An Analysis of Biomarkers in Patients with
Chronic Pain
Authors: Gunn Joshua 
Published: March 2021

Background: Because of the subjective nature of current pain assessments, limited efficacy of
treatment options and risks associated with opioid abuse and diversion, the need for objective
data to assist with chronic pain management has never been greater. Successful identification
of mechanistic biomarkers would not only improve our understanding and ability to accurately
diagnose 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 abnormal
biomarker 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 (Ethos
Research & Development, Newport, KY) from clinical samples collected and analyzed from July to
December 2018.
Methods: A novel, pain-specific biomarker test panel that evaluates biomarkers of systemic
inflammation, oxidative stress, neurotransmitter turnover, and micronutrient status was employed
to determine the prevalence of abnormal findings in 17,834 unique patient samples analyzed
at a national reference laboratory (Ethos Laboratories, Newport, KY). Patient biomarker results
were considered abnormal if they were outside of the 95% confidence interval reference ranges
established 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 biomarker
result (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 glutathione
depletion, was observed in 19% of patients (n = 3,314). Elevated xanthurenic acid, indicative of vitamin
B6 insufficiency, was observed in 17% of patients (3,025). Elevated levels of the acrolein metabolite
3-hydroxypropyl mercapturic acid were observed in 21% of patients (n = 3,667). Elevated methylmalonic
acid, indicative of a vitamin B12 deficiency, was observed in 10% of patients (n = 1,827), whereas
abnormally 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 were
not evaluated as potential causes of abnormal biomarker findings.
Conclusions: A novel biomarker assay that measures objective correlates to the neurobiological
processes underlying chronic pain reveals a high prevalence of atypical biochemistry in a population
of patients with pain. Abnormal biomarker findings presented here provide objective support
for the role of cytokine-mediated inflammation, oxidative stress, abnormally low production of
neurotransmitters, and micronutrient deficiencies in the development or worsening of chronic
pain. This unique panel of functional pain biomarkers provides practitioners with novel, objective
insight into the underlying causes of pain, which will pave the way for truly personalized pain
medicine. Correcting abnormal biomarker findings with targeted, nonopioid therapies to improve
patient function and alleviate pain potentially could lessen the opioid burden and drastically reduce
health care costs.
Key words: Biomarker, pain, inflamation, oxidative stress, neurotransmitter, micronutrient
deficiency, Kynurenine Pathway