valantiene; Artautas Mickevicius; Elisabeth Schlaipfer; Jelena Mann; Patrick Maisonneuve; Richard M Charnley; Jonas Rosendahl Journal: Sci Rep Date: 2019-05-13 Impact factor: 4.379