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Observational Study
. 2023 Dec;24(12):2199-2210.
doi: 10.1016/j.jpain.2023.07.006. Epub 2023 Jul 13.

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

Jami L Saloman  1 , Yan Li  2 , Kimberly Stello  3 , Wenhao Li  2 , Shuang Li  2 , Anna Evans Phillips  3 , Kristen Hall  3 , Evan L Fogel  4 , Santhi Swaroop Vege  5 , Liang Li  2 , Dana K Andersen  6 , William E Fisher  7 , Christopher E Forsmark  8 , Phil A Hart  9 , Stephen J Pandol  10 , Walter G Park  11 , Mark D Topazian  5 , Stephen K Van Den Eeden  12 , Jose Serrano  6 , Darwin L Conwell  13 , Dhiraj Yadav  3 ; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)
Affiliations
Observational Study

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis

Jami L Saloman et al. J Pain. 2023 Dec.

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.

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Figures

Figure 1.
Figure 1.. Subject selection.
The number of subjects were selected based on availability of serum and power analyses.
Figure 2.
Figure 2.. Final Study Cohort.
Subjects by pain group.
Figure 3.
Figure 3.. Serum biomarker expression by pain subtype.
A) TGFβ1 is significantly higher in the nociceptive CP group compared to the no pain CP group. B) Circulating GP130 is significantly higher than no pain or pain without a neuropathic component. The middle line of the boxplots represent mean, and the upper and lower lines of the boxes are 75% and 25% quantiles.
See this image and copyright information in PMC

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