Katherine S Norman,1,2 Adam P Goode,1â 3 Carolina Alvarez,4,5 David Hu,4,5 Steven Z George,2,3 Todd A Schwartz,4,6 Stephanie T Danyluk,2 Rebecca Fillipo,7 Virginia B Kraus,2,8,9 Janet L Huebner,8 Rebecca J Cleveland,4,5 Joanne M Jordan,4,5,10,11 Amanda E Nelson,4,5 Yvonne M Golightly4,11,12 1Department of Population Health Sciences, Duke University, Durham, NC, USA; 2Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA; 3Duke Clinical Research Institute, Duke University, Durham, NC, USA; 4Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA; 5Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; 6Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; 7Duke Department of Physical Therapy and Occupational Therapy, Duke University Health System, Durham, NC, USA; 8Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; 9Duke Department of Medicine, Duke University School of Medicine, Durham, NC, USA; 10Department of Orthopedics, University of North Carolina, Chapel Hill, NC, USA; 11Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; 12College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, USACorrespondence: Adam P Goode, Department of Orthopedic Surgery, Duke Clinical Research Institute, Duke University, Durham, NC, USA, Tel +1 919-681-6157, Fax +1 919-684-1846, Email Adam.Goode@duke.eduIntroduction: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: epidemiology, pain, musculoskeletal, population health