Abstract
Introduction
Complex regional pain syndrome (CRPS) is a neurological pain disorder that is challenging to diagnose and manage, resulting in increased morbidity and costs. It most commonly ...occurs following traumatic injury, such as a fracture, crush injury or surgery. Recent research has evaluated the efficacy of treatments which have contradicted previous hypotheses. This systematic review summarizes these findings to improve clinician’s decision-making.
Sources of data
A comprehensive search of PubMed, MEDLINE and Embase databases from inception through January 2021 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened relevant articles discussing the management of CRPS in adult trauma patients. All prospective and retrospective studies, non-randomized comparison studies and case series were considered for inclusion. Data extraction was performed by populating a predefined data abstraction sheet.
Areas of agreement
There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates, sympathectomy and brachial plexus blocks in the management of CRPS.
Areas of controversy
The latest evidence suggests that vitamin C has no significant role to play in the treatment or prevention of CRPS.
Growing points
A multidisciplinary team approach and early diagnosis are imperative for successful treatment of CRPS. The Budapest criteria and the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines should be used when diagnosing CRPS. There is currently no clear evidence of superiority in any treatment.
Areas timely for developing research
There are few high-quality studies that inform the best treatment modalities for CRPS. Though emerging treatments show promise, further research is needed.
Factors contributing to development of complex regional pain syndrome (CRPS) are not fully understood. This study examined possible epigenetic mechanisms that may contribute to CRPS after traumatic ...injury. DNA methylation profiles were compared between individuals developing CRPS (n = 9) and those developing non-CRPS neuropathic pain (n = 38) after undergoing amputation following military trauma. Linear Models for Microarray (LIMMA) analyses revealed 48 differentially methylated cytosine-phosphate-guanine dinucleotide (CpG) sites between groups (unadjusted P's < 0.005), with the top gene COL11A1 meeting Bonferroni-adjusted P < 0.05. The second largest differential methylation was observed for the HLA-DRB6 gene, an immune-related gene linked previously to CRPS in a small gene expression study. For all but 7 of the significant CpG sites, the CRPS group was hypomethylated. Numerous functional Gene Ontology-Biological Process categories were significantly enriched (false discovery rate-adjusted q value <0.15), including multiple immune-related categories (eg, activation of immune response, immune system development, regulation of immune system processes, and antigen processing and presentation). Differentially methylated genes were more highly connected in human protein-protein networks than expected by chance (P < 0.05), supporting the biological relevance of the findings. Results were validated in an independent sample linking a DNA biobank with electronic health records (n = 126 CRPS phenotype, n = 19,768 non-CRPS chronic pain phenotype). Analyses using PrediXcan methodology indicated differences in the genetically determined component of gene expression in 7 of 48 genes identified in methylation analyses (P's < 0.02). Results suggest that immune- and inflammatory-related factors might confer risk of developing CRPS after traumatic injury. Validation findings demonstrate the potential of using electronic health records linked to DNA for genomic studies of CRPS.
We investigated serum levels of 29 cytokines and immune-activated kynurenine and tetrahydrobiopterin pathway metabolites in 15 complex regional pain syndrome (CRPS) subjects and 14 healthy controls. ...Significant reductions in interleukin-37 and tryptophan were found in CRPS subjects, along with positive correlations between kynurenine/tryptophan ratio and TNF-α levels with kinesiophobia, tetrahydrobiopterin levels with McGill pain score, sRAGE, and xanthurenic acid and neopterin levels with depression, anxiety and stress scores. Using machine learning, we identified a set of binary variables, including IL-37 and GM-CSF, capable of distinguishing controls from established CRPS subjects. These results suggest possible involvement of various inflammatory markers in CRPS pathogenesis.
Display omitted
•Interleukin-37 and tryptophan levels are reduced in CRPS•Tetrahydrobiopterin levels correlate with pain scores in CRPS•Kynurenine/tryptophan ratio and TNF-α levels correlate with kinesiophobia in CRPS•Xanthurenic acid and neopterin levels correlate with psychological symptoms in CRPS•Biomarkers IL-37, GM-CSF, Tregs and CD8+ T cells can distinguish CRPS from controls
Purpose of Review
Complex regional pain syndrome (CRPS) refers to a chronic pain condition that is characterized by progressively worsening spontaneous regional pain without dermatomal distribution. ...The symptomatology includes pain out of proportion in time and severity to the inciting event. The purpose of this review is to present the most current information concerning epidemiology, diagnosis, pathophysiology, and therapy for CRPS.
Recent Findings
In recent years, discovery of pathophysiologic mechanisms of CRPS has led to significant strides in the understanding of the disease process.
Summary
Continued elucidation of the underlying pathophysiological mechanisms will allow for the development of more targeted and effective evidence-based therapy protocols. Further large clinical trials are needed to investigate mechanisms and treatment of the disorder.
Complex regional pain syndrome (CRPS) is a complex disorder that can have a significant impact on the quality of life of a person with this syndrome. The diagnosis and treatment of CRPS are often ...difficult as there is no one confirmatory test and no one definitive treatment. Currently, the most widely accepted clinical diagnostic criteria are the Budapest criteria, which were developed by expert consensus. Though no one single treatment has been found to be universally effective, early detection and an interdisciplinary approach to treatment appear to be key in treating CRPS. This review aims to present up-to-date clinical information regarding the diagnosis and management of CRPS and highlight the potential issues with diagnosis in the neurological population. Ultimately, more research is needed to identify the exact etiology of CRPS in order to help target appropriate therapies. In addition, more randomized controlled trials need to be performed in order to test new therapies or combinations of therapies, including pharmacological, interventional, and behavioral therapies, to determine the best treatment options for this potentially debilitating disorder.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Complex regional pain syndrome (CRPS) is a chronic pain condition associating sensory, motor, trophic and autonomic symptoms in one limb. Cognitive difficulties have also been reported, affecting the ...patients' ability to mentally represent, perceive and use their affected limb. However, the nature of these deficits is still a matter of debate. Recent studies suggest that cognitive deficits are limited to body-related information and body perception, while not extending to external space. Here we challenge that statement, by using temporal order judgment (TOJ) tasks with tactile (i.e. body) or visual (i.e. extra-body) stimuli in patients with upper-limb CRPS. TOJ tasks allow characterizing cognitive biases to the advantage of one of the two sides of space. While the tactile TOJ tasks did not show any significant results, significant cognitive biases were observed in the visual TOJ tasks, affecting mostly the perception of visual stimuli occurring in the immediate vicinity of the affected limb. Our results clearly demonstrate the presence of visuospatial deficits in CRPS, corroborating the cortical contribution to the CRPS pathophysiology, and supporting the utility of developing rehabilitation techniques modifying visuospatial abilities to treat chronic pain.
Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features. Few treatments have proven effective, in part, because of a historically poor understanding ...of the mechanisms underlying the disorder. CRPS research largely conducted during the past decade has substantially increased knowledge regarding its pathophysiologic mechanisms, indicating that they are multifactorial. Both peripheral and central nervous system mechanisms are involved. These include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. Relative contributions of the mechanisms underlying CRPS may differ across patients and even within a patient over time, particularly in the transition from "warm CRPS" (acute) to "cold CRPS" (chronic). Enhanced knowledge regarding the pathophysiology of CRPS increases the possibility of eventually achieving the goal of mechanism-based CRPS diagnosis and treatment.
Complex regional pain syndrome (CRPS) is characterized by continuous pain that is often accompanied by sensory, motor, vasomotor, sudomotor, and trophic disturbances. If left untreated, it can have a ...significant impact on the quality of life of patients. The diagnosis of CRPS is currently based on a set of relatively subjective clinical criteria: the New International Association for the Study of Pain clinical diagnostic criteria for CRPS. There are still no objective laboratory tests to diagnose CRPS and there is a great need for simple, objective, and easily measurable biomarkers in the diagnosis and management of this disease. In this review, we discuss the role of inflammation in the multi-mechanism pathophysiology of CRPS and highlight the application of potential biomarkers of inflammation in the diagnosis and management of this disease.
Research into complex regional pain syndrome (CRPS) has made significant progress. First, there was the implementation of the official IASP "Budapest" diagnostic criteria. It would be desirable to ...also define exclusion and outcome criteria that should be reported in studies. The next step was to recognize the complex pathophysiology. After trauma, some inflammation is physiological; in acute CRPS, this inflammation persists for months. There is an abundance of inflammatory and a lack of anti-inflammatory mediators. This proinflammatory network (cytokines and probably also other mediators) sensitizes the peripheral and spinal nociceptive system, it facilitates the release of neuropeptides from nociceptors inducing the visible signs of inflammation, and it stimulates bone cell or fibroblast proliferation, and endothelial dysfunction leading to vascular changes. Trauma may also expose nervous system structures to the immune system and triggers autoantibodies binding to adreno- and acetylcholine receptors. In an individual time frame, the pain in this inflammatory phase pushes the transition into "centralized" CRPS, which is dominated by neuronal plasticity and reorganization. Sensory-motor integration becomes disturbed, leading to a loss of motor function; the body representation is distorted leading to numbness and autonomic disturbances. In an attempt to avoid pain, patients neglect their limb and learn maladaptive nonuse. The final step will be to assess large cohorts and to analyze these data together with data from public resources using a bioinformatics approach. We could then develop diagnostic toolboxes for individual pathophysiology and select focused treatments or develop new ones.
Chronic regional pain syndrome (CRPS) is an inflammatory and neuropathic pain disorder characterized by the involvement of the autonomic nervous system with sensory, autonomic, motor, skin, and bone ...changes. At present, universally accepted consensus criteria for CRPS are not yet established, despite the diagnostic criteria proposed by the International Association for the Study of Pain (IASP). Various hypotheses for the pathophysiology of CRPS have been proposed; as a result, current therapeutic modalities are varied. General epidemiological data on CRPS are necessary for effective management. However, recent data on the epidemiology of CRPS in Korea are scarce. The aim of this study was to evaluate the incidence and other epidemiological features of CRPS in the general population in Korea. In this study on the epidemiology of CRPS in Korea, population-based medical data acquired from 51,448,491 subscribers to the National Health Insurance Service (NHIS) from 2011 to 2015 were analyzed, including the incidence, distribution by the CRPS type, regional distribution, monthly distribution, medical costs, and healthcare resource-utilization. The findings indicated that the incidence of CRPS in Korea was 29.0 per 100,000 person-years in 2015 and was correlated with patient age and sex. CRPS types included type I (63%) and type II (37%); moreover, the number of individuals with CRPS I have shown a growing trend since 2011. There was no monthly distribution, but there was regional variation according to the province. The medical departments managing CRPS I the most were orthopedics, internal medicine, anesthesiology and pain medicine, in order; however, patients with CRPS spent more money per visit in the departments of rehabilitation medicine, and anesthesiology and pain medicine. The incidence rate of CRPS in Korea was 29.0 per 100,000 person-years with an increasing trend, which was correlated with patient age in the 70s and female sex. CRPS type I was more common than CRPS type II; in addition, constant increase in medical expenses, regional imbalance, and differences in medical expense among medical specialties should be considered for early management of patients to reduce the disease burden in Korea. Sharing of knowledge about the diagnostic criteria of CRPS are also needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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