Periphere Mechanismen von Gelenkschmerzen mit speziellem Fokus auf den synovialen Fibroblasten

Zusammenfassung: Gelenkschmerz ist eine der am häufigsten auftretenden Schmerzformen. Etwa ein Drittel der Bevölkerung hat bereits einmal Gelenkschmerz erfahren. Bis heute ist diese Schmerzform nicht effektiv behandelbar, und Nebenwirkungen der verwendeten Medikamente sind häufig gefährlich. Es ist deshalb sehr wichtig, unser Verständnis über die Ursachen und die Mechanismen von Gelenkschmerzen weiter zu verbessern. Gelenke und ihre umgebenden Strukturen sind sehr gut mit Nervenfasern versorgt, die auf mechanische Beanspruchung reagieren. Lokale Entzündungsprozesse sensibilisieren diese Afferenzen, und es resultiert eine erniedrigte Schmerzschwelle. Über die lokalen Prozesse, insbesondere im Synovialgewebe, ist wenig bekannt. Rezeptoren, die im Nervensystem beschrieben sind, werden zunehmend auch im synovialen Fibroblasten nachgewiesen. Deren Funktion ist noch weitgehend unbekannt. Allerdings sind neue therapeutische Angriffspunkte über andere Systeme, z.B. den TRPV1- oder den P2X4-Rezeptor, zu erwarte

Ist die Fibromyalgie eine Viruserkrankung?

Zusammenfassung: Sind Viren verantwortlich für den Schmerz bei Patienten mit Fibromyalgie? Sind Viren der Auslöser der rheumatoiden Arthritis? Ist das "chronic fatigue syndrome" eine Viruserkrankung? Viele offene Fragen - wenig oder kontroverse Antworten. Nach derzeitiger Kenntnis über die Entstehung des Schmerzes bei der Fibromyalgie lösen sowohl periphere als auch zentrale Mechanismen die "bunte" Symptomatik der Fibromyalgie aus. Trotz ihres weiten Symptomspektrums handelt es sich bei der Erkrankung jedoch um eine spezifische Entität, die hauptsächlich mit dualen Wiederaufnahmehemmern, Antikonvulsiva, Tramadol, selektiven Serotoninwiederaufnahmehemmern, Gammahydroxybutyrat und Dopaminagonisten in individuell sinnvoller Kombination zu behandeln is

ALL TUNA IS NOT CREATED EQUAL: THE EXISTENCE OF QUANTITY SURCHARGES DUE TO PRODUCT DIFFERENTIATION.

Quantity surcharges exist when unit prices are higher for larger packages. We hypothesize that various sizes of goods are differentiated products, and this explains some surcharges. Estimating a random-coefficients logit demand model, we examine own and cross elasticities to determine the level of differentiation between products with different size packages.Marketing,

Geometric and dynamic perspectives on phase-coherent and noncoherent chaos

Statistically distinguishing between phase-coherent and noncoherent chaotic dynamics from time series is a contemporary problem in nonlinear sciences. In this work, we propose different measures based on recurrence properties of recorded trajectories, which characterize the underlying systems from both geometric and dynamic viewpoints. The potentials of the individual measures for discriminating phase-coherent and noncoherent chaotic oscillations are discussed. A detailed numerical analysis is performed for the chaotic R\"ossler system, which displays both types of chaos as one control parameter is varied, and the Mackey-Glass system as an example of a time-delay system with noncoherent chaos. Our results demonstrate that especially geometric measures from recurrence network analysis are well suited for tracing transitions between spiral- and screw-type chaos, a common route from phase-coherent to noncoherent chaos also found in other nonlinear oscillators. A detailed explanation of the observed behavior in terms of attractor geometry is given.Comment: 12 pages, 13 figure

Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes

Objectives. To provide an overview of the effectiveness of multidisciplinary treatments of chronic pain and investigate about their differential effects on outcome in various pain conditions and of different multidisciplinary treatments, settings or durations. Methods. In this article, the authors performed a systematic review of all currently available randomized controlled trials (RCTs) fulfilling the inclusion criteria, by using a recently developed rating system aimed to assess the strength of evidence with regard to the methodological quality of the trials. Results. Compared with other non-disciplinary treatments, moderate evidence of higher effectiveness for multidisciplinary interventions was shown. In contrast to no treatment or standard medical treatment, strong evidence was detected in favour of multidisciplinary treatments. The evidence that comprehensive inpatient programmes were more beneficial that outpatient programmes was moderate. Fibromyalgia and chronic back pain patients tended to profit more substantially than patients with diverse origins or chronic pain diagnoses. No evidence was found that treatment variables, such as duration or programme components, were influential for the success of the intervention. Conclusion. A standard of multidisciplinary programmes should be internationally established to guarantee generally good outcomes in the treatment of chronic pain. Our results highlight the lack of quality of design, execution or reporting of many of the RCTs included in this article. Future studies should more specifically focus on differential effects of treatment components and patient variables, allowing the identification of subgroups, which most probably would profit from multidisciplinary pain programme

The impact of asking intention or self-prediction questions on subsequent behavior: a meta-analysis

The current meta-analysis estimated the magnitude of the impact of asking intention and self-prediction questions on rates of subsequent behavior, and examined mediators and moderators of this question–behavior effect (QBE). Random-effects meta-analysis on 116 published tests of the effect indicated that intention/prediction questions have a small positive effect on behavior (d+ = 0.24). Little support was observed for attitude accessibility, cognitive dissonance, behavioral simulation, or processing fluency explanations of the QBE. Multivariate analyses indicated significant effects of social desirability of behavior/behavior domain (larger effects for more desirable and less risky behaviors), difficulty of behavior (larger effects for easy-to-perform behaviors), and sample type (larger effects among student samples). Although this review controls for co-occurrence of moderators in multivariate analyses, future primary research should systematically vary moderators in fully factorial designs. Further primary research is also needed to unravel the mechanisms underlying different variants of the QBE

Analgesic action of acetaminophen in symptomatic osteoarthritis of the knee

Objectives. The study was designed to investigate the analgesic effects and mechanisms of acetaminophen (paracetamol) in symptomatic osteoarthritis (OA) of the knee. Methods. Twenty patients with symptomatic OA were randomly allocated to two groups treated with either acetaminophen or rofecoxib for 3 months. Visits and measurements were scheduled upon entry (T0), at month 1 (T1) and at month 3 (T3). The intensity of joint pain was evaluated with a 100-mm visual analogue scale (VAS). The physical function of the affected knee was evaluated with a questionnaire comparable to the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Levels of serotonin, substance P (SP) and β-endorphin (BEND) were determined with commercial enzyme-linked immunoassay kits. The expression of κ opioid receptor (KOR) in peripheral mononuclear blood cells (PBMCs) was quantified by real-time PCR. Results. Both acetaminophen and rofecoxib relieved pain considerably but with different kinetics, and affected different biomarkers. Rofecoxib appeared to be more efficient, reducing pain intensity by 56% at T1 (P<0.01), whereas acetaminophen reduced it by only 29%. Physical function improved in both groups by T3. Correlated with the pain relief, acetaminophen significantly reduced plasma BEND levels, whereas rofecoxib did not do so. In both groups plasma SP levels were elevated compared with T0. A reduction in serum serotonin was detected in the rofecoxib group at T1 (P=0.004) but had recovered at T3. No changes in KOR mRNA in PBMCs were observed in either group. Conclusions. There is a correlation between reduction in circulating BEND and OA pain relief in patients treated with acetaminophe

Analgesic action of acetaminophen in symptomatic osteoarthritis of the knee

Objectives. The study was designed to investigate the analgesic effects and mechanisms of acetaminophen (paracetamol) in symptomatic osteoarthritis (OA) of the knee. Methods. Twenty patients with symptomatic OA were randomly allocated to two groups treated with either acetaminophen or rofecoxib for 3 months. Visits and measurements were scheduled upon entry (T0), at month 1 (T1) and at month 3 (T3). The intensity of joint pain was evaluated with a 100-mm visual analogue scale (VAS). The physical function of the affected knee was evaluated with a questionnaire comparable to the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Levels of serotonin, substance P (SP) and β-endorphin (BEND) were determined with commercial enzyme-linked immunoassay kits. The expression of κ opioid receptor (KOR) in peripheral mononuclear blood cells (PBMCs) was quantified by real-time PCR. Results. Both acetaminophen and rofecoxib relieved pain considerably but with different kinetics, and affected different biomarkers. Rofecoxib appeared to be more efficient, reducing pain intensity by 56% at T1 (P<0.01), whereas acetaminophen reduced it by only 29%. Physical function improved in both groups by T3. Correlated with the pain relief, acetaminophen significantly reduced plasma BEND levels, whereas rofecoxib did not do so. In both groups plasma SP levels were elevated compared with T0. A reduction in serum serotonin was detected in the rofecoxib group at T1 (P=0.004) but had recovered at T3. No changes in KOR mRNA in PBMCs were observed in either group. Conclusions. There is a correlation between reduction in circulating BEND and OA pain relief in patients treated with acetaminophe

Persistent Chaos in High Dimensions

An extensive statistical survey of universal approximators shows that as the dimension of a typical dissipative dynamical system is increased, the number of positive Lyapunov exponents increases monotonically and the number of parameter windows with periodic behavior decreases. A subset of parameter space remains in which topological change induced by small parameter variation is very common. It turns out, however, that if the system's dimension is sufficiently high, this inevitable, and expected, topological change is never catastrophic, in the sense chaotic behavior is preserved. One concludes that deterministic chaos is persistent in high dimensions.Comment: 4 pages, 3 figures; Changes in response to referee comment