The influence of pain-related fear levels on structural brain changes in pediatric complex regional pain syndrome

Abstract

Complex Regional Pain Syndrome (CRPS) is a chronic neuropathic pain condition associated with significant alterations in the somatosensory and motor cortex brain regions. Cognitive-affective alterations have recently been recognized in patients suffering with CRPS, however, relatively little neuroimaging research has been done to examine these dimensions. Moreover, many children and adolescents suffer from CRPS, but very little is known about the impact of this condition on brain states in the pediatric population. The aim of this paper is to assess the structural brain differences between children with CRPS and healthy controls and to examine to what degree fear level influences such differences. This study is part of a larger investigation that integrates functional and structural brain differences to evaluate fear-related brain circuitry in patients with CRPS. Thirty-seven patients with CRPS were age and gender matched with 35 healthy controls. The two groups underwent structural magnetic resonance imaging (MRI) scans as well as completed the Fear of Pain Questionnaire, child report (FOPQ). To examine gray matter differences, voxel-based morphometry (VBM) and cortical thickness (CT) analysis was completed. Patients with CRPS in this study had an average age of 13.2 (SD=2.7) and were predominantly female (73%). Of the 35 patients who completed FOPQ, 49% reported clinically significant pain-related fear. Compared with healthy controls, CRPS patients had significantly less in gray matter (GM) volume in pain- and fear-related brain regions, including the dorsolateral prefrontal gyrus, motor and somatosensory cortex, anterior and posterior cingulate cortex, nucleus accumbens, putamen, amygdala, and hippocampus. Furthermore, gray matter decreases in regions such as anterior midcingulate cortex, nucleus accumbens, and putamen were associated with elevated pain-related fear in patients. Differences in gray matter volume in fear-circuitry areas could potentially be one mechanism by which abnormal fear learning and extinction develops in youth suffering with CRPS. Further research examining brain changes post-treatment is needed to determine if treatments that target improving pain and fear levels are associated with concomitant normalization of brain structures.