Analyzing marker substances for Complex Regional Pain Syndrome (CRPS)

Weniger als 5% der Patienten entwickeln Komplex-Regionales Schmerzsyndrom (CRPS) nach einem Trauma, insbesondere nach Frakturen. Es ist ein schmerzhaftes Syndrom, dass durch eine Vielzahl von klinischen Merkmalen gekennzeichnet ist. Es kann chronisch werden, wenn es nicht in den ersten Monaten kuriert wird. Wahrscheinlich spielen mehrere pathophysiologische Mechanismen eine Rolle in CRPS. Es wird vermutet, dass Neuropeptide und anti-inflammatorische Lipid-Mediatoren involviert sind. In dieser Arbeit wurden diese Moleküle in Hautbiopsien und Serum mit dem Ziel der Korrelation ihrer Konzentration mit klinischen Parametern mittels Massenspektrometrie (MS) untersucht. Hochauflösende und insbesondere NanoMS identifizierte Peptide und Fettsäuren im niederen fmol-Bereich. Die Methodik zeigte aber auch wenig Toleranz gegenüber dem chemischen Untergrund, so dass vornehmlich die robustere Kapillarchromatography eingesetzt wurde. Die Serum-Proteaseaktivität mit einem Fokus auf Angiotensin-konvertierendem Enzym (ACE) wurde untersucht. Bradykinin (BK) wurde zügig zu BK1-8 und BK1-5 abgebaut. Niedrigere BK1-5 Levels waren in Übereinstimmung mit der Hypothese verringerter ACE-Aktivität in CRPS.Less than 5% of patients develop Complex Regional Pain Syndrome (CRPS) after trauma, mostly after fractures. It is a painful syndrome characterized by a variety of clinical features including classical signs of inflammation and it can become chronical if not cured in the first few months. Likely, a number of pathophysiological mechanisms play a role in CRPS. The involvement of neuropeptides and anti-inflammatory lipid mediators has been suggested. Here, mass spectrometry (MS) was used to investigate these molecules in skin biopsies and serum with the aim of correlating their concentration with clinical parameters. High-end and in particular nanoscale MS identified peptides as well as fatty acids at the low fmol level. However, it also showed little tolerance for the chemical background so that a more robust capillary chromatography approach was preferentially used. Serum protease activity with a focus on angiotensin converting enzyme (ACE) was studied. Bradykinin (BK) was rapidly degraded to BK1-8 and BK1-5. The formation of lower BK1-5 levels was indicated in agreement with the hypothesis of reduced ACE-activity in CRPS

Local anaesthetic sympathetic blockade for complex regional pain syndrome

Local anaesthetic sympathetic blockade (LASB) is a common treatment for complex regional pain syndrome (CRPS). It involves blocking the activity of sympathetic nerves in the spine through the injection of a local anaesthetic drug. This updated review sought to identify the available evidence regarding whether LASB is effective at reducing pain in CRPS, how long any pain relief might last, and whether LASB is safe. We found a small number of small trials, all of which may be at risk of bias. We did not find evidence that LASB was better than placebo in reducing pain, or that it provided additional pain relief when added to rehabilitation. While a number of small studies compared LASB to other treatments, most did not find that LASB was better than any other intervention. Only five studies reported on adverse events. These studies reported only minor side effects but since most studies did not report this information we can draw no firm conclusions about the safety of LASB. Overall, while the evidence is very limited and precludes the drawing of strong conclusions, the existing evidence does not provide support for the efficacy of LASB in managing people with CRPS

Patterns of Sympathetic Responses Induced by Different Stress Tasks

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I)

Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group

Highlighting the Role of Biomarkers of Inflammation in the Diagnosis and Management of Complex Regional Pain Syndrome

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

Complex regional pain syndrome - phenotypic characteristics and potential biomarkers

Complex regional pain syndrome (CRPS) is a pain condition that usually affects a single limb, often following an injury. The underlying pathophysiology seems to be complex and probably varies between patients. Clinical diagnosis is based on internationally agreed-upon criteria, which consider the reported symptoms, presence of signs and exclusion of alternative causes. Research into CRPS biomarkers to support patient stratification and improve diagnostic certainty is an important scientific focus, and recent progress in this area provides an opportunity for an up-to-date topical review of measurable disease-predictive, diagnostic and prognostic parameters. Clinical and biochemical attributes of CRPS that may aid diagnosis and determination of appropriate treatment are delineated. Findings that predict the development of CRPS and support the diagnosis include trauma-related factors, neurocognitive peculiarities, psychological markers, and local and systemic changes that indicate activation of the immune system. Analysis of signatures of non-coding microRNAs that could predict the treatment response represents a new line of research. Results from the past 5 years of CRPS research indicate that a single marker for CRPS will probably never be found; however, a range of biomarkers might assist in clinical diagnosis and guide prognosis and treatment

Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system

BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. The main aim of the present study was to compare the sensitivity and specificity of calculation methods used to assess thermographic images (infrared imaging) obtained during temperature provocation. The secondary objective was to obtain information about the involvement of the sympathetic system in CRPS1. METHODS: We studied 12 patients in whom CRPS1 was diagnosed according to the criteria of Bruehl. High and low whole body cooling and warming induced and reduced sympathetic vasoconstrictor activity. The degree of vasoconstrictor activity in both hands was monitored using a videothermograph. The sensitivity and specificity of the calculation methods used to assess the thermographic images were calculated. RESULTS: The temperature difference between the hands in the CRPS patients increases significantly when the sympathetic system is provoked. At both the maximum and minimum vasoconstriction no significant differences were found in fingertip temperatures between both hands. CONCLUSION: The majority of CRPS1 patients do not show maximal obtainable temperature differences between the involved and contralateral extremity at room temperature (static measurement). During cold and warm temperature challenges this temperature difference increases significantly. As a result a higher sensitivity and specificity could be achieved in the diagnosis of CRPS1. These findings suggest that the sympathetic efferent system is involved in CRPS1

Mechanisms of toxic smoke inhalation and burn injury: Role of neutral endopeptidase and vascular leakage in mice

The effects of neutral endopeptidase (NEP) in acute inflammation in the lung were studied using a newly developed murine model of smoke and burn (SB) injury. C57BL/6 mice were pretreated with an i.v. dose of a specific NEP antagonist CGS-24592 (10 mg/Kg) 1 h prior to SB injury (n = 5–8/group). Mice were anesthetized with i.p. ketamine/xylazine, intubated, and exposed to cooled cotton smoke (2 × 30 s). After s.c. injection of 1 ml 0.9% saline, each received a 40% total body surface area (TBSA) flame burn. Buprenorphene (2 mg/kg) was given i.p. and resuscitated by saline. Evans Blue dye (EB) was injected i.v. 15 min before sacrifice. Lung wet/dry weight ratio was measured. After vascular perfusion, lungs were analyzed for their levels of EB dye and myeloperoxidase (MPO). In mice pretreated with CGS-24592 followed by SB injury the EB levels were significantly higher (61%, p = 0.043) than those with SB injury alone. There was a significant increase (144%, p = 0.035) in EB dye in animals with SB injury alone as compared to shams. In mice pretreated with CGS-24592 prior to SB injury wet/dry weight ratios were significantly (27%, p = 0.042) higher compared to animals with SB injury alone. CGS-24592 pretreatment also caused a significant increase in MPO (29%, p = 0.026) as compared to mice with SB injury alone. In conclusion the current study indicates that specific NEP inhibitor CGS 24592 exacerbates the SB-induced lung injury and inflammation in mice

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients