A unifying theory linking the prolonged efficacy of the stellate ganglion block for the treatment of chronic regional pain syndrome (CRPS), hot flashes, and posttraumatic stress disorder (PTSD)

The mechanism of action of the stellate ganglion block (SGB) is still uncertain; however it has been used successfully in treatment of chronic regional pain syndrome (CRPS) for many years. Our new insights in to the mechanism of action of the stellate ganglion block were first reported in 2007 in our publication detailing the control of hot flashes with the use of stellate ganglion blockade. We have demonstrated very significant results in the treatment of hot flashes and our most recent application of this block has been for the treatment of posttraumatic stress disorder (PTSD).Stellate ganglion has been demonstrated to have second and third order neurons connections with the central nervous system nuclei that modulate body temperature, neuropathic pain, the manifestations of PTSD, and many other areas.We believe that the commonality between the CRPS, HF and PTSD is the trigger of increased nerve growth factor (NGF) leading to the increase in brain norepinephrine (NR), which in turn is affected by the SGB leading to a prolonged reduction of NGF and eventually a decrease in NR. This, in turn, leads to a reduction or elimination of many of the symptoms of CRPS, Hot flashes, and PTSD.     

Novel mechanism of action hypothesized for stellate ganglion block related to melatonin

The mechanism of action of stellate ganglion block has generally been explained by vasodilation within its sphere of innervation. However, the success of treatment cannot always be explained by just one mechanism of action, because its clinical indications in Japan extend to many diseases, including systemic diseases. We propose a new mechanism of action for stellate ganglion block that is based on correction of melatonin rhythm disorder resulting from increased sympathetic nerve tone and does not involve vasodilation.     

低雌激素引发潮热的外周机制

近年来,潮热已成为困扰因各种原因导致低雌激素状态的妇女工作和生活的主要因素之一,严重影响其生活质量。目前国际公认潮热的发生是中枢体温调节热中性带变窄,体温调节系统紊乱所致。既往主要是研究雌激素降低后,引起体温调节中枢功能异常,从而诱发潮热的机制,而较少关注其中枢整合后传出通路的外周体温调节作用方式的变化情况。我们从外周体温调节的3种基本方式,即交感神经系统调节、躯体神经系统调节和肾上腺激素与甲状腺激素分泌调节,对低雌激素状态下的潮热的外周体温调节机制进行综述。     

Stellate ganglion block for treating hot flashes: A viable treatment option or sham procedure?

Stellate ganglion block (SGB) has been used for over 70 years to treat various cervical pain syndromes. Over the past 8 years, 4 different groups have reported on SGB's effects on hot flashes from unblinded, open-label trials. Review of these studies has shown markedly disparate results in terms of the magnitude of hot flash reduction from Baseline with one trial showing a 90% reduction in hot flashes and 3 other trials showing 28–44% reductions in hot flashes. The inconsistencies in these results in addition to the known potentially large (>50%) placebo effects that can occur in randomized controlled hot flash clinical trials make it difficult to render any conclusions regarding the efficacy of SGB for hot flashes at this time. A randomized controlled trial, including a sham saline treatment arm, needs to be performed to properly assess SGB's effects on hot flashes, Methodological challenges with such a study design are addressed and several suggestions are proposed to manage these challenges.     

The pathomorphology of the intra- and extraorganic neural apparatus of the heart in congenital defects

Different components of the heart sympathetic and parasympathetic innervation were studied in 22 autopsy cases of congenital heart defects. Central efferent neurons in the lateral horns of the upper thoracic segments of the spinal cord and in the dorsal nucleus of the medulla oblongata are damaged stronger than the neurons of the upper neck and stellate sympathetic nodes and the heart intramural ganglia this resulting in the selective destruction of the preganglionic nervous conducting elements. It is suggested that the disturbance of the connection between the heart nervous structures and the central nervous system exerts a negative influence on its function.     

Origin of sympathetic and sensory innervation of the temporo-mandibular joint. A retrograde axonal tracing study in the rat.

The cells of origin of sensory and sympathetic innervation of the temporo-mandibular joint were studied by the intraaxonal transport method. Horseradish peroxidase or lectin-conjugated horseradish peroxidase was injected into the temporo-mandibular joint unilaterally in adult rats. Labelled cells were observed ipsilaterally in the superior cervical and stellate sympathetic ganglia, in the sensory trigeminal ganglion and in the second to fifth dorsal root ganglia; none were found contralaterally. The results are discussed in relation to the hypothesis that a nervous mechanism might be involved in the pathogenesis of joint inflammation.     

Physiology of hot flashes

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non‐Western areas. The symptoms are characteristic of a heat‐dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4°C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known. Am. J. Hum. Biol. 13:453–464, 2001. © 2001 Wiley‐Liss, Inc.     

Stellate ganglion block may prevent the development of neurogenic pulmonary edema and improve the outcome

Neurogenic pulmonary edema (NPE) is an acute and serious complication after a central nervous system insult with high mortality. The pronounced activation of sympathetic nervous system and the release of vasoactive substances are necessary prerequisites for the development of NPE. We introduce a hypothesis that stellate ganglion block (SGB) may prevent NPE development on the basis of the inhibition of sympathetic overactivation, reduction of the concentration of norepinephrine and attenuation of baroreflex sensitivity, and improve the outcome by improving cerebral blood flow and pulmonary circulation and maintaining cardiovascular stability. In clinical practice, the guidance technique and close monitoring might guarantee the safety of SGB. If our hypothesis is supported by further experiments, this may open a new doorway for the treatment of NPE.     

Cognitive behavior therapy for menopausal hot flashes: two case reports

Two case reports of women treated with an individual cognitive behavioral treatment (CBT) for menopausal hot flashes are presented. Both women reported substantial improvements in the number of hot flashes experienced as well as in their quality of life as measured by the Menopause Quality of Life Scale (MENQOL), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Improvements in hot flashes and quality of life were maintained 6 months after treatment ended. It is hypothesized that CBT reduces hot flashes by reducing central sympathetic activation, perceptions of stress, and self-critical thoughts. The long-term efficacy of CBT for hot flashes should be examined in large controlled clinical trials.     

Cigarette smoking, estrogen levels, and hot flashes in midlife women

OBJECTIVE: The aims of this study were to examine the association of smoking with the occurrence, frequency, and severity of hot flashes and to determine whether the mechanism by which active cigarette smoking increases the risk of hot flashes is by lowering estradiol and estrone levels. METHODS: A case-control study was conducted among women aged 45-54 years to examine risk factors for hot flashes. Cases were women who reported ever experiencing hot flashes (n = 353). Controls were women who reported never experiencing hot flashes (n = 258). Each participant completed a questionnaire and provided a blood sample that was used to measure estradiol and estrone levels. RESULTS: The results showed that both current and ever smokers had higher odds than never smokers of experiencing any and more severe hot flashes. Further, significant positive associations were observed between frequency and duration of smoking and the experiencing of any and more severe hot flashes. Smoking was not associated with estradiol or estrone levels in univariate analyses. In addition, the odds ratios for the associations between the cigarette smoking variables and hot flashes did not change when the hormone variables were added to the model. CONCLUSIONS: These findings indicate that smoking is associated with the occurrence of any and more severe hot flashes, independent of estrogen levels.     

Psychological factors associated with sleep disturbance among perimenopausal women

The complex nature of sleep among perimenopausal women warrants a biopsychosocial conceptualization; however, research on the psychological factors that contribute to the increased prevalence of poor sleep quality during this time is limited. We conducted a survey study of perimenopausal women (N = 168) to investigate the relations among nocturnal hot flashes, mood, dysfunctional beliefs and attitudes about sleep (DBAS), and subjective sleep quality. Self-report ratings of depressive symptoms, trait anxiety, hot flashes, and DBAS significantly correlated with poor sleep quality. Ratings on the DBAS Scale-Short Form mediated the relations both between nocturnal hot flashes and sleep quality and between mood and sleep quality. The interplay between physiological and psychological mechanisms among perimenopausal women is highlighted.     

Psychological Factors Associated With Sleep Disturbance Among Perimenopausal Women

The complex nature of sleep among perimenopausal women warrants a biopsychosocial conceptualization; however, research on the psychological factors that contribute to the increased prevalence of poor sleep quality during this time is limited. We conducted a survey study of perimenopausal women (N = 168) to investigate the relations among nocturnal hot flashes, mood, dysfunctional beliefs and attitudes about sleep (DBAS), and subjective sleep quality. Self-report ratings of depressive symptoms, trait anxiety, hot flashes, and DBAS significantly correlated with poor sleep quality. Ratings on the DBAS Scale-Short Form mediated the relations both between nocturnal hot flashes and sleep quality and between mood and sleep quality. The interplay between physiological and psychological mechanisms among perimenopausal women is highlighted.     

Microspectrofluorometric quantitation of autofluorescent lipopigment in the human sympathetic ganglia

The age-related changes in lipopigment autofluorescence were studied by microspectrofluorometry in three different types of human neurons: the sympathetic neurons of the stellate and superior mesenteric ganglion and pyramidal neurons of the frontal cortex. The age-related increase in lipopigment autofluorescence was more rapid in stellate ganglion but similar linear increases were found also in superior mesenteric ganglion and frontal cortex. There was an age-related shift in the autofluorescence from yellow to orange in the ganglia. This may be due to the accumulation of neuromelanin in noradrenergic neurons. Lipopigments were identified in sympathetic neurons at the age of 4 months and all neurons carried pigment granules after the age of 64 years. It is concluded that lipopigment autofluorescence is a useful marker for cellular ageing in both the peripheral and the central nervous system.     

星状神经节阻滞术及其相关应用解剖研究进展

目的：研究星状神经节阻滞术及其相关应用解剖,从而更好地指导临床工作。方法：查阅国内外相关文献,阐述星状神经节及其毗邻结构的解剖关系,分析星状神经节阻滞术式的发展过程及其并发症。结果：星状神经节毗邻众多重要结构,星状神经节阻滞术有一些比较严重的并发症。结论：术者需熟悉星状神经节周围结构以减少并发症,解剖学研究是一个必需的基础。     

Functional anatomy of the major cardiac nerves in cats

In recognition of the extensive use of the cat as an experimental model of cardiac innervation, the effects of electrical stimulation of stellate ganglia, thoracic vagosympathetic complexes, and individual feline cardiopulmonary nerves on heart rate, blood pressure, and contractility in all four cardiac chambers were analysed and correlated with the anatomy of the thoracic autonomic nervous system. The right and left stellate ganglia in cats are relatively large and globular. Distinct dorsal and ventral ansae subclavia arise from these ganglia, connecting with the relatively small, spindle-shaped middle cervical ganglia situated in the apices of the thoracic cage bilaterally. A cranial pole nerve arises from each of the middle cervical ganglia and courses cranially to unite with the ipsilateral superior cervical ganglia. On each side, the major cardiopulmonary nerves arise from the middle cervical ganglion, the relatively large vagosympathetic trunk, and the stellate ganglion. On the right side these nerves consist of a very small right stellate cardiac nerve, a recurrent cardiac nerve, a group of craniovagal nerves and a group of caudovagal cardiopulmonary nerves. On the left side are the left stellate cardiac, ventrolateral, ventromedial, and innominate cardiopulmonary nerves. All of these nerves contain efferent parasympathetic and/or sympathetic fibers which modify cardiac chronotropism and/or inotropism. Some contain afferent fibers. These results indicate that specific cardiopulmonary nerves exist in cats, which when stimulated, modify the cardiovascular system in specific fashions.     

更年期潮热的单胺类神经递质学说

潮热是更年期女性最常见的症状,并且其症状与心血管疾病的发生密切相关,严重影响着更年期女性的身心健康,因此,避免和减轻更年期潮热的发生已经成为当今倍受关注的课题。目前,普遍认为潮热是由下丘脑体温调节中枢功能紊乱所致,但其确切的发病机制尚未阐明。最近的研究相继表明,更年期潮热是雌激素与多种神经递质交互作用的结果,其中单胺类神经递质去甲肾上腺素、5 羟色胺和多巴胺等起到了核心作用,现将其综述如下。     

Baroreceptor-related dysrhythmias in piglets with selective autonomic denervation of the heart

This study was carried out to determine whether selective cardiac autonomic denervation performed on neonatal swine would evoke dysrhythmias later in development. Piglets (n = 27; 5-10 days old) underwent unilateral stellate ganglion ablation, or right cardiac vagotomy, or sham surgery. Fifty to sixty days after denervation, acute experiments were performed to evaluate responses to baroreceptor activation. Of all animals who exhibited prolonged R-R intervals, only those with right stellate ganglion ablation had prolonged corrected QT intervals. Despite findings suggesting an arrhythmogenic state (predominance of left-sided cardiac innervation), dysrhythmias occurred in all animals with stellate ganglion ablation, regardless of laterality, but in few vagotomized or control animals. Our results suggest that partial sympathetic innervation may alter cardiac function so that dysrhythmias are more likely to occur during baroreceptor activation.     

The Role of Spinal Manipulation in Modifying Central Sensitization

Central sensitization (CS) is characterized by adaptations to the central nervous system resulting in decreased sensory thresholds and widespread hypersensitivity. CS is often difficult to manage, with current treatment strategies primarily consisting of medication, pain science education, cognitive behavioral therapy, and graded exercise intervention. Spinal manipulation represents a potential alternative treatment for CS because of its centrally acting neurophysiological mechanisms. However, experimental trials utilizing spinal manipulation in persons with CS often lack the controls or methodology required to determine the technique's effect on meaningful clinical outcomes. This paper summarizes the mechanistic and experimental evidence on spinal manipulation for centrally mediated pain and hypersensitivity, and offers recommendations for future study considerations in this topic area.     

Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs

Many peptides and transmitters found within the brain also have peripheral sites of action. We now demonstrate that the brain releases functionally active neurotransmitters/neuromodulators directly from the brain into the blood through a saturable P-glycoprotein (Pgp) transport system. Downregulating Pgp1 expression with antisense reduced the brain-to-blood transport of morphine, beta-endorphin and other opioids. Lowering Pgp expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood. Similarly, mice with a disruption of the Mdr1a gene were more sensitive to systemic morphine and less sensitive to morphine given centrally. This ability of the Pgp transport system to pump functionally active compounds from the brain to periphery defines a potentially important mechanism for the central nervous system to modulate peripheral systems.     

Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials

OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, is estrogen-like in the skeleton and cardiovascular system and antiestrogenic in reproductive tissues. In contrast to estrogens, raloxifene is not indicated for the treatment of hot flashes. This study was designed to examine the characteristics of hot flashes among healthy postmenopausal women participating in osteoporosis prevention trials who were receiving raloxifene or placebo. METHODS: Adverse event data from three randomized, double-blind trials (N = 876) comparing raloxifene 60 mg/day with placebo for 30 months were integrated and analyzed. Two of the three trials (one European, two North American) were identically designed and were open to healthy postmenopausal women ages 45 through 60 without regard to prior hysterectomy. The third trial was multinational, was open to women ages 40 through 60, and all enrollees had prior hysterectomy at baseline. Women were questioned in general terms about the occurrence of adverse events at 3-6-month intervals. Treatment-emergent adverse events pertaining to hot flashes were included in the current study. RESULTS: At baseline, 12% of women randomly assigned to placebo and 13% assigned to raloxifene reported prevalent hot flashes. After 30 months, the cumulative incidence of hot flashes was 21% for placebo and 28% for raloxifene (P = 0.022), with the difference in incidence rate confined to the first 6 months of therapy. There was no difference between placebo and raloxifene in reported maximum severity of or early discontinuations as a result of hot flashes (< or = 3% per group for both outcomes). Among women whose hot flashes had stopped completely during the 30-month study period, the median total duration of the event prior to becoming symptom-free was 246 days for placebo and 205 days for raloxifene. Among all women reporting a hot flash, the extrapolated total duration of hot flashes was the same for women treated with either raloxifene or placebo. No subgroup-by-therapy interactions were detected. Multivariable regression analysis revealed several factors that were independently weakly predictive of hot flashes. CONCLUSIONS: Raloxifene slightly affects the incidence but not the natural history of hot flashes in healthy postmenopausal women seeking prevention therapy.