Background & Aims
Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). Multiple underlying mechanisms contribute to CP pain making successful treatment difficult.(1) The identification of biomarkers for subtypes of pain, such as neuropathic and nociceptive components, could provide viable targets for non-opioid interventions and the development of mechanistic approaches to pain management in CP. In a cross-sectional analysis, serum levels of 19 putative biomarkers for nociceptive and neuropathic pain were assessed; TGFbeta1 was significantly higher in the Nociceptive Pain versus the No Pain group.(2) GP130, a co-receptor for IL-6, was significantly higher in the Mixed (neuropathic+nociceptive) pain group compared to those lacking a neuropathic pain component. Pain in chronic disease can be dynamic so the objective of the current study was to compare the PROMIS-PQ classification at 1 yr follow-up and to validate the putative biomarkers.
Methods
Neuropathic and nociceptive pain classification was based on a cut-off of T-score greater than or equal to 50 on the Neuropathic and Nociceptive PROMIS-PQ questionnaires. Cytokines and growth factors were measured using the Meso Scale Discovery multiplex platform, an electrochemiluminescent immunoassay. Continuous T-scores and PROMIS-PQ category were compared to protein levels using correlation analyses.
Results
At enrollment, 17.6% (120/681) subjects with CP reported no pain in the previous year. Of those, 29% reported experiencing pain during the 1 yr follow-up whereas 18% of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data. Approximately half (53.3%) of those individuals changed PROMIS-PQ classification between baseline and follow-up. We assessed baseline and 1 yr follow-up serum samples from 128 subjects. At 1 yr, serum TGF?1 levels were negatively correlated with nociceptive T-scores (p=0.006). GP130 was significantly correlated with both nociceptive (p=0.012) and neuropathic T-scores (p=0.043) at 1 yr, which is consistent with findings at baseline that GP130 was significantly elevated in individuals with Neuropathic and/or Mixed (both neuropathic and nociceptive) pain.(2)
Conclusions
While preclinical studies have shown that targeting TGFbeta1 is sufficient to inhibit sensory neuron hyperexcitability and pain, the association between TGFbeta1 and pain is not maintained overtime, suggesting it is a poor pain biomarker. However, GP130 appears to be a potential biomarker for ongoing pain over time. That GP130 association with pain subtype changes may reflect a lack of sensitivity of the PROMIS-PQ instrument.
References
1.Saloman JL, Conwell DL, Fogel E, Vege SS, Li L, Li S, Andersen DK, Fisher WE, Forsmark CE, Hart PA, Pandol SJ, Park WG, Phillips AE, Topazian M, Van Den Eeden SK, Serrano J, Yadav D, Consortium for the Study of Chronic Pancreatitis D, Pancreatic C. Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies. Pain. 2022
2.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, Consortium for the Study of Chronic Pancreatitis D, Pancreatic C. Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis. J Pain. 2023
3.Yadav D, Park WG, Fogel EL, Li L, Chari ST, Feng Z, Fisher WE, Forsmark CE, Jeon CY, Habtezion A, Hart PA, Hughes SJ, Othman MO, Rinuado JA, Pandol SJ, Tirkes T, Serrano J, Srivastava S, Van Den Eeden SK, Whitcomb DC, Topazian M, Conwell DL, on behalf of the Consortium for the Study of Chronic Pancreatitis D, and Pancreatic Cancer. PROspective Evaluation of Chroinc Pancreatitis for EpidEmiologic and Translational StuDies. Pancreas. 47:1229-1238, 2018
Presenting Author
Jami L. Saloman
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Abdominal and Pelvic Pain