107: Widespread gray matter volume reduction in pediatric MSK pain associates with pain catastrophizing

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Neuroanatomical circuit analysis, , ,

Background and Aims: Pediatric chronic MSK pain adversely affects quality of life(1). Pain catastrophizing is associated with pain morbidity, emotional distress, and treatment outcomes in this population(2). Therefore, some pain management strategies target pain catastrophizing(3). However, the structural neural underpinnings of pain catastrophizing remain poorly understood, and identifying these could provide therapeutic neural targets(4,5). Here, we identify the neural correlates of pain catastrophizing in adolescents with chronic MSK pain, compared to pain-free controls to assess specificity. We hypothesized that lower gray matter volume in regions associated with pain catastrophizing would correlate with higher catastrophizing scores in patients but not controls.

Methods: Sixty-nine participants (33 MSK pain patients, 36 controls; age- and sex-matched) consented to REB-approved procedures. As part of a larger study, participants underwent T1-weighted MRI scanning. Data were preprocessed for voxel-based morphometry with DeepMRI. A behaviour partial least squares (bPLS) analysis was used to examine group differences in gray matter associations with Pain Catastrophizing Scale, child(2) (PCS-C) scores. Statistical significance was assessed using permutation testing, and voxelwise reliability was evaluated using bootstrap resampling. Bootstrap ratios (BSRs) were thresholded at |BSR| > 3.1 or a 99.9% confidence interval to identify the pattern of regions that reliably contributed to significant latent variables.

Results: Child pain catastrophizing scores were significantly different (p = 4.65 x 10-11) between patients and controls. Behavioral PLS identified a significant latent variable (LV1; p = 0.02), revealing a distributed pattern of decreased gray matter volumes associated with higher PCS-C scores in patients, with no stable contribution from controls. Dominant negative saliences included the posterior cingulate, the mid-cingulate, orbitofrontal, somatosensory, posterior parietal, dorsolateral prefrontal cortices, as well as bilateral amygdala.

Conclusions: We found that in adolescents with chronic MSK pain, greater pain catastrophizing was associated with lower gray matter volume in limbic regions (e.g., amygdala, mid-cingulate), as well as somatomotor and cognitive areas. This relationship was not observed in pain-free controls, supporting the specificity of these findings. Future studies should examine the functional changes associated with these structural alterations, which could then be targeted by neuromodulation approaches. Additionally, parsing the contributions of these regions to different aspects of pain morbidity could help translate these neuroimaging findings into clinical interventions.

References: [1].Zernikow B, Wager J, Hechler T, Hasan C, Rohr U, Dobe M, Meyer A, Hübner-Möhler B, Wamsler C, Blankenburg M. Characteristics of highly impaired children with severe chronic pain: a 5-year retrospective study on 2249 pediatric pain patients. BMC Pediatr 2012;12:54.

[2]. Crombez G, Bijttebier P, Eccleston C, Mascagni T, Mertens G, Goubert L, Verstraeten K. The child version of the pain catastrophizing scale (PCS-C): a preliminary validation. PAIN®. 2003;104:639-646.

[3] Yamin, JB, Meints, SM, & Edwards, RR. Beyond pain catastrophizing: rationale and recommendations for targeting trauma in the assessment and treatment of chronic pain. Expert Rev. Neurother, 2024;3: 231-234.

[4]Galambos A, Szabó E, Nagy Z, Édes AE, Kocsel N, Juhász G, Kökönyei G. A systematic review of structural and functional MRI studies on pain catastrophizing. J Pain Res. 2019 Apr 11;12:1155-1178.

[5]Miller MM, Meints SM, Hirsh AT. Catastrophizing, pain, and functional outcomes for children with chronic pain: a meta-analytic review. Pain. 2018 Dec;159(12):2442-2460.

Presenting Author: Spencer S. Abssy
Submitting Author: Spencer Abssy

Senior Author: Massieh Moayedi

IASP 2026 Global Year theme of Neuropathic Pain: No

• Spencer S. Abssy: HBSc - Centre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, Canada
• Andrea B. Protzner: PhD - Department of Psychology, University of Calgary, Calgary, Canada
• Jennifer Stinson: PhD - Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada
• Jewel N. White: PhD - Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Saül Pascual-Diaz: PhD - Serra Hunter Programme, Department of Medicine, University of Barcelona, Barcelona, Spain
• Marie-Eve Hoeppli: PhD - Department of Experimental Psychology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University, Düsseldorf, Germany
• Emma Biggs: PhD - Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Martin S Angst: PhD - Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Nima Aghaeepour: PhD - Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Brice Gaudillière: PhD - Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Marina López-Solà: PhD - Serra Hunter Programme, Department of Medicine, University of Barcelona, Barcelona, Spain
• Robert C. Coghill: PhD - Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
• Christopher King: PhD - Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
• Laura E. Simons: PhD - Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
• Massieh Moayedi: PhD - Centre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, Canada