Complex Regional Pain Syndrome: An inflammatory disease

The pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS. Therefore, some immunological aspects were further explored with the aim to achieve more insight in both the pathophysiology and possible treatment options in CRPS. The main results: 1. In contrast to what is generally assumed, inflammation may be involved in patients with cold CRPS. 2. The prevalence of antinuclear antibodies (ANA) is significantly higher in CRPS patients than in the healthy population. The prevalence of anti-neuronal antibodies however does not deviate from that in the healthy population. Striking is the fact that the prevalence of ANA was more similar to that observed in patients with an autoimmune disease such as rheumatoid arthritis than that in patients with a classic autoimmune disease. This is a relevant finding because it may affect the choice of treatment. 3. The current empirical evidence for the efficacy of administering the most commonly used immunomodulating medication (i.e. glucocorticoids, TNF-α antagonists, thalidomide, bisphosphonates, and immunoglubulins) is scarce. 4. To test the assumption that TNF-α antagonists can reduce the manifestation of inflammation in CRPS, a double-blind randomized placebo-controlled trial was conducted. Unfortunately, this study was terminated before the required number of patients for sufficient statistical power had been reached. Nevertheless, the limited data showed a trend towards a greater reduction of TNF-α in the intervention group compared with the placebo group. 5. Mast cells are known to be involved in the inflammatory process of CRPS and also play a role in the process of central sensitization. In the development of a more mechanism-based treatment of CRPS, influencing the activity of mast cells might be important

Effect of sputtering power on friction coefficient and surface energy of co-sputtered titanium and molybdenum disulfide coatings and its performance in micro hot-embossing

Si micromolds are common for fabrication of polymer-based microfluidic devices by hot-embossing because of the well established fabrication methods for Si, e.g., deep reactive ion etching, for favorable surface finish and accuracy. The problems with low yield, poor reproducibility, premature failure and limited lifetime of a Si micromold are induced by high friction and surface adhesion generated during demolding. Therefore, Titanium (Ti) and molybdenum disulfide (MoS[subscript 2]) coatings were deposited on Si micromolds via magnetron co-sputtering at various combinations of target powers to improve its surface properties. Coating composition, crystallographic orientation, roughness, critical load, hardness, friction coefficient and surface energy were measured by X-ray photoelectron spectroscopy, X-ray diffraction, atomic force microscopy, scratch testing, nanoindentation, ball-on-disc tribometry and the contact angle method respectively. A statistical design of experiment matrix was used to investigate the effect of the Ti and MoS[subscript 2] target powers on the friction coefficient and surface energy of the coatings. From this designed experiment, it was observed that increasing MoS[subscript 2] target power was associated with increasing surface energy and decreasing friction coefficient and target powers had statistically significant effects on these parameters. Crystallinity, roughness and hardness of the coatings increased with increasing Ti concentration. A mathematical model of the effects of Ti and MoS[subscript 2] target powers on the friction coefficient and surface energy of the coatings has been fit to the experimental results using the response surface method. Uncoated and MoS[subscript 2]–Ti coated Si micromolds were used in hot-embossing for a comparative study on replication performance of uncoated and various coated micromolds. Hotembossed PMMA microstructures showed that coating improve replication performance of Si micromolds. Si micromold coated with co-sputter of Ti and MoS[subscript 2] at power of 300 and 75 W respectively, showed better replication quality among the selected target powers

Morphology and function of Bast’s valve: additional insight in its functioning using 3D-reconstruction

The utriculo-endolymphatic valve was discovered by Bast in 1928. The function of Bast’s valve is still unclear. By means of orthogonal-plane fluorescence optical sectioning (OPFOS) microscopy 3D-reconstructions of the valve and its surrounding region are depicted. The shape of the duct at the utricular side is that of a flattened funnel. In the direction of the endolymphatic duct and sac this funnel runs into a very narrow duct. The valve itself has a rigid ‘arch-like’ configuration. The opposing thin, one cell-layer thick, utricular membrane is highly compliant. We propose that opening and closure of the valve occurs through movement of the flexible base/utricular membrane away from and toward the relatively rigid valve lip

The prevalence of autoantibodies in complex regional pain syndrome type i

Autoimmunity has been suggested as one of the pathophysiologic mechanisms that may underlie complex regional pain syndrome (CRPS). Screening for antinuclear antibodies (ANA) is one of the diagnostic tests, which is usually performed if a person is suspected to have a systemic autoimmune disease. Antineuronal antibodies are autoantibodies directed against antigens in the central and/or peripheral nervous system. The aim of this study was to compare the prevalence of these antibodies in CRPS patients with the normal values of those antibodies in the healthy population. Twenty seven (33%) of the 82 CRPS patients of whom serum was available showed a positive ANA test. This prevalence is significantly higher than in the general population. Six patients (7.3%) showed a positive result for typical antineuronal antibodies. This proportion, however, does not deviate from th

Variability in Blood Pressure Assessment in Patients Supported with the HeartMate 3TM

Targeted blood pressure (BP) control is a goal of left ventricular assist device medical management, but the interpretation of values obtained from noninvasive instruments is challenging. In the MOMENTUM 3 Continued Access Protocol, paired BP values in HeartMate 3 (HM3) patients were compared from arterial (A)-line and Doppler opening pressure (DOP) (319 readings in 261 patients) and A-line and automated cuff (281 readings in 247 patients). Pearson (R) correlations between A-line mean arterial (MAP) and systolic blood pressures (SBP) were compared with DOP and cuff measures according to the presence (\u3e1 pulse in 5 seconds) or absence of a palpable radial pulse. There were only moderate correlations between A-line and noninvasive measurements of SBP (DOP R = 0.58; cuff R = 0.47) and MAP (DOP R = 0.48; cuff R = 0.37). DOP accuracy for MAP estimation, defined as the % of readings within ± 10 mmHg of A-line MAP, decreased from 80% to 33% for DOP ≤ 90 vs. \u3e90 mmHg, and precision also diminished (mean absolute difference [MAD] increased from 6.3 ± 5.6 to 16.1 ± 11.4 mmHg). Across pulse pressures, cuff MAPs were within ±10 mmHg of A-line 62.9%-68.8% of measures and MADs were negligible. The presence of a palpable pulse reduced the accuracy and precision of the DOP-MAP estimation but did not impact cuff-MAP accuracy or precision. In summary, DOP may overestimate MAP in some patients on HM3 support. Simultaneous use of DOP and automated cuff and radial pulse may be needed to guide antihypertensive medication titration in outpatients on HM3 support

Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p < 0 001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

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