Clinical Validation of a Multi-Biomarker Assay for the Evaluation of Chronic Pain Patients in a Cross-Sectional, Observational Study

Kasra Amirdelfan, Jason E Pope, Joshua Gunn, Melissa M Hill, Bradley M Cotten, John E Beresh, Douglas Dobecki, Nathan Miller, Pankaj Mehta, George Girardi, Timothy R Deer, Kasra Amirdelfan, Jason E Pope, Joshua Gunn, Melissa M Hill, Bradley M Cotten, John E Beresh, Douglas Dobecki, Nathan Miller, Pankaj Mehta, George Girardi, Timothy R Deer

Abstract

Introduction: Chronic pain assessment and post-treatment evaluation continues to be challenging due to a lack of validated, objective tools to measure patient outcomes. Validation of mechanistic pain biomarkers would allow clinicians to objectively identify abnormal biochemistry contributing to painful symptoms.

Methods: We describe the clinical validation of a multi-biomarker assay with algorithmic analysis known as the Foundation Pain Index (FPI) in diverse cohorts of chronic pain patients in a prospective, cross-sectional, observational validation study. Levels of 11 urinary pain biomarkers were measured and tabulated using a proprietary algorithm to generate FPI scores for chronic pain subjects (N = 153) and age- and sex-matched pain-free controls (N = 334).

Results: FPI scores were significantly correlated with the 36-Item Short Form Health Survey (SF-36) scores among chronic pain subjects (P value < 0.015) and specific components of SF-36, including emotional well-being, limitations due to emotional problems, and general health (P value < 0.05). Area under ROC analysis (AUROC) revealed FPI to accurately distinguish biomarker profiles between pain-free and chronic pain cohorts (AUROC: 0.7490, P value < 0.0001) as well as the SF-36 scores between chronic pain subjects with low vs. high FPI scores (AUROC: 0.7715, P value < 0.01).

Conclusions: Our findings establish the validity and discriminatory power of a novel multi-biomarker test that evaluates the role of biochemistry in chronic pain and correlates with clinical assessments of patients. This test provides novel, reproducible, objective data which may pave the way for non-opioid therapeutic strategies to treat chronic pain.

Keywords: Biomarker; Inflammation; Kynurenine; Micronutrient; Pain.

Figures

Fig. 1
Fig. 1
ROC curve of FPI. Healthy (n = 334) and pain (n = 153) subjects were matched for sex (female: 50%) and age (avg per group: 55 years old). AUROC area under the receiver operating characteristic
Fig. 2
Fig. 2
Comparison of means (non-parametric t test) of FPI. Healthy (n = 334) and pain (n = 153) subjects were matched for sex (female: 50%) and age (avg per group: 55 years old). ***P value < 0.0001
Fig. 3
Fig. 3
Comparison of means (non-parametric t test) of FPI severity and SF-36 scores. Clinical evaluations were compared between randomly selected pain patients with moderately high and high FPI severity scores (> 75 FPI; n = 20) and low FPI severity scores (< 20 FPI; n = 20). **P value < 0.001
Fig. 4
Fig. 4
ROC curve of FPI severity and SF-36 scores. ROC analysis was performed between randomly selected pain patients with moderately high and high FPI severity scores (> 75 FPI; n = 20) and low FPI severity scores (< 20 FPI; n = 20). AUROC area under the receiver operating characteristic curve
Fig. 5
Fig. 5
Association between SF-36 scores and FPI severity among chronic pain patients. Data is represented as mean ± SEM and was analyzed by linear trend analysis of one-way ANOVA. MOD moderate, M.HIGH moderately high

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