An Analysis of Biomarkers in Patients with Chronic Pain

Background: Because of the subjective nature of current pain assessments, limited efficacy oftreatment options and risks associated with opioid abuse and diversion, the need for objectivedata to assist with chronic pain management has never been greater. Successful identificationof mechanistic biomarkers would not only improve our understanding and ability to accuratelydiagnose pain disorders but would also facilitate the development of disease-modifying pain drugs.Objectives: The objective of this study was to determine and evaluate the prevalence of abnormalbiomarker findings in a population of patients with chronic pain.Study Design: Retrospective, observational study.Setting: Data analysis of biomarker test results was performed at a single industry site (EthosResearch & Development, Newport, KY) from clinical samples collected and analyzed from July toDecember 2018.Methods: A novel, pain-specific biomarker test panel that evaluates biomarkers of systemicinflammation, oxidative stress, neurotransmitter turnover, and micronutrient status was employedto determine the prevalence of abnormal findings in 17,834 unique patient samples analyzedat a national reference laboratory (Ethos Laboratories, Newport, KY). Patient biomarker resultswere considered abnormal if they were outside of the 95% confidence interval reference rangesestablished using a healthy population of donors who had no history of chronic pain or opioid use.Results: A total of 77% of patients with chronic pain exhibited at least one abnormal biomarkerresult (n = 13,765). The most common abnormal biomarker finding was elevated quinolinic acid,which was observed in 29% of patients (n = 5,107). Elevated pyroglutamate, indicative of glutathionedepletion, was observed in 19% of patients (n = 3,314). Elevated xanthurenic acid, indicative of vitaminB6 insufficiency, was observed in 17% of patients (3,025). Elevated levels of the acrolein metabolite3-hydroxypropyl mercapturic acid were observed in 21% of patients (n = 3,667). Elevated methylmalonicacid, indicative of a vitamin B12 deficiency, was observed in 10% of patients (n = 1,827), whereasabnormally low levels of neurotransmitter metabolites were observed in 8% of patients (n = 1,456).Limitations: Medications and/or conditions other than those associated with chronic pain werenot evaluated as potential causes of abnormal biomarker findings.Conclusions: A novel biomarker assay that measures objective correlates to the neurobiologicalprocesses underlying chronic pain reveals a high prevalence of atypical biochemistry in a populationof patients with pain. Abnormal biomarker findings presented here provide objective supportfor the role of cytokine-mediated inflammation, oxidative stress, abnormally low production ofneurotransmitters, and micronutrient deficiencies in the development or worsening of chronicpain. This unique panel of functional pain biomarkers provides practitioners with novel, objectiveinsight into the underlying causes of pain, which will pave the way for truly personalized painmedicine. Correcting abnormal biomarker findings with targeted, nonopioid therapies to improvepatient function and alleviate pain potentially could lessen the opioid burden and drastically reducehealth care costs.Key words: Biomarker, pain, inflamation, oxidative stress, neurotransmitter, micronutrientdeficiency, Kynurenine Pathway