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5 Articles in this Series
Exercise Improves Chronic Pain Biomarkers
New Lidocaine Patch for Postherpetic Neuralgia
OPERA Study: Patients Satisfied With Topical Analgesics
Pharmacist-Led Chronic Pain Service
Reaching Clinical Targets for PTSD Patients With Fibromyalgia

Exercise Improves Chronic Pain Biomarkers

An interview with Jennifer Kawi, PhD

Finding reliable objective measures for chronic pain is an important step to advancing pain management. Recently, investigators have identified a variety of pain biomarkers, understood as integral to nociceptive functioning, and have used them as therapeutic targets when assessing exercise as an intervention for chronic pain conditions. However, could such biomarkers function as actual objective measures for chronic pain, as well?

A team of researchers at the University of Nevada, led by Jennifer Kawi, PhD, had this question in mind when they conducted an extensive, systematic review of published clinical trials. They wanted to examine how exercise influenced the change in these biomarkers, and how such changes related to pain-related outcomes of chronic musculoskeletal nonmalignant pain conditions.1

Nearly 700 studies were reviewed, but only a dozen met the study’s inclusion criteria. Using the Jadad Scale, the researchers systematically assessed the studies’ methodological quality, finding that they were typically case-control studies examining how exercise interventions affected certain pain conditions, including chronic low back pain, ankylosing spondylitis, knee osteoarthritis, fibromyalgia, and chronic fatigue syndrome. Types of exercise interventions were diverse, including stretching, strength training, squats, aerobics, cycling, pool exercises, and spa-exercise therapy. Study durations varied, as well, from a few weeks to 18 months.

The researchers found that exercise had a noticeable hypoalgesic effect on certain pain conditions, particularly knee osteoarthritis and fibromyalgia, decreasing several inflammatory markers implicated in chronic pain pathways, including interleukin (IL)-6, IL-1b, IL-6, IL-8, IL-18, interferon gamma, C-reactive protein, and tumor necrosis factors [TNF]-alpha. Anti-inflammatory markers, like IL-10 and transforming growth factor (TGF-b1), significantly increased for ankylosing spondylosis and low back pain, respectively. The researchers also discovered that the neurotransmitter catechol-O-methyltransferase (COMT) was associated with pain, disability, fatigue, anxiety, and depression, following the exercise interventions. However, the review noted that there was a limitation in the inconsistent laboratory quality control measures used. The varying methodologies could have affected the findings.

“The potential translational value of biomarkers in chronic pain is evident although it remains a question whether biomarkers can be utilized as objective measures for risk assessment, diagnosis, and evaluation of chronic disease progression,” noted Dr. Kawi. Because of this, there is a need for replications of such longitudinal studies, using more uniformed methodological approaches and more substantial sample sizes.

Current studies are beginning to take these bigger strides, noted Dr. Kawi. By both using functional MRIs and blood samples, they are combining neurological and serological data in a search for possible correlations arising during an elicited pain response. “The question, however, is is ‘Does this really represent a true picture of a patient in chronic pain?’” Given the elicited pain is experimental, such a setting could just be an unreliable proxy to the real chronic pain ailments that Americans suffer.

Dr. Kawi also wants to investigate the role epigenetics play in the pathologies of chronic pain, including how environmental factors influence an individual’s predisposition to chronicity. “Those kinds of studies are really interesting, so that hopefully we can target more of our interventions to specific individuals that would respond better,” she said.


1. Kawi J, Lukkahatai N, Inouye J, Thomason D, Connelly K. Effects of exercise on select biomarkers and associated outcomes in chronic pain conditions: systemic review. Postgrad Med. 2015;Early Online:58.

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