Complex Regional Pain Syndrome Is Associated With Structural Abnormalities in Pain-Related Regions of the Human Brain

Abstract

Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities, and frequently motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging (sMRI) to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls . Analyses were carried out using a whole brain voxel-based morphometry (VBM) approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems.

Complex regional pain syndrome

“…Box 2 | Possible mechanisms involved in complex regional pain syndrome Nerve injury [31][32][33][34] Ischemic reperfusion injury or oxidative stress [35][36][37][38][39][40] Central sensitization [41][42][43] Peripheral sensitization 44 45 Altered sympathetic nervous system function or sympathoafferent coupling [46][47][48][49][50][51][52] Inflammatory and immune related factors Brain changes [78][79][80][81][82][83][84][85][86][87][88][89] Genetic factors [90][91][92] Psychological factors and disuse [93][94][95][96][97][98][99][100][101][102][103] deep tissues after injury have also been suggested as triggers for the onset of CRPS. …”

“…123 Thirty patients with post-traumatic CRPS were followed without treatment for an average of 13 months after diagnosis; three patients were withdrawn from the study to be given treatment, and CRPS resolved over the have also been noted-patients with CRPS showed reduced gray matter volume compared with healthy controls in brain regions underlying the affective component of pain (insula and cingulate cortex). 87 Evidence suggests that the altered somatosensory representation in patients with CRPS can normalize with successful treatment. 88 89 In light of the similar normalization of specific brain changes (such as reduced gray matter volume) seen with successful treatment of other forms of chronic pain, 115 116 at least some of the brain changes in CRPS are likely to be an effect rather than a cause.…”

A Critical Review of Neurobiological Factors Involved in the Interactions Between Chronic Pain, Depression, and Sleep Disruption

“…In these individuals, atrophy of the medial prefrontal cortex (mPFC), the hippocampus, and the anterior cingulated cortex (ACC) has been reported. [24][25][26] A substantial body of research has addressed changes in the brain that occur in depression. Analyses of both structural changes, and of functional changes in patterns of brain activation, exist in the literature.…”

Complex regional pain syndrome: The matter of white matter?

“…More recently, morphometric changes have been found in the CRPS patients' brains with anatomical T1 MRI (Baliki, Schnitzer, Bauer, & Apkarian, 2011; Barad, Ueno, Younger, Chatterjee, & Mackey, 2014; Geha et al., 2008; Pleger et al., 2014), and we have observed the enlargement of choroid plexus (Zhou, Hotta, Lehtinen, Forss, & Hari, 2015), in line with the suggestion that neuroinflammation might play a role in the pathophysiology of CRPS (Linnman, Becerra, & Borsook, 2013). In neuroinflammatory diseases, brain's white matter can possess microstructural abnormalities although it appears normal in anatomical T1 MRI (Filippi et al., 2012).…”