Acupuncture combined with western medicine for the treatment of hypertension: A protocol for an updated systematic review and meta-analysis.

BACKGROUND: Hypertension is a kind of cardiovascular syndrome with the main clinical manifestation of continuous increase of systemic arterial blood pressure. Hypertension coexists with other cardiovascular risk factors and is an important risk factor for cardiovascular and cerebrovascular diseases. Acupuncture is an important part of Traditional Chinese Medicine intervention. The antihypertensive effect of acupuncture on hypertension is based on the neuroendocrine system, characterized by multichannel and multitarget. This study aims to provide latest and updated proof of systematic review to assess the effectiveness and safety of acupuncture for hypertension. METHODS: We will systematically search 9 databases from their inceptions to February 2021. Only randomized controlled trials of acupuncture combined with western medicine in the treatment of hypertension will meet the inclusion criteria. The main outcome measures we focus on include clinical efficacy, syndrome efficacy, Traditional Chinese Medicine syndrome score, diastolic and systolic blood pressure changes, blood pressure variability, heart rate variability, pulse rate variability, and adverse reactions. The research screening, data extraction, and risk of bias assessment will be employed by 2 reviewers independently, and disagreement will be decided by a third senior reviewer. The Revman 5.3 software will be used for meta-analysis. The confidence of proof will be rated adopting grading of recommendations assessment, development and evaluation tool and methodological quality of this research will be assessed using assessment of multiple systematic reviews-2 and risk of bias in systematic reviews. The publication quality will be evaluated by preferred reporting items for systematic reviews and meta-analyses (PRISMA). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for hypertension therapy by acupuncture combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of acupuncture for hypertension. REGISTRATION NUMBER: INPLASY 202150047.

Neuroendocrine changes in the hypothalamic-neurohypophysial system in the Wistar audiogenic rat (WAR) strain submitted to audiogenic kindling.

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.

Neuroendocrine disruption is associated to infertility in chronically stressed female rats.

Infertility is a growing worldwide public health problem, and stress is a main factor exerting detrimental effects on female reproduction. However, knowledge regarding the neuroendocrine changes caused by chronic stress in females is limited. Therefore, this study assessed the effects of stress on hormones that control female reproduction during the proestrus and diestrus stages of the estrous cycle, as well as its effects on fertility. Adult females were assigned to either a control or a stress group. Stress consisted of exposure, for 15 min, to cold-water immersion daily for 30 days. Estrous cyclicity, female sexual behavior, as well as hypothalamic kisspeptin, gonadotropin releasing hormone (GnRH) content, serum luteinizing hormone (LH), estradiol (E2), progesterone (P4), corticosterone (CORT) and fertility were assessed after chronic stress. The results show that chronically stressed females exhibited disrupted estrous cyclicity, decreased receptivity, low pregnancy rates and lower numbers of fetuses. The content of Kisspeptin and GnRH in the Anteroventral Periventricular/medial Preoptic Area decreased during proestrus, while Kisspeptin increased in the Arcuate nucleus in proestrus and diestrus. Serum LH decreased only during proestrus, whereas E2 and P4 concentrations decreased during proestrus and diestrus, with a concomitant increase in CORT levels in both stages. As a whole, these results indicate that chronic stress decreases Kisspeptin content in AVPV nucleus and GnRH in POA in females, and might induce disruption of the LH surge, consequently disrupting estrous cyclicity and fertility, leading to lower rates of pregnancy and number of fetuses.

Lack of AR in LepRb Cells Disrupts Ambulatory Activity and Neuroendocrine Axes in a Sex-Specific Manner in Mice.

Disorders of androgen imbalance, such as hyperandrogenism in females or hypoandrogenism in males, increase risk of visceral adiposity, type 2 diabetes, and infertility. Androgens act upon androgen receptors (AR) which are expressed in many tissues. In the brain, AR are abundant in hypothalamic nuclei involved in regulation of reproduction and energy homeostasis, yet the role of androgens acting via AR in specific neuronal populations has not been fully elucidated. Leptin receptor (LepRb)-expressing neurons coexpress AR predominantly in hypothalamic arcuate and ventral premammillary nuclei (ARH and PMv, respectively), with low colocalization in other LepRb neuronal populations, and very low colocalization in the pituitary gland and gonads. Deletion of AR from LepRb-expressing cells (LepRbΔAR) has no effect on body weight, energy expenditure, and glucose homeostasis in male and female mice. However, LepRbΔAR female mice show increased body length later in life, whereas male LepRbΔAR mice show an increase in spontaneous ambulatory activity. LepRbΔAR mice display typical pubertal timing, estrous cycles, and fertility, but increased testosterone levels in males. Removal of sex steroid negative feedback action induced an exaggerated rise in luteinizing hormone in LepRbΔAR males and follicle-stimulating hormone in LepRbΔAR females. Our findings show that AR can directly affect a subset of ARH and PMv neurons in a sex-specific manner and demonstrate specific androgenic actions in the neuroendocrine hypothalamus.

Gaining resilience and reducing stress in the age of COVID-19.

PURPOSE OF REVIEW: The world is experiencing the evolving situation associated with the outbreak of the Corona Virus Disease-2019 (COVID-19) virus, and there is more of need than ever for stress management and self-care. In this article, we will define the physiological, psychological and social aspects, stages, and components of stress reactions in the context of COVID-19, review the relevant literature on stress reactions, and offer some guidance on how to help patients mitigate the physiological and psychological impact of the pandemic through resilience-building techniques. RECENT FINDINGS: There is continued evidence that the fight or flight response involves activation throughout the body at physiological, biochemical and immune levels. This response can be mitigated through increasing parasympathetic nervous system activation as well as cognitive and behavioral interventions. SUMMARY: This article will review the stress, provide a theoretical layout to predict upcoming response, and offer clinicians some practical interventions to employ as the stress of the COVID-19 pandemic continues.

Active fraction combination from Liuwei Dihuang decoction (LW-AFC) ameliorates corticosterone-induced long-term potentiation (LTP) impairment in mice in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LW), a classic formula in Traditional Chinese medicine (TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6 herbs including Dihuang (prepared root of Rehmannia glutinosa (Gaertn.) DC.), Shanyao (rhizome of Dioscorea polystachya Turcz.), Shanzhuyu (fruit of Cornus officinalis Siebold & Zucc.), Mudanpi (root bark of Paeonia × suffruticosa Andrews), Zexie (rhizome of Alisma plantago-aquatica L.) and Fuling (scleorotia of Wolfiporia extensa (Peck) Ginns). LW-active fraction combination (LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. Recent researches indicate that the "kidney deficiency" is related to a disturbance in the neuroendocrine immunomodulation (NIM) network, and glucocorticoids play an important role in kidney deficiency. AIM OF THE STUDY: This study evaluated the effects of LW-AFC and the active fractions (polysaccharide, LWB-B; glycoside, LWD-b; oligosaccharide, CA-30) on corticosterone (Cort)-induced long-term potentiation (LTP) impairment in vivo. MATERIALS AND METHODS: In this study, LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration (i.g., i.p., 7 days) or single administration (i.c.v., i.g., i.p.). Cort was injected subcutaneously 1 h before the high-frequency stimulation (HFS) to induce LTP impairment. Moreover, in order to research on the possible effective pathways, an antibiotic cocktail and an immunosuppressant were also used. RESULTS: Chronic administration (i.g.) of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Single administration (i.c.v., i.g., i.p.) of any of the active fractions had no effect on Cort-induced LTP impairment, while chronic administration (i.g., i.p.) of LWB-B or LWD-b showed positive effects against Cort. Interestingly, CA-30 only showed protective effects via i.g. administration, and there was little effect when CA-30 was administered i.p. In addition, when the intestinal microbiota was disrupted by application of the antibiotic cocktail, CA-30 showed little protective effects against Cort. The effects of LW-AFC were also abolished when the immune function was inhibited. In the hippocampal tissue, Cort treatment increased corticosterone and glutamate, and LW-AFC could inhibit the Cort-induced elevation of corticosterone and glutamate; there was little change in D-serine in Cort-treated animals, but LW-AFC could increase the D-serine levels. CONCLUSION: LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Their protective effects are unlikely by a direct way, and immune modulation might be the common pathway. CA-30 could protect LTP from impairment via modulating the intestinal microbiota. Decreasing corticosterone and glutamate and increasing D-serine in the Cort-treated animals' hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC. Further study is needed to understand the underlying mechanisms.

Physiological and pathophysiological roles of hypothalamic astrocytes in metabolism.

The role of glial cells, including astrocytes, in metabolic control has received increasing attention in recent years. Although the original interest in these macroglial cells was a result of astrogliosis being observed in the hypothalamus of diet-induced obese subjects, studies have also focused on how they participate in the physiological control of appetite and energy expenditure. Astrocytes express receptors for numerous hormones, growth factors and neuropeptides. Some functions of astrocytes include transport of nutrients and hormones from the circulation to the brain, storage of glycogen, participation in glucose sensing, synaptic plasticity, uptake and metabolism of neurotransmitters, release of substances to modify neurotransmission, and cytokine production, amongst others. In the hypothalamus, these physiological glial functions impact on neuronal circuits that control systemic metabolism to modify their outputs. The initial response of astrocytes to poor dietary habits and obesity involves activation of neuroprotective mechanisms but, with chronic exposure to these situations, hypothalamic astrocytes participate in the development of some of the damaging secondary effects. The present review discusses not only some of the physiological functions of hypothalamic astrocytes in metabolism, but also their role in the secondary complications of obesity, such as insulin resistance and cardiovascular affectations.

How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases.

The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10. However, because of excessive cost and complexity of analyzing the data regarding the secretion of the single cytokines, the relation between lymphocyte-induced immune activation and monocyte-macrophage-mediated immunosuppression has been recently proven to be expressed by the simple lymphocyte-to-monocyte ratio (LMR). The evidence of low LMR values has appeared to correlate with a poor prognosis in cancer and with a disease control in the autoimmune diseases. Moreover, since the in vivo immunoinflammatory response is physiologically under a neuroendocrine modulation, for the evaluation of patient biological response it would be necessary to investigate the function of at least the two main neuroendocrine structures involved in the neuroendocrine modulation of the immune responses, consisting of the hypothalamic-pituitary-adrenal axis and the pineal gland, since the lack of physiological circadian rhythm of cortisol and pineal hormone melatonin has appeared to be associated with a worse prognosis in the human systemic diseases.

Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats.

Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals. Furthermore, Western blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+-2Cl- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats. Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and glucose levels in STZ rats. Last, investigation that used rats expressing an AVP-enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP neurons was much more intense in STZ rats than in control rats. We conclude that altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are important changes in AVP neurons that would increase AVP secretion in DM. Our data suggest that Cl- transporters in AVP neurons are potential targets of antidiabetes treatments.

Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept.

Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness.

STRESS IN PEDIATRIC PATIENTS--THE EFFECT OF PROLONGED HOSPITALIZATION.

Long-term hospitalization emotionally impacts any patient, especially children, and is defined as a long period of time during which the patient is hospitalized and experiences isolation from his or her family, friends and home. Stressful situations trigger a nonspecific response that involves multiple physiological mechanisms. Currently, because of the complexity of these mechanisms, there are no laboratory markers that allow the quantification of the stress intensity felt by the patient. Laboratory determinations currently used in evaluating the response to stress are neuroendocrine, immunological and metabolic. The neuroendocrine system is the first to respond to stressful events. Stress stimulates the hypothalamus, leading to the release of CRH, which stimulates the pituitary gland to produce ACTH. Chronic stress directs the synthesis towards cortisol, which may lead to hypo secretion of the other adrenal steroid hormones. The hospital and the disease are stressors for children and caregivers, since stress can interfere with the normal development of young patients, affecting them in the long term. Admitting a child to hospital means interrupting his or her normal daily life and changing the environment that is familiar to him or her. Therefore, the involvement of the family doctor is very important, as many conditions can be solved by visiting his or her office and thus eliminating the need for hospitalization in a pediatric hospital. If, however, the nature of the condition requires that the child should be seen by a pediatrician, the period of hospitalization should not be much extended so as to prevent the appearance of other possible problems that might influence the child's state.

Maternal Vitamin D Deficiency Programs Reproductive Dysfunction in Female Mice Offspring Through Adverse Effects on the Neuroendocrine Axis.

Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.

Amplified pain syndromes in children: treatment and new insights into disease pathogenesis.

PURPOSE OF REVIEW: Although many diagnostic terms are used for pediatric chronic pain, evidence suggests a common thread of signal amplification, leading to the unifying term 'amplified pain syndromes'. Ongoing research provides new insights into biopsychosocial contributors and treatments for pediatric amplified pain syndromes. RECENT FINDINGS: Basic science indicates a complex interplay of genetic, epigenetic, neurochemical, endocrine, and inflammatory contributors, along with environmental and psychological factors. Although medications and interventions remain common approaches to children with chronic pain, their evidence is limited. Preliminary evidence exists for mindfulness-based therapies, yoga, and other complementary/alternative medicine approaches. The strongest evidence is for exercise-based and cognitive-behavioral treatments, in particular, when combined in a multidisciplinary format. Intensive approaches (pain rehabilitation) have the potential to effectively and efficiently treat those most disabled by amplified pain syndromes, and lead to sustained improvement in pain, functioning, and medical utilization. SUMMARY: Although understanding of the mechanisms underlying pediatric amplified pain syndromes evolves, standard of care is multidisciplinary emphasizing exercise therapy, cognitive-behavioral treatment, and self-regulation. Treatment should target full return to physical function, which leads to subsequent improvement or resolution of pain. Multidisciplinary care can be coordinated by a rheumatologist or other physician with appropriate referrals, or through a multidisciplinary team.

PTSD symptom reduction with mindfulness-based stretching and deep breathing exercise: randomized controlled clinical trial of efficacy.

CONTEXT: Abnormal cortisol levels are a key pathophysiological indicator of post-traumatic stress disorder (PTSD). Endogenous normalization of cortisol concentration through exercise may be associated with PTSD symptom reduction. OBJECTIVE: The aim of the study was to determine whether mindfulness-based stretching and deep breathing exercise (MBX) normalizes cortisol levels and reduces PTSD symptom severity among individuals with subclinical features of PTSD. DESIGN AND SETTING: A randomized controlled trial was conducted at the University of New Mexico Health Sciences Center. PARTICIPANTS: Twenty-nine nurses (28 female) aged 45-66 years participated in the study. INTERVENTION: Sixty-minute MBX sessions were conducted semiweekly for 8 weeks. MAIN OUTCOME MEASURES: Serum cortisol was measured, and the PTSD Checklist-Civilian version (PCL-C) was performed at baseline and weeks 4, 8, and 16. RESULTS: Twenty-nine participants completed the study procedures, 22 (79%) with PTSD symptoms (MBX, n = 11; control, n = 11), and 7 (21%) without PTSD (BASE group). Eight-week outcomes for the MBX group were superior to those for the control group (mean difference for PCL-C scores, -13.6; 95% confidence interval [CI], -25.6, -1.6; P = .01; mean difference for serum cortisol, 5.8; 95% CI, 0.83, 10.8; P = .01). No significant differences were identified between groups in any other items. The changes in the MBX group were maintained at the 16-week follow-up (P = .85 for PCL-C; P = .21 for cortisol). Our data show that improved PTSD scores were associated with normalization of cortisol levels (P < .05). CONCLUSIONS: The results suggest that MBX appears to reduce the prevalence of PTSD-like symptoms in individuals exhibiting subclinical features of PTSD.

A reinterpretation of the pathogenesis and cure of cancer according to the psychoneuroimmunological discoveries.

The recent discoveries in the oncological researches have demonstrated that the prognosis of the neoplastic diseases depends on not only the biological characteristics of tumors, including oncogene expression and growth factor receptor activity, but also on the immune status of cancer patients. This is because the well-documented importance of the anticancer immunity in the initiation of the tumor that is mainly modulated by lymphocytes. In addition, the knowledge on the interactions between the immune and neuroendocrine systems has demonstrated that the immune responses are physiologically under a psychoneuroendocrine control. In particular, it has been confirmed that the activation of the brain opioid tone may suppress the generation of an effective anticancer immunity, whereas it is stimulated by other neuroendocrine structure, namely the pineal gland, through the release of at least two indole hormones with anticancer activity, melatonin and 5-methoxytryptamine, exerting both antiproliferative and immunostimulatory effects. By investigating the immune and neuroendocrine functions in cancer patients, it has been observed that cancer progression is associated with a progressive decline in the pineal function, which would constitute the main cancer-related endocrine deficiency, and the occurrence of the irreversible immune alterations. The most prognostically important factors would consist of a diminished endogenous production of anticancer cytokines, such as IL-2 and IL-12, as well as an abnormally enhanced secretion of cytokines provided by suppressive effect on the anticancer immunity, namely IL-14, TGF-beta, and IL-6. The psychoneuroimmunotherapeutic approach in the treatment of cancer would simply consist of the corrections of the various endocrine and immune cancer-related alterations in an attempt to re-establish the neuroimmune condition of the health status.

Cluster headache and the hypothalamus: causal relationship or epiphenomenon?

Typical clinical features of cluster headache (CH) include circadian/circannual rhythmicity and ipisilateral cranial autonomic features. This presentation has led to the assumption that the hypothalamus plays a pivotal role in this primary headache disorder. Several studies using neuroimaging techniques or measuring hormone levels supported the hypothesis of a hypothalamic involvement in the underlying pathophysiology of CH. Animal studies added further evidence to this hypothesis. Based on previous data, even invasive treatment methods, such as hypothalamic deep brain stimulation, are used for therapy. However, the principal question of whether these alterations are pathognomonic for CH or whether they might be detected in trigeminal pain disorders in general, in terms of an epiphenomenon, is still unsolved. This article summarizes studies on hypothalamic involvement in CH pathophysiology, demonstrates the involvement of the hypothalamus in other diseases and tries to illuminate the role of the hypothalamus based on this synopsis.

A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities.

Posttraumatic stress disorder (PTSD) is a serious and debilitating condition with a prevalence rate of approximately 8% in the United States. Given the number of veterans returning from conflicts around the globe with PTSD, and the substantial number of civilians experiencing traumas, new perspectives on the biology of PTSD are needed. Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system function in patients with PTSD. Given that both glucocorticoids and catecholamines exert powerful effects on the immune system, it is surprising that relatively few studies have examined immune changes in patients with PTSD. Moreover, patients with PTSD are known to have increased rates of comorbidity with somatic disorders that involve immune and inflammatory processes. Patients with PTSD have been found to exhibit a number of immune changes including increased circulating inflammatory markers, increased reactivity to antigen skin tests, lower natural killer cell activity, and lower total T lymphocyte counts. Studies with humans and rodents suggest that certain proinflammatory cytokines are able to induce neurochemical and behavioral changes that resemble some key features of PTSD. This short article reviews immune alterations in PTSD, and considers possible mechanisms by which such changes may be related to neuroendocrine alterations and medical comorbidities of PTSD.

The use of the zebrafish model in stress research.

The study of the causes and mechanisms underlying psychiatric disorders requires the use of non-human models for the test of scientific hypotheses as well as for use in pre-clinical drug screening and discovery. This review argues in favor of the use of zebrafish as a novel animal model to study the impact of early (stressful) experiences on the development of differential stress phenotypes in later life. This phenomenon is evolutionary conserved among several vertebrate species and has relevance to the etiology of psychiatric disorders. Why do we need novel animal models? Although significant progress has been achieved with the use of traditional mammalian models, there are major pitfalls associated with their use that impedes progress on two major fronts: 1) uncovering of the molecular mechanisms underlying aspects of compromised (stress-exposed) brain development relevant to the etiology of psychiatric disorders, and 2) ability to develop high-throughput technology for drug discovery in the field of psychiatry. The zebrafish model helps resolve these issues. Here we present a conceptual framework for the use of zebrafish in stress research and psychiatry by addressing three specific domains of application: 1) stress research, 2) human disease mechanisms, and 3) drug discovery. We also present novel methodologies associated with the development of the zebrafish stress model and discuss how such methodologies can contribute to remove the main bottleneck in the field of drug discovery.

Impact of stress on cancer metastasis.

The influence of psychosocial factors on the development and progression of cancer has been a longstanding hypothesis since ancient times. In fact, epidemiological and clinical studies over the past 30 years have provided strong evidence for links between chronic stress, depression and social isolation and cancer progression. By contrast, there is only limited evidence for the role of these behavioral factors in cancer initiation. Recent cellular and molecular studies have identified specific signaling pathways that impact cancer growth and metastasis. This article provides an overview of the relationship between psychosocial factors, specifically chronic stress, and cancer progression.