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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 by 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 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 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.This paper presents structural changes in the brains of patients with CRPS, helping us differentiate CRPS from other chronic pain syndromes and furthering our understanding of this challenging disease.

SUBMITTER: Barad MJ

PROVIDER: S-EPMC4784981 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain.

Barad Meredith J MJ Ueno Takefumi T Younger Jarred J Chatterjee Neil N Mackey Sean S

The journal of pain 20131107 2

<h4>Unlabelled</h4>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 by 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 to characterize differences in gray matter volume be ...[more]

PMID: 24212070

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Project description:Complex Regional Pain Syndrome (CRPS) is a multifactorial and disabling disorder with complex etiology and pathogenesis. Goals of therapy in CRPS should be pain relief, functional restoration, and psychological stabilization, but early interventions are needed in order to achieve these objectives. Several drugs have been used to reduce pain and to improve functional status in CRPS, despite the lack of scientific evidence supporting their use in this scenario. They include anti-inflammatory drugs, analgesics, anesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, bisphosphonates, calcium channel blockers and topical agents. NSAIDs showed no value in treating CRPS. Glucocorticoids are the only anti-inflammatory drugs for which there is direct clinical trial evidence in early stage of CRPS. Opioids are a reasonable second or third-line treatment option, but tolerance and long term toxicity are unresolved issues. The use of anticonvulsants and tricyclic antidepressants has not been well investigated for pain management in CRPS. During the last years, bisphosphonates have been the mostly studied pharmacologic agents in CRPS treatment and there are good evidence to support their use in this condition. Recently, the efficacy of intravenous (IV) administration of neridronate has been reported in a randomized controlled trial. Significant improvements in VAS score and other indices of pain and quality of life in patients who received four 100 mg IV doses of neridronate versus placebo were reported. These findings were confirmed in the open-extension phase of the study, when patients formerly enrolled in the placebo group received neridronate at the same dosage, and these results were maintained at 1 year follow-up. The current literature concerning sympathetic blocks and sympathectomy techniques lacks evidence of efficacy. Low evidence was recorded for a free radical scavenger, dimethylsulphoxide (DMSO) cream (50%). The same level of efficacy was noted for vitamin C (500 mg per day for 50 days) in prevention of CRPS in patients affected by wrist fracture. In conclusion, the best available therapeutic approach to CRPS is multimodal and is based on the use of several classes of drugs, associated to early physiotherapy. Neridronate at appropriate doses is associated with clinically relevant and persistent benefits in CRPS patients.

Project description:BACKGROUND: Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. METHODS: We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. RESULTS: Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs. CONCLUSIONS: miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.

Dataset Information

Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain.

Publications

Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain.

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