Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project.



Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain.


This cross-sectional analysis included 689 community-based participants. Self-reported symptoms (ie, pain, aching, or stiffness) were ascertained about the neck, upper back/thoracic, low back, shoulders, elbows, wrist, hands, hips, knees, ankles, and feet. Measured analytes included CXCL-6, RANTES, HA, IL-6, BDNF, OPG and NPY. A standard dolorimeter measured PPT. Logistic regression was used determine the association between biomarkers and PPT with individual and summed sites of pain.


Increased IL-6 and HA were associated with knee pain (OR=1.30, 95% CI 1.03, 1.64) and (OR=1.32, 95% CI 1.01, 1.73) respectively; HA was also associated with elbow/wrist/hand pain (OR=1.60, 95% CI 1.22, 2.09). Those with increased NPY levels were less likely to have shoulder pain (OR=0.56, 95% CI 0.33, 0.93). Biomarkers HA (OR=1.50, 95% CI 1.07, 2.10), OPG (OR=1.74, 95% CI 1.00, 3.03), CXCL-6 (OR=1.75, 95% CI 1.02, 3.01) and decreased PPT (OR=3.97, 95% CI 2.22, 7.12) were associated with multiple compared to no sites of pain. Biomarker HA (OR=1.57, 95% CI 1.06, 2.32) and decreased PPT (OR=3.53, 95% CI 1.81, 6.88) were associated with multiple compared to a single site of pain.


Biomarkers of inflammation (HA, OPG, IL-6 and CXCL-6), pain (NPY) and PPT may help to understand the etiology of single and multiple pain sites.





Published Version (Please cite this version)


Publication Info

Norman, Katherine S, Adam P Goode, Carolina Alvarez, David Hu, Steven Z George, Todd A Schwartz, Stephanie T Danyluk, Rebecca Fillipo, et al. (2022). Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project. Journal of pain research, 15. pp. 2393–2404. 10.2147/jpr.s365187 Retrieved from

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Adam Payne Goode

Professor in Orthopaedic Surgery

Dr. Goode is an Associate Professor in the Department of Orthopedic Surgery. He is a physical therapist by clinical training and epidemiologist by scientific training. His focus is on understanding the etiology of low back pain and other chronic musculoskeletal conditions and improving the delivery of care for patients with acute and chronic musculoskeletal conditions.  In his research he has published in the areas of the relationship between individual radiographic features in the lumbar spine and clinical symptoms, biomarkers and peripheral joint osteoarthritis. 


Steven Zachary George

Laszlo Ormandy Distinguished Professor of Orthopaedic Surgery

Dr. George’s primary interest is research involving biopsychosocial models for the prevention and treatment of chronic musculoskeletal pain disorders.  His long term goals are to 1) improve accuracy for predicting who is going to develop chronic pain; and 2) identify non-pharmacological treatment options that limit the development of chronic pain conditions.  Dr. George is an active member of the American Physical Therapy Association, United States Association of the Study of Pain, and International Association for the Study of Pain. 

Dr. George’s research projects have been supported by the National Institutes of Health, Department of Defense, and Orthopaedic Academy of the American Physical Therapy Association.  Dr. George and his collaborators have authored over 300 peer-reviewed publications in leading medical, orthopaedic surgery, physical therapy, rehabilitation, and pain research journals.  He currently serves as Deputy Editor for Physical Therapy and is an Editorial Board Member for the Journal of Pain. Dr. George has also been involved with clinical practice guideline development for the Academy of Orthopaedic Physical Therapy and the American Psychological Association. 

Dr. George has been recognized with prestigious research awards from the American Physical Therapy Association, American Pain Society, and International Association for the Study of Pain. For example from the American Physical Therapy Association: he was named the  21st John H.P. Maley Lecturer, recognized as a Catherine Worthingham Fellow in 2017, and selected for the Marian Williams Award for Research in Physical Therapy in 2022.    


Virginia Byers Kraus

Mary Bernheim Distinguished Professor of Medicine

Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.

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