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Rapid treatment-induced brain changes in pediatric CRPS

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Abstract

To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

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Acknowledgments

This study was primarily supported by National Institute of Neurological Disorders and Stroke Grants R01-NS-065051 and K24-NS-064050 (to D. Borsook), by National Institute of Child Health and Human Development K23 Career Development Award HD-067202 (to L. Simons), and by a Grant from the Mayday Foundation, New York. We would like to thank Charles Berde, MD Ph.D. for his support through the Sara Page Mayo Endowment for Pediatric Pain Research. We would like to thank Simona Sava, Ph.D. for contributing to the data collection.

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Authors and Affiliations

  1. P.A.I.N. Group, Boston Children’s Hospital, Center for Pain and the Brain, 9 Hope Avenue, Waltham, MA, 02453, USA

    Nathalie Erpelding, Laura Simons, Alyssa Lebel, Paul Serrano, Melissa Pielech, Lino Becerra & David Borsook

  2. Harvard Medical School, Boston, MA, USA

    Nathalie Erpelding, Laura Simons, Alyssa Lebel, Sanjay Prabhu, Lino Becerra & David Borsook

  3. Department of Radiology, Boston Children’s Hospital, Boston, MA, USA

    Sanjay Prabhu

  4. Massachusetts General Hospital, Boston, MA, USA

    Lino Becerra & David Borsook

  5. McLean Hospital, Belmont, MA, USA

    Lino Becerra & David Borsook

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  1. Nathalie Erpelding
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Correspondence to Nathalie Erpelding.

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Supplementary Figure 1: Patient Samples and Anlyses Strategies. Disease effects were investigated in 21 patients and 21 healthy controls. Treatment effects were studies in 20 patients and 20 healthy controls. Eighteen patients were used in both analyses; 3 patients with a pretreatment visit only were added to the sample to study disease effects, where 2 patients with both pretreatment and posttreatment visits but no healthy matched controls were added to the sample to investigate treatment effects. Accordingly, a total of 23 patients with CRPS participated in the study.

Supplementary Figure 2: Brain Gray Matter and Psychological Measures. A. The change in dlPFC GM correlated negatively with overall CDI (r = −0.53; p < 0.05) (left panel), CDI anhedonia (r = −0.50; p < 0.05) (middle panel), and CDI self-esteem (r = −0.60; p < 0.01) (right panel) at posttreatment. B. The Cau GM correlated positively with MASC subscale physical anxiety symptoms (r = 0.53; p < 0.05) at pretreatment. C. At pretreatment, the Cau GM correlated positively with overall PCS (r = 0.76; p < 0.01) (top left panel), PCS helplessness (r = 0.75; p < 0.05) (top middle panel), and PCS magnification (r = 0.83; p < 0.01) (top right panel). At posttreatment, the Cau GM correlated positively with overall PCS (r = 0.64; p < 0.05) (bottom left panel) and PCS helplessness (r = 0.64; p < 0.05) (bottom right panel). D. At pretreatment, the Hippo GM correlated positively with overall PCS (r = 0.81; p < 0.01) (top left panel), PCS helplessness (r = 0.74; p < 0.05) (top middle left panel), PCS magnification (r = 0.83; p < 0.01) (top middle right panel), and PCS rumination (r = 0.73; p < 0.05) (top right panel). At posttreatment, the Hippo GM correlated positively with overall PCS (r = 0.71; p < 0.05) (bottom left panel), PCS helplessness (r = 0.68; p < 0.05) (bottom middle left panel), PCS magnification (r = 0.70; p < 0.05) (bottom middle right panel), and PCS rumination (r = 0.71; p < 0.05) (bottom right panel).

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Erpelding, N., Simons, L., Lebel, A. et al. Rapid treatment-induced brain changes in pediatric CRPS. Brain Struct Funct 221, 1095–1111 (2016). https://doi.org/10.1007/s00429-014-0957-8

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