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Biomarkers Offer Insight into Chronic Pain Assessment

October 11, 2021
New research suggests that severe biochemical abnormalities may play a role in the etiology of chronic pain.

Assessing patients’ pain is one of the most difficult challenges for physicians who treat conditions that involve chronic pain. Many psychosocial factors combine to influence the nature and degree of pain. Despite all the numerical scales and cartoon faces, clinicians still don’t have a good way of measuring pain.

A recent study cross-validated a common patient-reported outcome measure testing biomarkers associated with pain (Image: iStock).

“Pain is,” says Padma Gulur, MD, professor of anesthesiology and population health at Duke University School of Medicine, “what the patient says it is.” She adds that functional MRI has helped us understand what parts of the brain light up when patients are in pain, but that is only a mechanistic understanding and of no use as an assessment tool.

The need for a better assessment tool motivated a recent study cross-validating a common patient-reported outcome measure (PRO) and a test of biomarkers associated with pain.

Chronic Pain Linked to Individual Biomarkers

The Foundation Pain Index (FPI) is a laboratory test that identifies 11 endogenous biomarkers, all known to play a role in chronic pain. The PROMIS-29 profile is a measurement tool for assessing the intensity of pain using several domains, such as physical function, pain interference, fatigue, and depression. A study published this August by Pope et al set out to map associations between abnormal biochemical functions and PROMIS-29 domains in people experiencing chronic pain.1

For this retrospective, observational study, the researchers gathered FPI results and PROMIS-29 scores for patients with chronic pain, all from a single clinic in Santa Rosa, California. Individuals who were being prescribed medications that could interfere with the biomarkers of the FPI assay were excluded, as were patients with a history of hepatic or renal disease. Pain was defined according to the updated definition offered by the International Association for the Study of Pain (IASP): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” Pain was classified as chronic if it had lasted for longer than 3 months.

Urine samples were collected from patients within 15 days of their initial clinic visits after completing the PROMIS-19 survey. Biomarker analysis of the samples and determination of FPI were completed.

Associations Between Pain Biomarkers and Promis-29 Domains

The final cohort included 298 patients, with a mean age of 60.7 years; 55% were female. The researchers described this cohort as representing “a population of individuals with severe chronic pain and pain interference that impacts activities of daily living and represents the broader chronic pain population in terms of their multidimensional psychometric profile.”1 In the final analysis, 87% of patients had at least one abnormal biomarker, the most common being elevated quinolinic acid, a neurotoxic NMDA agonist. Among the subjects with chronic pain, the mean FPI score was 35.9 on a scale of 0 to 100.

A correlation analysis of PROMIS-29 domains and biomarker data found that the PROMIS-29 physical-function domain was strongly associated with four of the FPI component biomarkers (5-hydroxyindoleacetic acid, quinolinic acid, kynurenic acid, and hydroxymethylglutarate) and showed close to significant associations with xanthurenic acid (biomarker of vitamin B-6 status) and vanilmandelate (metabolite of epinephrine/norepinephrine). Pain interference and pain impact were also associated with several component biomarkers.

In all, the results demonstrated a strong association between FPI scores and validated clinical assessments in patients with chronic pain.

Biomarkers, Pain, and Practical Takeaways

The fact that higher FPI scores were associated with worse PROMIS-19 scores across most of the domains (physical function, pain impact scores, fatigue, pain interference, and depression)suggests that more severe biochemical abnormalities may play a role in the etiology of chronic pain. “Objective identification of underlying biochemical pain determinants or contributing factors will provide practitioners with novel treatment options aimed at correcting underlying biochemical function,” the authors wrote in their paper.1

The researchers expect that this cross-validation of FPI and PROMIS-29 domains will encourage more clinicians to adopt PROMIS-29 when assessing patients presenting with chronic pain.

Dr. Gulur agrees that there is great promise here. However, she cautions that this is an evolving field. “At this stage, we don’t know what biomarkers to look for.” Like the fMRI studies, the biomarkers provide a mechanistic understanding but are not an assessment tool. “There is much value in these studies,” she says, “information that could result in more research,” but she points out, there is still a long way to go before this will be useful to clinicians. “Is this ready for prime time in terms of clinical use? Not yet.”


Disclosure: In the original paper, three of the researchers cited a variety of conflicts of interest, including relationships with Ethos Labs which conducted the sample analysis.

Last updated on: October 12, 2021
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