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

Kaptan, M.; Wang, Y.; de Boer, A. A. A.; Goyal, A.; Holmes, S.; Ozkan, K.; Bedard, S.; Indriolo, T.; Law, C. S. W.; Pfyffer, D.; Fundaun, J.; Berhe, E.; Gold, G. E.; Chaudhari, A.; Pai S, A.; Gatti, A. A.; Kogan, F.; Hargreaves, B. A.; Delp, S. L.; Ratliff, J.; Hu, S.; Veeravagu, A.; Desai, A.; Tharin, S.; Alamin, T.; Smith, A. C.; McKay, M. J.; Kim, B.; Walsh, R.; Schielke, A.; Dennis, D.; Decker, J.; De Leener, B.; Cohen-Adad, J.; Smith, Z. A.; Muhammad, F.; Elliott, J. M.; Marquand, A. F.; Mackey, S.; Wesselink, E. O.; Weber, K. A.

2026-06-22 radiology and imaging
10.64898/2026.06.19.26356062 medRxiv
Show abstract

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.

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