Project description: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.
Project description:we successfully identified pain-related genes through genome-wide expression profiling in blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p < 0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of 12 genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction. We focused on matrix metalloproteinase 9 (MMP9) that showed statistically significant difference from controls and the highest relative fold change in CRPS II patients to controls by qPCR validation (6.4 ± 2.47 times and p = 0.001). Identification of pain-related genes in peripheral blood of complex regional pain syndrome (CRPS) using cDNA microarray. Comparative gene expression profiles in peripheral blood of 5 healthy controls and 4 CRPS patients.
Project description:IntroductionComplex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments.MethodsThe literature regarding interventional treatments for CRPS has been systematically reviewed and summarized.ResultsBisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen.ConclusionsCRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.
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:we successfully identified pain-related genes through genome-wide expression profiling in blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p < 0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of 12 genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction. We focused on matrix metalloproteinase 9 (MMP9) that showed statistically significant difference from controls and the highest relative fold change in CRPS II patients to controls by qPCR validation (6.4 ± 2.47 times and p = 0.001).
Project description:BackgroundComplex regional pain syndrome (CRPS) is much more prevalent in women than men but potential differences in clinical phenotype have not been thoroughly explored to date. Differences in the clinical presentation between sexes may point at new avenues for a more tailored management approach of CRPS. We therefore explored if in CRPS, the patient's sex is associated with differences in clinical and psychological characteristics.MethodsIn this cross-sectional study of 698 CRPS patients (599 females) fulfilling the Budapest clinical or research criteria, CRPS signs and symptoms, CRPS severity, pain (average pain intensity in the previous week and McGill pain rating index), pain coping (Pain Coping Inventory), physical limitations (Radboud Skills Questionnaire (upper limb), Walking and Rising questionnaire (lower limb)), anxiety and depression (Hospital Anxiety and Depression scale) and kinesiophobia (Tampa scale for kinesiophobia) were evaluated.ResultsMale CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.ConclusionSex-related differences are present in CRPS, but the effect is generally small and mainly concerns psychological functioning. A greater awareness of sex-specific factors in the management of CRPS may contribute to achieving better outcomes.SignificanceWhat is known? Nonsex-specific clinical data of CRPS patients. What is new? Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.
Project description:IntroductionPatients with complex regional pain syndrome (CRPS) often show disturbed bone metabolism, assessed using three-phase bone scintigraphy (TPBS). However, current methods lack automation and standardisation. Bone serum markers have been proposed as biomarkers, but their utility is unclear.ObjectivesThis study aimed to evaluate bone metabolism in CRPS using TPBS and bone serum markers.MethodsA deep learning model for automated segmentation quantified tracer enhancement in TPBS images. Serum markers analysed included alkaline phosphatase (AP), 25-OH vitamin D, osteoprotegerin, procollagen type I N-terminal propeptide (PINP), and β-C-terminal telopeptide, compared to 48 healthy controls (HC). The study included 114 patients with CRPS, 41 of whom underwent TPBS.ResultsOf the 41 patients with CRPS with TPBS, 39 (95.1%) displayed radiotracer enhancement in the bone phase across CRPS subtypes. Serum markers of 114 patients did not significantly differ between patients and HC, nor did they correlate with TPBS enhancement, except in warm CRPS. In these patients, TPBS accumulation in the metacarpophalangeal region correlated with PINP (Spearman ρ = 0.63, P = 0.038), and AP levels were elevated at 78 U/L (interquartile range 64-88) compared to cold CRPS at 66 U/L (51-77; P = 0.003) and HC at 60 U/L (53-69; P < 0.001).ConclusionAutomated TPBS quantification revealed widespread bone metabolism alterations, common in CRPS and detectable beyond qualitative assessment. Although most serum markers remained unchanged, patients with warm CRPS exhibited unique features, suggesting distinct pathophysiological profiles. Integrating novel image analysis with other biomarkers may enhance diagnostic precision and patient stratification for targeted therapies.
Project description:BackgroundAberrant 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.MethodsWe 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.ResultsThree 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.ConclusionsmiRNA 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.
Project description: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.
Project description:BackgroundAllodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies.ObjectivesThis study investigated the use of pain-autonomic readouts to objectively detect sensitization processes in CRPS.MethodsTwenty individuals with chronic CRPS were recruited for the study alongside 16 age- and sex-matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand).ResultsIndividuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p < 0.001), but not in the control area (p > 0.05). Habituation of pinprick-induced SSRs was reduced in CRPS compared to HC in both the affected (p = 0.018) and slightly in the control area (p = 0.048). Habituation of heat-induced SSR was reduced in CRPS in the affected (p = 0.008), but not the control area (p = 0.053).ConclusionsThis is the first study demonstrating clinical evidence that pain-related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain-autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism-based treatment responses in clinical trials.SignificanceThis study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.