The term, takotsubo cardiomyopathy, refers to a relatively recently described form of acute, reversible cardiomyopathy, in which apical akinesia gives the heart the shape of a takotsubo, a Japanese fishing pot for trapping octopus. Takotsubo cardiomyopathy seems to occur mainly in elderly women soon after exposure to severe emotional distress. Symptoms mimic acute myocardial infarction; however, coronary angiography fails to demonstrate coronary occlusion. The condition can trigger sudden cardiac failure or death, yet in survivors cardiac function typically normalizes within a few weeks. Takotsubo cardiomyopathy features remarkably elevated plasma catecholamine levels and depressed cardiac contractile function. Immobilization stress (IMO) of rats can reproduce the ECG and LVG changes that occur in takotsubo cardiomyopathy, both of which are prevented by combined blockade of α- and β-adrenoceptors. Increase of serum estrogen partially attenuates these cardiac changes. Estrogen receptors are expressed in the brain, where estrogen modulates central nervous function and autonomic nervous function. Estrogen attenuated the IMO stress-induced c-Fos expression in the lateral septum, medial amygdaloid nucleus, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, laterodorsal tegmental nucleus and locus coeruleus; these same regions contain central sympathetic neurons and neurons with immunoreactive estrogen receptors. It also down-regulated c-fos mRNA expression in the adrenal gland and the heart, suggesting an increase of estrogen attenuated the stress-induced hypothalamo-sympathoadrenal outflow from the central nervous system to the target organs. Estrogen treatment also up-regulated the levels of cardio-protective substances such as ANP and HSP70 in the heart. These data suggest that reduction of estrogen levels following menopause might be involved in the primary cause of takotsubo cardiomyopathy both by indirect action on the nervous system and by direct action on the heart.

View full abstract

Background: Pain contains sensory discriminative and negative affective components. Although the neural systems responsible for the sensory component of pain have been studied extensively, the neural basis of the affective component is not well understood. We examined the neural circuits and mechanisms underlying the negative affective component of pain using a conditioned place paradigm. Methods: Male Sprague-Dawley rats were used for all experiments under the approval of the Institutional Animal Care and Use Committee. Pain-induced aversion was assessed by a conditioned place aversion (CPA) test. Glutamate and noradrenaline releases within the basolateral amygdaloid nucleus (BLA) and bed nucleus of the stria terminalis (BNST), respectively, were examined by using an in vivo microdialysis technique. Results: Excitotoxic lesions of the BLA abolished intraplantar formalin-induced CPA (F-CPA), but not intraperitoneal acetic acid-induced CPA (A-CPA). On the other hand, excitotoxic lesions of the central amygdaloid nucleus (CeA) abolished both F-CPA and A-CPA. These findings suggest that the BLA and CeA are differently involved in somatic and visceral pain-induced aversion. Next, we examined the role of glutamatergic transmission within the BLA in F-CPA. Microinjection of MK-801 into the bilateral BLA 5min. before intraplantar injection of formalin dose-dependently attenuated F-CPA without affecting nociceptive behaviors. On the contrary, microinjection of neither CNQX nor AP-3 showed any significant effect on F-CPA. In vivo microdialysis experiments revealed that intraplantar injection of formalin induced an increase in the extracellular glutamate level within the BLA. This increase in glutamate was suppressed by morphine perfusion via the microdialysis probe. Moreover, intra-BLA injection of morphine 5min before formalin injection attenuated F-CPA without affecting nociceptive behaviors. Finally, we examined the role of noradrenergic transmission within the BNST, especially the ventral part of the BNST (vBNST), in F-CPA. In vivo microdialysis showed that extracellular noradrenaline levels within the vBNST were significantly increased by intraplantar formalin injection. Using the CPA test, we found that intra-vBNST injection of timolol, a β-adrenoceptor antagonist, dose-dependently attenuated F-CPA without reducing nociceptive behaviors. Intra-vBNST injection of isoproterenol, a β-adrenoceptor agonist, dose-dependently produced CPA even in the absence of noxious stimulation. This isoproterenol-induced CPA was reversed by the co-injection of Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS), a selective PKA inhibitor. Furthermore, intra-vBNST injection of Rp-cAMPS dose-dependently attenuated the F-CPA. Conclusion: These results suggest that glutamatergic transmission via NMDA receptors within the BLA plays a crucial role in the pain-induced aversion, and that in addition to the well-characterized effects on the sensory component of pain, morphine also influences the affective component of pain through an inhibitory effect on intra-BLA glutamatergic transmission. Furthermore, it was demonstrated that PKA activation within the vBNST via the enhancement of β-adrenergic transmission is important for the pain-induced aversion.

View full abstract

Background: Clinical medicine on chronic pain conceives several important problems including invalid managements, disabled quality of life for patients and their families, dysfunctional medical communication, and raised medical socio-economical costs. The International Association for the Study of Pain has proposed the IMMPACT recommendations as an international consensus for clinical pain research in 2003 and 2005. Following this guideline, we overview the multiple assessments for chronic pain in Japan. Methods: We investigated and modified the IMMPACT recommendation for Japanese pain medicine. From the clinical experience for severe chronic pain patients in the Department of Psychosomatic Medicine in Kyushu University Hospital, we specified the several important treatment objects and multiple assessments for the psychosomatic treatment. Results: We introduce the original IMMPACT recommendation and proposed the eleven axes of multiple assessments for Japanese chronic pain patients (pain intensity, pain disability, anxiety・depression・catastrophizing, alexithymia, organic and functional disorder, personality trait・personality disorder・mental retardation, psychiatric disorder, pain behavior, cognition and coping for pain, dysfunctional communication with family or society, medical disbelief) for clarification of psychosomatic treatment objects such as medical disbelief, catastrophizing, pain behavior, alexithymia, pacing disorder and discommunication with significant others. Conclusions: We propose the importance of multiple assessments for clarification of psychosomatic treatment objects. However, the systematic assessments for chronic pain are still on the way to development and need more attention from psychosomatic clinicians and researchers for future development.

View full abstract

Fibromyalgia Syndrome (FMS) is one of the common diseases among the chronic pain disorders characterized by long-lasting generalized pain of the fibro-muscular system and various unidentified complaints. Since the onset and clinical course of FMS involve many psychosocial stress factors and disturbed the endocrine system of womanhood in addition to genetic and physiological factors, it is very important to consider the psychosomatic background of the patient with FMS. Ninety percent of the patients were found to have experienced physical strains such as surgery, accident, trauma, delivery, physical overload and excessive exercise. Remarkable personality traits such as anxiety, fear, anger, obsession, depression and sorrow were observed from clinical interviews and psychological tests. For the physiological background, the amount of urinary metabolites such as VMS, MHPG or 5HIAA showed significantly lower than control healthy subjects, which was very similar to the patients with depression. It is suggested that the dysfunction of serotonin and a noradrenalin-mediated descending pain control system and contraction of muscular and vascular systems followed by circulatory disorders may be involved in chronic pain of FMS. Also the low level of serum acyl-carnitine may explain the psychological and physical exhaustion and accumulated fatigue of FMS. As for medication, ordinary analgesics such as NSAIDs are not effective but antidepressants such as SSRI or SNRI often show a remarkable effect. Anticonvulsants and Kampo herbal medicine have also been reported to be effective for chronic pain of FMS. To the problems of psychological stress and personality, counseling and advanced psychotherapy such as cognitive behavioral therapy (CBT) based on "the personal growth model" may be more important rather than "the medical model". Due to the above condition and situation, psychosomatic specialists will be likely to become main practitioners for the treatment of FMS

View full abstract

In an effort to reflect the content of the symposium presentation at the 49^<th> Japanese Society of Psychosomatic Medicine Annual Meeting, this paper presents the author's clinical experience with patients with chronic pain for 30 years, with three major foci on diagnosis, cognitive behavioral therapy and associated depression

View full abstract

The purpose of the present study was to examine the characteristics of social anxiety in Japanese children using the Social Phobia and Anxiety Inventory for Children (SPAI-C; Beidel et al., 1995). 592 fifth grade students (305 boys, 287 girls) and 467 eighth grade students (230 boys, 236 girls, 1 did not indicate gender) were administered questionnaires on a classwide basis. Of the 26 SPAI-C items, 3 parallel tests consisting of 12-13 items were randomly assigned to the participants. Subsequently, analysis using item response theory was conducted. Results of confirmatory factor analysis supported a 3-factor model consisting of "performance", "social encounters", and "somatic symptoms", with a higher-order factor of "social anxiety". Girls reported stronger social anxiety compared to boys, and eighth graders had higher social anxiety than fifth graders. Furthermore, there was a tendency for the students to dichotomize into two groups, one whose social anxiety increases with social development and the other whose social anxiety returns to normal level. The present results suggested that age, gender, and the characteristics of the social situation influence the magnitude of child and adolescent social anxiety.

View full abstract