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

Abstract

Introduction 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.

Therapeutic Potential of Downregulated Interleukin-6 Signaling for the Treatment of Chronic Pain: A Mendelian Randomization Study

“…41 A study with 689 participants found no association between IL-6 plasma concentration and chronic hip, shoulder, and neck pain. 35 The results of our research suggested that targeting the IL-6 pathway could potentially reduce the risk of developing chronic back and knee pain. It is important to exercise caution when interpreting these findings, as the effects of targeting the IL-6 pathway specifically on chronic pain intensity and duration are still unknown.…”

“…Although not as well-established as the correlation found between variation at IL6R and specific health outcomes, previous studies have reported phenotypic implications associated with variations in gp130. 25,26 We aimed to develop genetic instruments using a recent Genome-Wide Association Study (GWAS) involving 35,287 participants from the DECODE consortium. 27 We extracted 24 independent SNPs (with a P-value lower than 5*10 −8 and an r2 below 0.1) and linked to gp130 levels within a range of 300 kb of the gp130 area (Table S6).…”

“…34 A cross-sectional study found that IL-6 was positive correlated with chronic knee pain, although it could not rule out the risk of reverse causation. 35 A recent meta-analysis found patients with chronic low back pain had elevated IL-6 level. 36 Animal experimentation indicated that injecting IL6/sIL6R into rat knee joints increased spinal neuron responsiveness to mechanical stimulation.…”

Causal relationships between systemic inflammatory cytokines and adhesive capsulitis: a bidirectional Mendelian randomization study

“…Notably, Norman et al. investigated the relationship between inflammation biomarkers and musculoskeletal pain, revealing no significant association between RANTES and shoulder pain ( 33 ). Despite this, direct studies on the relationship between RANTES and AC are limited, warranting further investigation.…”