[Seeing others is believing-analgesic placebo effects through observational learning?] / Seeing others is believing ­ Analgetische Placeboeffekte durch Beobachtungslernen?

BACKGROUND: There are many studies on placebo analgesia and its underlying mechanisms that show a significant improvement of care for chronic pain patients. However, observational learning has not been researched to this degree. OBJECTIVES: The goal of this work is to provide an overview of the research on placebo analgesia via observational learning. The evidence around whether observational learning can induce placebo analgesia will be discussed. Also, research on the factors that influence observational learning of placebo analgesia will be reviewed. MATERIALS AND METHODS: To this end, research data bases were searched for studies on placebo analgesia via observational learning. RESULTS: After inclusion and exclusion criteria were implemented, 12 studies remained. To date, there has been only one study with patients with chronic pain. The small number of included studies do not permit universal statements. However, there is preliminary evidence that observation triggers placebo analgesia as an independent mechanism. Observational learning in an experimental setting can induce placebo effects. Attention focusing on the observation might be critical. The effect sizes tend to be small to large. The effect of classical conditioning and observational learning seem to be of equal size. Live models, video recordings and even pictures of models also induce similar effects. Observational learning induces a change in expectation. DISCUSSION: The evidence included provides the theoretical basis for potential significant clinical impact. Further research is needed to extend these findings to chronic pain patients.

[Placebo effects in pain therapy]. / Placeboeffekte in der Schmerztherapie.

In the past few decades, research on pain and placebo analgesia has gained importance both scientifically and clinically. In this article, the current findings and focus of research as well as the significance of placebo research for assessing the effectiveness of pain medication are illustrated. The underlying mechanisms of placebo analgesia not only have implications for theoretical models but also offer clinically relevant guidelines for everyday interventions in pain treatment. However, many placebo phenomena are not fully understood and have to be investigated further in order to exploit the full potential of placebo effects. Interindividual differences and their inclusion in treatment will play a major role in this aspect.

[Psychological factors in the context of perioperative knee and joint pain: the role of treatment expectations in pain evolvement]. / Psychologische Faktoren im Kontext perioperativer Knie- und Gelenkschmerzen: die Rolle der Behandlungserwartungen für den Schmerzverlauf.

Chronic knee and joint pain, like all chronic pain, is a complex multidimensional event that involves somatic, psychological and social factors. Patients with knee and other joint pain experience limited mobility in their daily lives, in their professional and personal activities, and in their leisure physical exercise activities. Pain increasingly prevents them from achieving their goals. Psychological factors not only interact with neurobiological and immunological processes of pain, they play an important role in the development and maintenance of pain. Within that, expectations concerning the course of the disease and its treatment play a significant role. Study designs involving a placebo knee surgery show the high influence of these variables. The patients receiving the verum surgery do not report-as expected-less pain or better functioning than those receiving a placebo surgery. This significant influence of psychological factors may be clinically relevant. A positive patient-staff relationship-characterized by trust, warmth and empathy-is essential in order to achieve optimal therapeutic efficacy of a treatment. Every surgeon, pain physician, pain psychologist or pain physiotherapist is responsible for establishing a trusting interpersonal relationship between themselves and their patients.

The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section-a systematic review and meta-analysis.

Neuraxial clonidine improves postoperative analgesia in the general surgical population. The efficacy and safety of neuraxial clonidine as a postoperative analgesic adjunct in the Caesarean section population still remains unclear. This systematic review and meta-analysis aims to evaluate the effect of perioperative neuraxial clonidine on postoperative analgesia in women having Caesarean section under neuraxial anaesthesia. We included randomized controlled trials comparing the analgesic efficacy of the perioperative administration of neuraxial clonidine alone or in combination with a local anaesthetic and/or opioids in women having elective Caesarean section under neuraxial anaesthesia when compared with placebo. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched until February 2017. Eighteen studies were included in the meta-analysis. Neuraxial clonidine reduced 24 h morphine consumption [mean difference (MD): -7.2 mg; 95% confidence interval (CI): -11.4, -3.0 mg; seven studies] and prolonged time to first analgesic request (MD: 135 min; 95% CI: 102, 168 min; 16 studies) when compared with the control group. Neuraxial clonidine increased intraoperative hypotension [odds ratio (OR): 2.849; 95% CI: 1.363, 5.957], intraoperative sedation (OR: 2.355; 95% CI: 1.016, 5.459), but reduced the need for intraoperative analgesic supplementation (OR: 0.224; 95% CI: 0.076, 0.663). The effect of clonidine on intraoperative bradycardia, intraoperative and postoperative nausea and vomiting, postoperative sedation, and pruritus were inconclusive. Neuraxial clonidine did not negatively impact neonatal umbilical artery pH or Apgar scores. This review demonstrates that neuraxial clonidine enhances postoperative analgesia in women having Caesarean section with neuraxial anaesthesia, but this has to be balanced against increased maternal adverse effects.

Suitability of Wild Boar (Sus scrofa) as a Bioindicator for Environmental Pollution with Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS).

Wildlife species, such as roe deer, moose, brown hare, wild boar, etc., are known to accumulate persistent environmental contaminants and thus are useful as bioindicators for environmental pollution. Wild boars become exposed to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from flora, fauna, water, and soil. The main exposure pathway to PFOA and PFOS is assumed to be the oral intake. From studies in domestic pigs (belonging to the same species Sus scrofa), it has been established that the oral exposure results in the liver accumulation of PFOA and PFOS. Thus, we posit that wild boars can be quantitatively used as suitable bioindicators for the presence of these substances in the environment. After the environmental pollution case in the Hessian region Sauerland in 2006, monitoring programs of individual Federal States from 2007 to 2013 showed that almost all wild boar liver samples contained PFOA and PFOS. In 2014, the analyses of PFOA and PFOS in liver of wild boars hunted in the south, north, and west of Germany showed liver concentrations at the same level among regions. Overall, an average ratio of PFOS:PFOA concentration in liver of 20.5:1 was found. To estimate the actual ratio of PFOS:PFOA in the wild boars' dietary exposure, we performed toxicokinetic modeling. According to the model, the PFOS exposure is only 2.2 times that of PFOA (because PFOS has slower elimination kinetics and higher affinity for the liver than PFOA). Overall, the determination of PFOA and PFOS in liver of wild boars indicates that both substances are ubiquitously distributed in the environment. At the same time, higher exposures were found for animals living in closer proximity to dense human populations.

[Placebo response - Mechanisms and clinical applications]. / Placeboreaktion ­ Mechanismen und klinische Anwendungen.

Research on placebo responses has made major progress in recent years. Placebo responses are psychobiological events, which are created by the entire therapeutic context. They can appear at any time, not only in experimental and clinical settings. Several studies on analgesia-related placebo research showed that patients have higher placebo responses in comparison to healthy participants, which may also last longer. Expectations play a key role in placebo analgesia. They can be induced via three central psychological mechanisms: 1) expectation induced via instructions, 2) expectation induced via classical conditioning and 3) expectation induced via social learning. These mechanisms are controlled by neurobiological structures and modulate pain perception resulting in pain relief by positive expectations and increased pain by negative expectations, the so-called nocebo effect. There is an ongoing discussion that these psychological mechanisms may also play a central role in inducing and maintaining itch-reducing placebo responses. The current state of research suggests that placebo responses could be used in clinical contexts and should not be viewed as being in competition with medications but as an additive increase in efficacy of a pharmacological substance through specifically induced placebo responses. This targeted use is also possible within ethical guidelines. Important prerequisites are that the research results can be transferred from healthy participants to patients and that the placebo responses are reproducible.

[Psychological treatments for pain in cancer patients : A systematic review on the current state of research]. / Schmerzpsychologische Interventionen bei onkologischen Patienten : Ein systematisches Review zum aktuellen Stand der Forschung.

BACKGROUND: In cancer patients, pain is one of the main symptoms and especially in the late stages of disease, these symptoms can be associated with considerable suffering. In psycho-oncology, preliminary psychological therapies targeting cancer pain have been tested; however, a systematic review of available interventions is lacking, especially considering their dissemination, evidence base, study quality, and the comparison with established treatments. Therefore, the aim of the current study is to systematically review the current research on psychological treatments for pain in cancer patients. MATERIALS AND METHODS: During May 2014, MEDLINE, PsycINFO, PSYNDEX, and CENTRAL databases were searched. Psychological treatments for pain in adult cancer patients studied in randomized, controlled trials (RCTs) and referring to pain as primary or secondary outcome were included. After examination for inclusion, structured data extraction and assessment followed. Data were synthesized narratively. RESULTS: In the review, 32 RCTs were included. Studies mainly referred to patients with breast cancer or patients in earlier stages of the disease. The methodological quality of included studies was heterogeneous. Most commonly, short interventions were delivered by nurses in out-patient settings. Interventions including education and relaxation techniques were utilized most often, followed by interventions with behavioral or cognitive components. CONCLUSION: A need for research persists regarding efficacy of current psychotherapeutic interventions, or the role of mediator variables (e. g., coping) on pain perception in cancer patients. Studies with high methodological quality which comprehensively and transparently report on interventions and designs are lacking.

[Effects of interdisciplinary functional restoration treatment with cognitive behavior therapy in patients with chronic back pain: healthcare research in the context of selective contracts]. / Effekte eines interdisziplinären Functional-restoration-Behandlungsprogramms mit kognitiv-behavioraler Therapie beim chronischen Rückenschmerz : Versorgungsforschung im Kontext von Selektivverträgen.

INTRODUCTION: The efficacy of functional restoration programs for the treatment of chronic back pain is well documented. Nevertheless, there are only a few such centres in Germany and few trials have been conducted in German-speaking regions to demonstrate that implementing such programs in everyday clinical settings with large numbers of patients is just as effective as in a research setting. The present study examined whether the positive effects of such programs can also be observed in the clinically relevant context of a standardized day clinic treatment regimen. MATERIAL AND METHODS: A total of 681 back pain patients in 2 German cities were examined at 4 measurement points (before and immediately after the program, as well as 6 and 12 months after treatment) using a comprehensive questionnaire on perceived pain and symptoms of anxiety and depression, as well as the work situation. RESULTS: In both cities significant and long-term improvements in back pain, pain-related impairment and degree of chronification were observed, as well as a high return-to-work rate after treatment. Hence, the quality of such programs was also confirmed for a large patient population.

Prevention of intradialytic hypotension in patients with acute kidney injury submitted to sustained low-efficiency dialysis.

OBJECTIVES: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). METHODS: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0°C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5°C with a variable sodium concentration [150-138 mEq/L] and UF rate. RESULTS: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 ± 1.25 L vs. 1.59 ± 1.03 L in control, p = 0.04) when compared with control group. CONCLUSIONS: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

[Comparative psychological aspects of itching and pain]. / Vergleichende psychologische Aspekte von Juckreiz und Schmerz.

Itching is a major symptom of chronic skin diseases such as atopic dermatitis and leads to considerable psychological strain. Chronic itching lowers patient's quality of life similar to chronic pain and influences the medical treatment. The frequently resulting scratching behavior (short-term avoidance of itch) leads to continuation and exacerbation of the disease, just as with specific pain behavior. For the development of itching and pain psychosocial factors have been identified in addition to somatic ones. However, recent data suggest that there is a complex interaction between pain and itching and comparable mechanisms of neuronal sensitization. In contrast to traditional biomedical one-dimensional models which focus mainly on physical and not psychological factors of a disease, recent data support a biopsychosocial model of development and maintenance for itching and pain. Biopsychosocial understanding of a disease should consequently be taken as the basis for treatment and the importance of interdisciplinary treatment is emphasized. This article will focus on chronic itching and pain with particular consideration of psychological factors.

[Measures of success in treatment of chronic back pain: pain intensity, disability and functional capacity: determinants of treatment success in multimodal day clinic setting]. / Vorhersage verschiedener Erfolgsmaße in der Behandlung chronischer Rückenschmerzen: Schmerzintensität, Beeinträchtigung und Funktionskapazität: Determinanten des Behandlungserfolges in einem tagesklinischen multimodalen Setting.

INTRODUCTION: The empirical findings on risk factors for a favorable/unfavorable outcome upraised via pain intensity, disability and functional capacity after empirically well-evaluated multimodal treatment are inconsistent. The objective of this study was to analyze the relevance of psychosocial and pain-related variables for therapeutic outcome in an unselected sample of patients with chronic non-specific back pain (CBP). METHODS: Included were 681 patients with CBP referred to an outpatient-based multidisciplinary pain rehabilitation program and 320 took part in a survey 12 months later. Before, directly after and 12 months after the program the patients received a questionnaire which contained pain-related items on pain intensity, disability, self-reported functional capacity which were defined as outcome variables, psychological items (anxiety, depression) and work-related items which represented probable predictor variables. Multivariable regression analyses were calculated to estimate the contribution of the selected parameters on pain intensity, disability and functional capacity. RESULTS: The calculated regressions showed only a moderate ability to predict or explain the outcomes pain intensity, disability and functional capacity. However, depression and body mass index (BMI) were significantly related to pain-related therapeutic outcome.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2 MCF7 cell line after paclitaxel reflecting the observed increase in senescence. CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.

Treatment history and placebo responses to experimental and clinical pain in chronic pain patients.

BACKGROUND: Placebo analgesia refers to the reduction in pain due to the administration of an inert treatment. It is induced by expectations of pain relief which are enhanced by learning mechanisms. In healthy humans, prior positive experiences enhance the placebo response. However, the effects of patients' prior experiences with treatment on placebo responses have not yet been examined. This study investigated how verbal information, learning and treatment history influence the magnitude of placebo analgesia in chronic pain. METHODS: We administered a pharmacological placebo intervention in a sample of chronic pain patients (n = 49) who were seeking treatment in an outpatient pain clinic. Analyses were based on placebo responders. RESULTS: We found that verbal information about a potent pain-relieving effect of the intervention induced a large placebo analgesic response to both acute experimental (F(1,44) = 43.35, p < 0.001) and chronic pain (F(1,44) = 37.72, p < 0.001). However, the placebo responses to experimental and chronic pain were not significantly related (r = 0.012, p = 0.95). An additional conditioning procedure did not significantly enhance placebo analgesia. Treatment history modulated the magnitude of the placebo response: patients with a more negative pain-related treatment history reported significantly larger placebo responses to their own chronic pain (τ = 0.271, p = 0.044). CONCLUSIONS: We could show that placebo responses to both acute and chronic pain are high in pain treatment settings and that treatment history modulates this effect. Different mechanisms might underlie placebo responses to acute and chronic pain. Our findings highlight the necessity of considering placebo responses and treatment history in the treatment of chronic pain. WHAT DOES THIS STUDY ADD?: Placebo analgesia following verbal information of potent pain relief is high in chronic pain patients in a clinical setting. It is modulated by treatment history. Different mechanisms might underlie placebo analgesia to acute and chronic pain.

Effects of fatty acids on activity and calmodulin binding of Ca2+-ATPase of human erythrocyte membranes.

Activation and inhibition of Ca2+-ATPase of calmodulin-depleted human erythrocyte membranes by oleic acid and a variety of other fatty acids have been measured. Low concentrations of oleic acid stimulate the enzyme activity, both in the presence and in the absence of calmodulin. Concomitantly, the affinity of the membrane bound enzyme to calmodulin progressively decreases due to competitive interactions of calmodulin and oleic acid with the enzyme. Removal of oleic acid from the membrane by serum albumin extinguishes the activating effect of oleic acid and restores the ability of the enzyme to bind calmodulin with high affinity. High concentrations of oleic acid induce an almost complete and irreversible loss of enzyme activity which cannot be abolished by removal of oleic acid. Despite a complete loss of enzyme activity, binding of calmodulin to membranes is approximately normal after removal of oleic acid. Activities of (Na+ + K+)-ATPase, Mg2+-ATPase and acetylcholine esterase, as well as the total protein content, show no gross changes upon treatment of membranes with increasing amounts of oleic acid, which seems to exclude that membrane solubilisation by oleic acid causes an inactivation of the enzyme.

Purification and characterization of the Ca2+-ATPase of plasma membranes from Ehrlich ascites mammary carcinoma cells.

Ca2+-ATPase was isolated from plasma membranes of Ehrlich ascites mammary carcinoma cells by means of calmodulin affinity chromatography. The purification procedure included removal of endogenous calmodulin from a Triton X-100 solubilizate of the membranes by DEAE ion-exchange chromatography as an essential step. With respect to its molecular mass, activation by calmodulin, Ca2+-dependent phosphorylation and highly sensitive inhibition by orthovanadate, the purified enzyme resembles the Ca2+-ATPase of erythrocyte membranes. In contrast to the strong calmodulin dependence of the isolated enzyme the Ca2+-ATPase in native Ehrlich ascites carcinoma cell membranes cannot be remarkably stimulated by added calmodulin. It is suggested that the membrane-bound Ca2+-ATPase in the presence of Ca2+ is activated by interaction with endogenously bound calmodulin.

Relation between Ca2+-ATPase and endogenous calmodulin of human erythrocyte membranes.

Short incubation of erythrocyte membranes with oleic acid releases Ca2+-independently bound endogenous calmodulin together with a minor fraction of membrane-associated proteins without destruction of the membranes. The released endogenous calmodulin is similar if not identical to cytosolic calmodulin reversibly bound to ghosts in a Ca2+-dependent manner. The release of endogenous calmodulin proceeds without affecting the activity of Ca2+-ATPase when ghosts are incubated with oleic acid in the presence of Ca2+ plus ATP and thereafter freed from oleic acid by washings with serum albumin. Kinetic parameters of Ca2+-ATPase of ghosts with and without endogenous calmodulin are identical as are amounts of exogenous calmodulin bound to these ghosts. Thus, endogenous calmodulin does not function as an essential part of Ca2+-ATPase.