Mikihiko Fukunaga

Repeated administration of ghrelin to patients with functional dyspepsia: its effects on food intake and appetite.

BACKGROUND Ghrelin plays a major role in the regulation of food intake (FI), which makes it a strong candidate for the treatment of anorexia. OBJECTIVE We attempted to evaluate the clinical response to repeated ghrelin administration in patients with anorexia caused by functional disorders, such as functional dyspepsia (FD). SUBJECTS AND METHODS Subjects included in this study were those who 1) were diagnosed with functional anorexia, including FD and other eating disorders with the exception of anorexia nervosa; 2) were lean (body mass index (BMI)<22 kg/m(2)); and 3) exhibited decreased FI. Subjects received an i.v. infusion of ghrelin (3 microg/kg) for 30 min twice a day (before breakfast and dinner) for 2 weeks. We investigated the effects of ghrelin administration on FI, appetite, hormones, and metabolic parameters. RESULTS Six patients with FD were enrolled in this study. Ghrelin administration tended to increase daily FI in comparison with levels before and after completion of treatment, but this difference that was the primary endpoint of this study did not reach statistical significance (P=0.084). Hunger sensation was significantly elevated at the end of drip infusion (P<0.0001). No severe adverse effects were observed. CONCLUSIONS These results suggest that ghrelin administration is safe and that this treatment has stimulatory effects on appetite in patients with FD. Further studies are necessary to confirm the efficacy of ghrelin treatment for anorexia-related disorders.

Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients

Objective Ghrelin is a brain-gut peptide that is mainly secreted from gastric endocrine cells (X/A like cells). In addition to promoting growth-hormone release and appetite, ghrelin also affects gastric motility and secretion. Circulating ghrelin levels are related to appetite and energy balance. Functional dyspepsia (FD) is a disorder characterized by the presence of chronic or recurrent symptoms of upper abdominal pain or discomfort. Although no known specific organic abnormalities are present in FD, abnormalities in gastrointestinal motility and sensitivity are thought to play a role in a substantial subgroup of patients. In addition, some patients also suffer from anorexia and body-weight loss. To investigate the role of ghrelin in the pathophysiology of FD, circulating ghrelin levels in affected patients were measured. Material and methods Eighteen Japanese female patients with functional dyspepsia and 18 healthy volunteers were recruited for the study. Acylated and desacyl forms of ghrelin were measured using commercially available enzyme-linked immunosorbent assay kits. Results Although plasma levels of acylated or desacyl ghrelin were not significantly different between healthy subjects and FD patients, plasma acylated, but not desacyl ghrelin, levels were correlated with a subjective symptom score in FD patients. In addition, the ratio of acylated to desacyl ghrelin (A/D ratio) was correlated strongly with acylated, but not desacyl, ghrelin levels. Conclusions The correlation of circulating acylated ghrelin levels with the subjective symptom score and the A/D ratio in FD patients suggest that acylated ghrelin may play a role in the pathophysiology of FD.

High Prevalence of Irritable Bowel Syndrome in Medical Outpatients in Japan

Background and Goals The prevalence of irritable bowel syndrome (IBS) among Japanese patients who visit hospitals departments of internal medicine is thought to be high. However, no clear statistical evidence has been provided to support such a claim. We tested the hypotheses that the prevalence of IBS in medical outpatients clinics in Japan is high, and that IBS patients feel more psychosocial stress than patients without IBS. Study The subjects in this study were 633 patients who visited participating physicians. Patients were asked to fill in the Japanese version of the Rome II Modular Questionnaire (RIIMQ) for IBS diagnosis, the Self-reported Irritable Bowel Syndrome Questionnaire (SIBSQ) for severity of the disease and the demographic questionnaire for perceived stress and life style. Results Rome II-defined IBS was diagnosed in 196 patients (31%). Analysis of variance revealed significant difference in the IBS scores of SIBSQ among IBS subjects (39.0±11.1, mean±SD), functional bowel disorder subjects (27.1±10.2), and normal subjects (24.0±10.0, P<0.01). The prevalence of IBS depending on age formed 2 peaks, one among adolescents and the other among the elderly. IBS patients had significantly more perceived stress (P<0.0001), irregular sleep habit (P<0.0001), and irregular meal habit (P<0.0001) than those without IBS. Conclusions The prevalence of IBS among medical outpatients in Japan is high (31%). IBS subjects among medically ill patients are thought to have more perceived stress and less regular life styles.

Depression and Anxiety Correlate Differently with Salivary Free Cortisol in the Morning in Patients with Functional Somatic Syndrome

Patients presenting with functional somatic syndrome (FSS) are common, and the symptoms are persistent and difficult to treat for doctors and costly for society. The aim of this study was to clarify the common pathophysiology of FSS, especially the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and psychological characteristics of patients with FSS. The subjects were 45 patients with FSS and 29 healthy controls. Salivary free cortisol was measured in the morning, and psychological tests examining depression, anxiety and quality of life (QOL) were performed on the same day. In patients with FSS, depressive scores showed a significant negative correlation with salivary free cortisol in the morning, although in healthy controls, cortisol showed a significant positive correlation with depressive scores. In addition, the correlation between other psychological test scores and cortisol secretion in patients with FSS contrasted with that of controls. The relationship between cortisol and depression, anxiety or QOL, suggests that the HPA axis of patients with FSS is dysfunctional and does not function properly when patients with FSS are under stress. This dysfunction may explain the pathology of medically unexplained persistent symptoms of patients with FSS.

Links among emotional awareness, somatic awareness and autonomic homeostatic processing

Emotional awareness and somatic interoceptive awareness are essential processes for human psychosomatic health. A typical trait of lacking emotional awareness related to psychosomatic symptoms is alexithymia. In contrast, alexisomia refers to the trait of lacking somatic awareness. Links between emotional and somatic awareness and homeostatic processing are also significant for the psychosomatic health. The purpose of the present paper is to review the links among emotional awareness, somatic interoceptive awareness and autonomic homeostatic processing. On the basis of the collected evidence, the following arguments were presented1: (1) The main subcortical neural substrates for these processes are limbic-related systems, which are also responsible for autonomic functions for optimization of homeostatic efficiency. (2) Considerable studies have shown that autonomic activity and/or reactivity to stress correlate with both emotional and interoceptive awareness. A hypothesis was advocated about the links between the two types of awareness and autonomic function: Autonomic dysfunction, especially high sympathetic tone at baseline and/or attenuated reactivity or variability to stress, appears to be involved in disturbance of emotional and interoceptive awareness. (3) Several studies suggest that a link or a cooperative relationship exists between emotional and somatic awareness, and that somatic awareness is the more fundamental of the two types of awareness. Emotional awareness, somatic awareness and autonomic homeostatic processing generally occur in parallel or concurrently. However, some complex features of pathologies include coexistence of reduced interoceptive awareness and somatosensory amplification. The autonomic homeostatic process is fundamentally involved in emotional and somatic awareness. Investigation of these types of awareness with both neuroimaging evaluations and estimation of peripheral autonomic function are required as next steps for exploration of the relationship between awareness and human somatic states including somatic symptoms as well as general psychosomatic health.

Psychological characteristics of Japanese patients with chronic pain assessed by the Rorschach test

BackgroundThe increasing number of patients with chronic pain in Japan has become a major issue in terms of the patients quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients.MethodsThe Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test.ResultsPatients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain.ConclusionsData gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are likely to be highly beneficial, and we thus recommend their incorporation into the course of current pain treatments.

An exploratory study of subgrouping of patients with functional somatic syndrome based on the psychophysiological stress response: its relationship with moods and subjective variables.

Objective: To study the characteristics and subjective estimations of subgroups of patients with functional somatic syndrome (FSS). A characteristic in patients with FSS was reportedly hyporeactivity in the psychophysiological stress response (PSR). Methods: The PSR was measured in 59 FSS patients and 41 healthy controls. Autonomic lability scores (ALSs) of six psychophysiological measurements on PSR were calculated. Cluster analysis using the ALSs was performed in the FSS group. A discriminant analysis was also performed to identify the criterion of the subgrouping. Factor analysis scores of the six ALSs, and moods and subjective variables were compared between the subgroups. Results: Cluster analysis divided the FSS patients into two clusters. Three groups (low-lability, high-lability, and control groups) were compared. All factor scores of autonomic lability significantly differed between the low- and high-lability groups, and between the low-lability and control groups. The mood scores were higher in the high-lability group than in the low-lability group. The duration of suffering was significantly longer in the high-lability group than in the low-lability group. The distributions of symptoms and diagnosis did not significantly differ between the subgroups. Conclusions: We have tentatively verified that there are two subgroups based on the autonomic lability among FSS patients, which were independent of the type of symptoms and diagnostic category. Autonomic lability is an important axis in the multiaxial diagnosis of FSS. FSS = functional somatic syndrome; IBS = irritable bowel syndrome; FMS = fibromyalgia syndrome; FGID = functional gastrointestinal disorder; ALS = autonomic lability score; PSR = psychophysiological stress response; ANS = autonomic nervous system; VAS = visual analogue scale; SEMG = surface-electromyography; TEMP = skin temperature; SCL = skin conductance level; NSSCR = nonspecific skin conductance response; BVPAmp = blood volume pulse amplitude; STS = subjective tension score.

Saliva amylase as a measure of sympathetic change elicited by autogenic training in patients with functional somatic syndromes.

The aim of this study was to discuss the effect of autogenic training (AT) on patients with functional somatic syndrome (FSS) using salivary amylase, the skin temperature of the finger, subjective severity of symptoms, and psychological characteristics as measures. We assessed 20 patients with FSS and 23 healthy controls before and after AT. Baseline levels of salivary amylase prior to an AT session were significantly higher in the FSS group than in the control group. However, this difference was not significant after AT. The skin temperature of the finger increased after AT in both the FSS and control groups. AT contributed to the improvement of somatic symptoms in patients with FSS. Our results regarding psychological characteristics suggest that mood disturbances are deeply involved in the pathology of FSS. Individuals with FSS exhibited elevated levels of sympathetic activity compared with healthy controls. Our data indicates that AT eased dysregulation of the autonomic nervous system in patients with FSS. Thus, salivary amylase may be a useful index of change induced by AT in patients with FSS.

Pain threshold reflects psychological traits in patients with chronic pain: a cross-sectional study

BackgroundChronic pain enhances sensory sensitivity and induces the biased development of psychological traits such as depression and pain catastrophizing, leading to the formation of heterogeneous conditions. Fluctuations in the sensory-related thresholds of non-injured sites (with normal peripheral tissue) in patients with chronic pain are thought to be related to central sensitization. The objectives of this study were to analyze the association between pain tolerance thresholds (PTTs) in non-injured sites and the psychological traits of patients with chronic pain and to evaluate the usefulness of PTT measures in assessments of pathological conditions related to chronic pain.MethodsThis study included 57 patients with chronic pain. The PTTs were measured in non-injured sites with quantitative sensory testing (QST) with electrical stimulation and then classified with cluster analysis. The Short-Form McGill Pain Questionnaire was used to subjectively assess pain in the injured sites. The Minnesota Multiphasic Personality Inventory (MMPI) was used to assess the patients’ psychological traits.ResultsBased on the cluster analysis of PTTs, the patients were classified into a High-Sensitivity group and an Others group consisting of the remaining patients. The results of the MMPI profiles showed that the High-Sensitivity group included significantly more patients with the Neurotic Triad pattern and no patients with the Conversion V pattern. The scores of the hypochondriasis and hysteria scales were significantly lower in the High-Sensitivity group than in the Others group.ConclusionsThis study indicated that patients with chronic pain can be classified according to PTTs in non-injured sites and suggests that patients with High-Sensitivity have characteristic psychological traits. Assessment of PTTs in non-injured sites would be useful for evaluating the psychological condition of patients with chronic pain.

Myofacial trigger points in advanced cancer patients

Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation.We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points.