PMID- 34602367
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20230707
IS  - 1424-3911 (Electronic)
IS  - 1424-3903 (Print)
IS  - 1424-3903 (Linking)
VI  - 21
IP  - 8
DP  - 2021 Dec
TI  - Serum biomarkers for chronic pancreatitis pain patterns.
PG  - 1411-1418
LID - S1424-3903(21)00580-9 [pii]
LID - 10.1016/j.pan.2021.09.016 [doi]
AB  - 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-1beta (IL-1beta), 
      interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFalpha), 
      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 TNFalpha and fractalkine. Patients with severe pain exhibited a 
      significant reduction in TNFalpha 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.
CI  - Copyright (c) 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.
FAU - Saloman, Jami L
AU  - Saloman JL
AD  - 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.
FAU - Tang, Gong
AU  - Tang G
AD  - Department of Biostatistics, Graduate School of Public Health, University of 
      Pittsburgh, Pittsburgh, PA, USA.
FAU - Stello, Kimberly M
AU  - Stello KM
AD  - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, 
      School of Medicine, University of Pittsburgh, PA, USA.
FAU - Hall, Kristen E
AU  - Hall KE
AD  - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, 
      School of Medicine, University of Pittsburgh, PA, USA.
FAU - Wang, Xianling
AU  - Wang X
AD  - Department of Biostatistics, Graduate School of Public Health, University of 
      Pittsburgh, Pittsburgh, PA, USA.
FAU - AlKaade, Samer
AU  - AlKaade S
AD  - Saint Louis University, Saint Louis, MO, USA.
FAU - Banks, Peter A
AU  - Banks PA
AD  - Brigham and Women's Hospital, Boston, MA, USA.
FAU - Brand, Randall E
AU  - Brand RE
AD  - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, 
      School of Medicine, University of Pittsburgh, PA, USA.
FAU - Conwell, Darwin L
AU  - Conwell DL
AD  - The Ohio State University Wexner Medical Center, Columbus, OH, USA.
FAU - Cote, Gregory A
AU  - Cote GA
AD  - Medical University of South Carolina, Charleston, SC, USA.
FAU - Forsmark, Christopher E
AU  - Forsmark CE
AD  - Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, 
      Gainesville, FL, USA.
FAU - Gardner, Timothy B
AU  - Gardner TB
AD  - Section of Gastroenterology and Hepatology, Geisel School of Medicine at 
      Dartmouth, Lebanon, NH, USA.
FAU - Gelrud, Andres
AU  - Gelrud A
AD  - Department of Internal Medicine, Miami Cancer Institute, Gastro Health, Miami, 
      FL, USA.
FAU - Lewis, Michele D
AU  - Lewis MD
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, 
      Jacksonville, FL, USA.
FAU - Sherman, Stuart
AU  - Sherman S
AD  - Indiana University School of Medicine, Indianapolis, IN, USA.
FAU - Slivka, Adam
AU  - Slivka A
AD  - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, 
      School of Medicine, University of Pittsburgh, PA, USA.
FAU - Whitcomb, David C
AU  - Whitcomb DC
AD  - 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.
FAU - Yadav, Dhiraj
AU  - Yadav D
AD  - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, 
      School of Medicine, University of Pittsburgh, PA, USA.
CN  - NAPS consortium
LA  - eng
GR  - R56 DK061451/DK/NIDDK NIH HHS/United States
GR  - R21 DK122293/DK/NIDDK NIH HHS/United States
GR  - K01 DK120737/DK/NIDDK NIH HHS/United States
GR  - U01 DK108306/DK/NIDDK NIH HHS/United States
GR  - R01 DK061451/DK/NIDDK NIH HHS/United States
GR  - R01 DK077906/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20210930
PL  - Switzerland
TA  - Pancreatology
JT  - Pancreatology : official journal of the International Association of 
      Pancreatology (IAP) ... [et al.]
JID - 100966936
RN  - 0 (Biomarkers)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Biomarkers/blood
MH  - Humans
MH  - *Interleukin-6
MH  - Pain
MH  - *Pancreatitis, Chronic/complications
MH  - Tumor Necrosis Factor-alpha
PMC - PMC8629935
MID - NIHMS1745371
OTO - NOTNLM
OT  - Chronic pancreatitis
OT  - Pain biomarkers
OT  - Pain frequency
OT  - Pain severity
OT  - Serum
COIS- Disclosures The authors have no disclosures and report no actual or potential 
      conflicts of interest.
EDAT- 2021/10/05 06:00
MHDA- 2022/03/01 06:00
PMCR- 2022/12/01
CRDT- 2021/10/04 05:40
PHST- 2021/06/08 00:00 [received]
PHST- 2021/09/15 00:00 [revised]
PHST- 2021/09/25 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2021/10/04 05:40 [entrez]
PHST- 2022/12/01 00:00 [pmc-release]
AID - S1424-3903(21)00580-9 [pii]
AID - 10.1016/j.pan.2021.09.016 [doi]
PST - ppublish
SO  - Pancreatology. 2021 Dec;21(8):1411-1418. doi: 10.1016/j.pan.2021.09.016. Epub 
      2021 Sep 30.