Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

Jami L. Saloman; Yan Li; Kimberly Stello; Wenhao Li; Shuang Li; Anna Evans Phillips; Kristen Hall; Evan L. Fogel; Santhi Swaroop Vege; Liang Li; Dana K. Andersen; William E. Fisher; Christopher E. Forsmark; Phil A. Hart; Stephen J. Pandol; Walter G. Park; Mark D. Topazian; Stephen K. Van Den Eeden; Jose Serrano; Darwin L. Conwell; Dhiraj Yadav

doi:10.1016/j.jpain.2023.07.006

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

Jami L. Saloman, Yan Li, Kimberly Stello, Wenhao Li, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L. Fogel, Santhi Swaroop Vege, Liang Li, Dana K. Andersen, William E. Fisher, Christopher E. Forsmark, Phil A. Hart, Stephen J. Pandol, Walter G. Park, Mark D. Topazian, Stephen K. Van Den Eeden, Jose Serrano, Darwin L. ConwellDhiraj Yadav

Research output: Contribution to journal › Article › peer-review

Abstract

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. Perspective: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

Original language	English
Journal	Journal of Pain
DOIs	https://doi.org/10.1016/j.jpain.2023.07.006
State	Accepted/In press - 2023

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute (NCI) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript.

Funding Information:
This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute ( NCI ) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript.

Publisher Copyright:
© 2023 United States Association for the Study of Pain, Inc.

Keywords

Glycoprotein 130
PROCEED Study
PROMIS-PQ
Platelet-derived growth factor B
Transforming growth factor beta 1

ASJC Scopus subject areas

Neurology
Clinical Neurology
Anesthesiology and Pain Medicine

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10.1016/j.jpain.2023.07.006

Cite this

Saloman, J. L., Li, Y., Stello, K., Li, W., Li, S., Phillips, A. E., Hall, K., Fogel, E. L., Vege, S. S., Li, L., Andersen, D. K., Fisher, W. E., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Topazian, M. D., Van Den Eeden, S. K., Serrano, J., ... Yadav, D. (Accepted/In press). Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis. Journal of Pain. https://doi.org/10.1016/j.jpain.2023.07.006

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title = "Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis",

abstract = "Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. Perspective: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.",

keywords = "Glycoprotein 130, PROCEED Study, PROMIS-PQ, Platelet-derived growth factor B, Transforming growth factor beta 1",

author = "Saloman, {Jami L.} and Yan Li and Kimberly Stello and Wenhao Li and Shuang Li and Phillips, {Anna Evans} and Kristen Hall and Fogel, {Evan L.} and Vege, {Santhi Swaroop} and Liang Li and Andersen, {Dana K.} and Fisher, {William E.} and Forsmark, {Christopher E.} and Hart, {Phil A.} and Pandol, {Stephen J.} and Park, {Walter G.} and Topazian, {Mark D.} and {Van Den Eeden}, {Stephen K.} and Jose Serrano and Conwell, {Darwin L.} and Dhiraj Yadav",

note = "Funding Information: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute (NCI) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript. Funding Information: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute ( NCI ) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript. Publisher Copyright: {\textcopyright} 2023 United States Association for the Study of Pain, Inc.",

year = "2023",

doi = "10.1016/j.jpain.2023.07.006",

language = "English",

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Saloman, JL, Li, Y, Stello, K, Li, W, Li, S, Phillips, AE, Hall, K, Fogel, EL, Vege, SS, Li, L, Andersen, DK, Fisher, WE, Forsmark, CE, Hart, PA, Pandol, SJ, Park, WG, Topazian, MD, Van Den Eeden, SK, Serrano, J, Conwell, DL & Yadav, D 2023, 'Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis', Journal of Pain. https://doi.org/10.1016/j.jpain.2023.07.006

TY - JOUR

T1 - Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

AU - Saloman, Jami L.

AU - Li, Yan

AU - Stello, Kimberly

AU - Li, Wenhao

AU - Li, Shuang

AU - Phillips, Anna Evans

AU - Hall, Kristen

AU - Fogel, Evan L.

AU - Vege, Santhi Swaroop

AU - Li, Liang

AU - Andersen, Dana K.

AU - Fisher, William E.

AU - Forsmark, Christopher E.

AU - Hart, Phil A.

AU - Pandol, Stephen J.

AU - Park, Walter G.

AU - Topazian, Mark D.

AU - Van Den Eeden, Stephen K.

AU - Serrano, Jose

AU - Conwell, Darwin L.

AU - Yadav, Dhiraj

N1 - Funding Information: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute (NCI) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript. Funding Information: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ): R21 DK122293 and K01 DK120737 (J.L.S.). The National Cancer Institute ( NCI ) and NIDDK for the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) under award numbers: U01DK108288 (Mayo Clinic), U01DK108300 (Stanford), U01DK108306 (University of Pittsburgh Medical Center), U01DK108314 (Cedars-Sinai Medical Center), U01DK108323 (Indiana University), U01DK108326 (Baylor College of Medicine), U01DK108327 (The Ohio State University), U01DK108332 (Kaiser Permanente), UO1DK108320 (University of Florida) and U01DK108328 (MD Anderson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest with any of the work presented in this manuscript. Publisher Copyright: © 2023 United States Association for the Study of Pain, Inc.

PY - 2023

Y1 - 2023

N2 - Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. Perspective: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

AB - Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. Perspective: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

KW - Glycoprotein 130

KW - PROCEED Study

KW - PROMIS-PQ

KW - Platelet-derived growth factor B

KW - Transforming growth factor beta 1

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UR - http://www.scopus.com/inward/citedby.url?scp=85168835220&partnerID=8YFLogxK

U2 - 10.1016/j.jpain.2023.07.006

DO - 10.1016/j.jpain.2023.07.006

M3 - Article

C2 - 37451493

AN - SCOPUS:85168835220

SN - 1526-5900

JO - Journal of Pain

JF - Journal of Pain

ER -

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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