Distraction From Itch Shows Brainstem Activation Without Reduction in Experimental Itch Sensation.

The central processing of itch is not completely understood. This is the first study to use functional magnetic resonance imaging (fMRI) to examine the central modulation by distraction of experimentally induced itch. A total of 33 healthy volunteers were examined with fMRI. Periods of itch induction without distraction and itch with distraction by a Stroop task (psychological test, where the participants have to decide if the colour of the writing corresponds to the written word, for example if "red" is written in red or not) were counterbalanced during the scanning to examine task-specific changes in blood oxygenation level dependent-signal. The intensity of the subjects' itch sensation, desire to scratch and pain sensation were evaluated. Distraction by a Stroop task did not reduce itch intensity or urge to scratch. However, the Stroop task led to significantly higher activation of the left brainstem when it followed the "pure" itch sensation. Itch and pain seem to have similar inhibition pathways, particularly concerning brainstem activation during distraction. But as itch sensation, in contrast to pain, could not be sufficiently reduced by distraction, both entities might have different modulation systems.

Itch Perception and Skin Reactions as Modulated by Verbal Suggestions: Role of Participant's and Investigator's Sex.

This study investigated sex-specific differences in itch perception and skin reactions, as modulated by verbal suggestions, and the role of the investigator's sex. Healthy volunteers (50 males, 50 females), divided into 4 groups, were tested by male and female investigators. Itch was induced via prick testing with sodium chloride and histamine in 4 runs; 2 control conditions (with no exaggerated verbal comments about expected itch) and 2 experimental conditions (with exaggerated verbal comments). After 5 min, wheal and flare reactions were measured and itch intensity was rated by subjects on a numerical rating scale. Exaggerated verbal suggestions resulted in higher itch intensity ratings in the sodium chloride and histamine condition, and higher unpleasantness ratings and a wheal of greater extent in the sodium chloride condition, as well as a flare of greater extent in the histamine condition. The magnitude of the differences between the exaggerated verbal suggestion conditions and respective control conditions was only significantly different between male and female investigators concerning flare size in the histamine condition. There were no differences between male and female participants. Therefore, sex differences may play only a minor role in nocebo-induced itch perception.

Health-Related Quality of Life in Chronic Pruritus: An Analysis Related to Disease Etiology, Clinical Skin Conditions and Itch Intensity.

BACKGROUND: It is unknown if health-related quality of life (HRQoL) differs between diseases associated with chronic pruritus (CP). OBJECTIVE: To analyze HRQoL in relation to age, gender, skin lesions (primary vs. scratch-induced secondary) and itch intensity. METHODS: Consecutive patients of our itch clinic were assessed with the Dermatology Life Quality Index (DLQI) and visual analogue scale (VAS). RESULTS: In 510 CP patients (282 females; median age, 61.4 years), DLQI scores and VAS values were highly correlated, irrespective of the type of skin lesion. Overall, women had a lower HRQoL compared to men (females: 10.7 ± 6.7, males: 8.9 ± 6.7), but female gender was only associated with worse quality of life in patients <65 years old. CONCLUSION: HRQoL impairment in CP is highly influenced by pruritus intensity but not to the visible skin lesion or underlying cause. With limitations to item bias, DLQI is a suitable instrument for estimating quality of life impairment by CP.

Cutaneous sensory function is not related to depression and anxiety in patients with chronic pruritus with dysesthetic subqualities.

The objective of this study was to examine the subgroup of patients with chronic pruritus with dysesthetic subqualities for the presence of psychiatric comorbidities and to evaluate whether anxiety and depression make a difference in perception of somatosensory stimuli in quantitative sensory testing (QST). Forty-nine patients underwent routine diagnostics, a standardised QST testing battery, a psychosomatic evaluation for psychic comorbidities and filled out 2 questionnaires: the Patient Health Questionnaire for the assessment of depressive mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample had at least one psychiatric comorbid diagnosis. QST parameters were not correlated to anxiety and depression levels. We conclude that psychosomatic evaluation should become part of routine diagnostics of these patients in order to detect and treat psychiatric comorbidity. However, research on somatosensory aspects in these patients seems not to be affected by the levels of anxiety and depression.

Facing the challenges of chronic pruritus: a report from a multi-disciplinary medical itch centre in Germany.

The complex nature and difficult-to-establish aetiology of chronic pruritus (CP) makes it challenging to provide medical care for patients with CP. This challenge can only be met with a multidisciplinary approach. The first multidisciplinary Itch Centre in Germany was established at the University of Münster in 2002 to meet the needs of this patient population. More than 2,500 outpatients and 400 inpatients are diagnosed and receive treatment each year. To ensure evidence-based medical care, an electronic system for medical documentation and patient-reported outcomes was established. Automated data transfer to a research database enables comprehensive data analysis. Our translational research has characterized peripheral and central itch mechanisms, provided novel clustering of CP patients, and identified novel target-specific therapies (e.g. neurokinin 1 receptor-antagonist). The multidisciplinary approach, combined with basic, clinical and translational research, enables comprehensive medical care of patients as well as implementation of high-quality experimental and clinical studies.

Dimensions of the operationalized psychodynamic diagnosis system that predict long-term outcome after inpatient psychotherapy.

BACKGROUND/AIMS: To determine whether the Operationalized Psychodynamic Diagnosis (OPD) system can be useful in predicting patient outcome in the long term. METHODS: OPD was assessed by the therapists prior to and after inpatient treatment. Patients completed psychometric scales at the start and completion of psychosomatic-psychotherapeutic inpatient treatment and at the follow-up. Outcome was defined by the general factor emerging from a principal component analysis of the Brief Symptom Inventory, Hospital Anxiety and Depression Scale and Inventory of Interpersonal Problems at katamnesis, representing individual differences in general distress. RESULTS: Several dimensions of the OPD system proved to be predictors of general distress at the follow-up in 253 former inpatients. Negative predictors of long-term outcome were the high internal impediments to change, namely high secondary gains from illness and also less integrated structural abilities. Positive OPD predictors of long-term outcome were the treatment success achieved at the end of inpatient psychotherapy in changing the illness concept towards a psychological understanding of symptoms, lower levels of complaints and a higher functional level. Also the achieved level of awareness for the individual maladaptive behavioral pattern is predictive of a favorable long-term outcome. CONCLUSIONS: The results provide evidence for the clinical relevance and the predictive value of OPD. © 2014 S. Karger AG, Basel.

[Personal resources in inpatient psychotherapy - Relationships and development]. / Personale Ressourcen in stationärer Fachpsychotherapie - Zusammenhänge und Entwicklung.

OBJECTIVE: We examined how personal resources develop during inpatient psychodynamic psychotherapy, their relationship to symptom development, Operationalized Psychodynamic Diagnosis (OPD-2), and sociodemographic aspects. METHODS: 483 patients were examined using self-assessment questionnaires (Brief Symptom Inventory (BSI), Hospital Anxiety and Depression Scale (HADS), Inventory of Interpersonal Problems (IIP), Questionnaire of Actual Resource Realization (RES)) as well as the expert ratings Global Assessment of Functioning Scale (GAF), Impairment Score (IS), OPD-2, and the Heidelberg Structural Change Scale (HSCS), both at the beginning and the end of treatment. RESULTS: There was a marked improvement in the realization of personal resources during inpatient psychotherapy, which showed significant correlations to the improvement of symptoms. The extent of improvement of resources correlated with the duration of psychotherapy and the assessment of the psychodynamic therapy foci on the HSCS. CONCLUSIONS: The results show that personal resources are activated when successfully working on the psychodynamic foci in psychodynamic inpatient treatment, and that this corresponds to an improvement of symptoms.

Neuropathic itch: diagnosis and management.

Chronic pruritus (CP) is a frequent symptom in the general population; in 8% of all patients, it has a neuropathic origin. CP is of neuropathic origin when nerve fiber damage is responsible for the symptom. The damage can be caused by compression or degeneration of the nerve fibers in the skin or extracutaneous in peripheral nerves or the central nervous system. There are significant differences in the pathogenesis and in the clinical presentation of neuropathic CP. Localized neuropathic CP such as brachioradial pruritus or notalgia paresthetica are due to a circumscribed nerve compression and are often limited on the corresponding dermatome. In contrast, generalized neuropathic CP, as in small fiber neuropathies, may be associated with a systemic or metabolic underlying disease. It is not always easy to establish the diagnosis because a variety of diseases can be responsible for this type of CP. The present study shows an overview of possible diseases, diagnostic tools, and the relevant therapy strategies.

[Age-, gender- and diagnosis-specific changes of body concept during stationary psychosomatic treatment]. / Veränderungen des Körperkonzeptes während stationärer Psychotherapie unter alters-, geschlechts- und diagnose-spezifischen Aspekten.

OBJECTIVE: This study investigates body concept with respect to psychiatric diagnosis, age and gender of inpatients before and after treatment. METHODS/SAMPLE: We examined 153 inpatients with 131 complete datasets. The examination was done at the beginning and at the end of the treatment using the Frankfurt Body Concept Scale (FKKS, Deusinger 1998). The results were calculated by t-test for dependent samples, posthoc Scheffé-tests and univariate variance analysis. RESULTS: The diagnoses indicated a more positive body concept at the end of the treatment (patients with somatoform disorder had effect sizes between -0.2 and -0.4, patients with depressions between -0.4 and -0.7, and patients with eating disorders between -0.3 and -0.7). Gender and age had only little influence on the positive changes. DISCUSSION: The improvement of body concept through inpatient treatment represents a challenge especially for somatoform disorders. The duration of this improvement after inpatient treatment needs further investigation.

[Age-, gender- and diagnosis-specific differences in the body image of psychosomatic outpatients]. / Alters-, geschlechts- und diagnosegruppen-spezifische Unterschiede in den Körperkonzepten bei Patienten einer psychosomatischen Ambulanz.

OBJECTIVE: This study investigates body image with respect to the age, gender, and psychiatric diagnosis (ICD-10) of psychosomatic outpatients based on apriori formulated hypotheses. METHODS/SAMPLE: 865 of the 1114 patients examined over the course of 10 months in a psychosomatic clinic agreed to participate in the study and filled in the Frankfurt Body Concept Scales (FKKS, Deusinger 1998). RESULTS: Patients with one or more psychiatric diagnoses showed significantly more impaired body images than did healthy controls examined with the FKKS. Especially patients with eating disorders stood out. Men generally had more positive body images than women. Higher age was related to some subscales, but not to the sumscore of the FKKS. DISCUSSION: We discuss the complex relationship between gender- and age-related differences, mental disorders and body image, as well as their therapeutic implications.

Psychosomatic and psychiatric disorders and psychologic factors in pruritus.

Chronic pruritus (CP) is a bothersome symptom of many different diseases and is often associated with psychosomatic and psychiatric comorbidity. This review gives an overview of psychologic factors that influence the perception and modulation of pruritus based on the well-known biopsychosocial model. Not only psychic comorbidities, such as anxiety and depression, play an important role in the etiology and perception of pruritus, but also internal factors, including personality, mentalization, suggestibility, and external factors, as well as stress. Expectations concerning the intensity of pruritus can also play a role in itch perception that can be modulated by cognitions and behavior of the patient. Obsessive rituals of scratching and skin manipulation with instruments present challenges in the treatment of CP. Initial studies on the efficacy of psychotherapeutic approaches to different problems, such as scratching, comorbidity, or stress-associated itch, show that these might be very useful additions to the multidisciplinary treatment of pruritus.

Stress-induced allodynia--evidence of increased pain sensitivity in healthy humans and patients with chronic pain after experimentally induced psychosocial stress.

BACKGROUND: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. METHODS: Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test ("Trier Social Stress Test"). RESULTS: Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. CONCLUSIONS: Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.

Sex differences in itch perception and modulation by distraction--an FMRI pilot study in healthy volunteers.

BACKGROUND: Even though itch is a common syndrome of many diseases there is only little knowledge about sex and gender differences in pruritus, especially in central itch perception and modulation. To our knowledge, this is the first fMRI study examining sex differences in perception and its modulation by distraction. METHODS: Experimental itch was induced by application of histamine (0.1 mM) via microdialysis fibers twice at the left forearm and twice at the left lower leg in 33 healthy volunteers (17 females, 16 males). The brain activation patterns were assessed by fMRI during itch without and with distraction (Stroop task). Between the various conditions, subjects were asked to rate itch intensity, desire to scratch and pain intensity. In a second experiment in 10 of the 33 volunteers histamine was replaced by saline solution to serve as control for the 'Stroop' condition. RESULTS: Women generally presented higher itch intensities compared to men during itch over the course of the experiment. A more specific analysis revealed higher itch intensities and desire to scratch in women during experimental induced itch that can be reduced by distraction at the lower legs when itch is followed by 'Stroop'. In contrast, men depicted significant reduction of 'itch' by 'Stroop' at the forearms. Women depicted higher brain activation of structures responsible for integration of sensory, affective information and motor integration/planning during 'itch' and 'Stroop' condition when compared to men. No sex differences were seen in the saline control condition. CONCLUSION: Women and men exhibited localisation dependent differences in their itch perception with women presenting higher itch intensities and desire to scratch. Our findings parallel clinical observations of women reporting higher itch intensities depending on itch localisation and suffering more from itch as compared to men.

IADS, a decomposition product of DIDS activates a cation conductance in Xenopus oocytes and human erythrocytes: new compound for the diagnosis of cystic fibrosis.

DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid) is a commonly used blocker of plasma membrane anion channels and transporters. We observed that DIDS undergoes decomposition while stored in DMSO (dimethyl sulfoxide) forming a biologically active compound. One decomposition product, called IADS, was identified and synthesized. Voltage-clamp and patch clamp experiments on Xenopus laevis oocytes and human erythrocytes revealed that IADS is able to activate a plasma membrane cation conductance in both cell types. Furthermore, we found that IADS induces hemolysis in red blood cells of healthy donors but fails to hemolyze erythrocytes of donors with cystic fibrosis. Thus, IADS stimulated activation of a cation conductance could form the basis for a novel diagnostic test of cystic fibrosis.

Physiological concept for a blood based CFTR test.

We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) could be involved in the volume regulation of human red blood cells (RBC). Experiments were based on two gadolinium (Gd(3+)) sensitive mechanisms, i.e. inhibition of ATP release (thetaATP(i)) and membrane destabilization. RBC of either cystic fibrosis (CF) patients or healthy donors (non-CF) were exposed to KCl buffer containing Gd(3+). A significantly larger quantity of non-CF RBC (2.55 %) hemolyzed as compared to CF RBC (0.89 %). It was found that both of the Gd(3+) mechanisms simultaneously are needed to achieve hemolysis, since either overriding thetaATP(i) by exogenous ATP addition prevented Gd(3+) induced hemolysis, or mimicking thetaATP(i) by apyrase in absence of Gd(3+) could not trigger hemolysis. Additionally, ion driven volume uptake was found to be a prerequisite for Gd3+ induced hemolysis as chloride and potassium channel blockers reduced the Gd(3+) response. The results show that in non-CF RBC Gd(3+) exerts its dual effect leading to hemolysis. On the contrary, in CF RBC, lacking CFTR dependent ATP release, the sole Gd(3+) effect of membrane destabilization is not sufficient to induce hemolysis similar to non-CF. This concept could form the basis of a novel method suitable for testing CFTR function in a blood sample.