Preprint Patterns of Muscle Health in Single- and Multi-Site Chronic Pain: A UK Biobank Normative Modeling Study, 2026, Kaptan et al.

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Patterns of Muscle Health in Single- and Multi-Site Chronic Pain: A UK Biobank Normative Modeling Study
Merve Kaptan; Yiyu Wang; Augustijn A A de Boer; Ananya Goyal; Skylar Holmes; Kerem Ozkan; Sandrine Bedard; Teresa Indriolo; Christine S W Law; Dario Pfyffer; Joel Fundaun; Estifanos Berhe; Garry E Gold; Akshay Chaudhari; Anoosha Pai S; Anthony A Gatti; Feliks Kogan; Brian A Hargreaves; Scott L Delp; John Ratliff; Serena Hu; Anand Veeravagu; Atman Desai; Suzanne Tharin; Todd Alamin; Andrew C Smith; Marnee J McKay; Brian Kim; Robert Walsh; Alec Schielke; Dean Dennis; Johannes Decker; Benjamin De Leener; Julien Cohen-Adad; Zachary A Smith; Fauziyya Muhammad; James M Elliott; Andre F Marquand; Sean Mackey; Evert Onno Wesselink; Kenneth A Weber

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 (β=−.078;IQR:−0.100−0.051), and IMF increased (β=.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.

Web | DOI | PDF | Preprint: MedRxiv | Open Access
 
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