Patterns of Muscle Health in Single- and Multi-Site Chronic Pain: A UK Biobank Normative Modeling Study

Background: Chronic pain is associated with impaired muscle health, but whether these changes reflect site-specific factors, broader systemic factors, or both remains unclear. The purpose of this study is to determine whether normative markers of muscle health derived from MRI show site-specific patterns in chronic pain. Methods: UK Biobank participants who underwent whole-body MRI from 2006 to 2010 were included in this retrospective cross-sectional study. The MuscleMap Toolbox quantified volume and intramuscular fat (IMF) in 42 muscles of the abdomen, pelvis, and thigh. Normative models trained on a no pain group generated muscle-specific deviations from normal (i.e., Z-scores) for single- and multi-site chronic and acute pain. Results: Of 17,843 participants, the primary site-specific analysis included 9,704 no pain, 885 single-site chronic back pain (CBP), 438 single-site chronic hip pain (CHP), and 1,315 single-site chronic knee pain (CKP) participants (n=12,342; mean age 63.7{+/-}7.5 years; 52.7% female). Additional analyses included single-site chronic neck/shoulder pain, acute pain, and multi-site chronic pain groups. In CBP, deviations were localized to abdominal muscles, with decreased volume in 6/8 and increased IMF in 6/8. In CHP, deviations were broad, with decreased volume in 3/8 of the abdominal and 14/26 of the thigh muscles, and increased IMF in 6/8 of the abdominal, 5/8 of the pelvic, and 4/26 of the thigh muscles. In CKP, deviations were localized to thigh muscles, with decreased volume in 8/26 and increased IMF in 6/26. Acute pain groups showed no significant differences except for decreased volume in one thigh muscle in acute knee pain. With each additional chronic pain site, volume decreased ({beta}=-.078;IQR:-0.100-0.051), and IMF increased ({beta}=.085;IQR:0.066-0.101). Combined Z-scores classified chronic pain groups better than chance (accuracy: 48.6%;p<.001), but not acute pain groups (accuracy: 39.0%;p=.20). Conclusions: Whole-body MRI combined with AI-driven muscle segmentation and normative modeling revealed site-specific patterns of muscle health in single-site chronic pain.