Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology

the new data seem to allow a better understanding of how autonomic vulnerability or visceral dysfunction may precipitate or aggravate mental symptoms and disorder.

T. H. Svensson¹

(1)	Department of Pharmacology, Karolinska Institute, Box 60 400, S-104 01 Stockholm, Sweden

Received: 20 June 1986 Revised: 25 November 1986
Psychopharmacology

"Locus coeruleus (LC) is located in the ventrallateral side of the fourth ventricle in the pontine, most of which are noradrenergic neurons projecting to the cortex, cingulate cortex, amygdala nucleus, thalamus, hypothalamus, olfactory tubercles, hippocampus, cerebellum, and spinal cord (Swanson and Hartman, 1975). Norepinephrine (NE) released from the nerve terminal of LC neurons contributes to about 70% of the total extracellular NE in primates brain (Svensson, 1987). It plays important roles not only in arousal, attention, emotion control, and stress (reviewed in Aston-Jones and Cohen, 2005; Berridge and Waterhouse, 2003; Bouret and Sara, 2005; Nieuwenhuis et al., 2005; Sara and Devauges, 1989; Valentino and Van Bockstaele, 2008), but also in sensory information processing (Svensson, 1987). LC directly modulates the somatosensory information from the peripheral system. Under the stress condition, LC could completely inhibit the input from painful stimuli through the descending projection to the spinal cord (Stahl and Briley, 2004). Dys-regulations of LC neurotransmission have been suggested to be involved in physical painful symptoms, attention deficit hyperactivity disorder (ADHD), sleep/arousal disorder, post-traumatic stress disorder, depression, schizophrenia, and Parkinson's disease (reviewed in Berridge and Waterhouse, 2003; Grimbergen et al., 2009; Mehler and Purpura, 2009)."
http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00029/full

reduction in hypothalamic dopamine after sympathectomy, which leads to an increase in serum prolactin level

At this point, it is particularly interesting to recall the earlier reports of middle ear bone remodeling in the gerbil after chemical sympathectomy by guanethidine sulfate (86) or hydroxydopamine (85). Although these neurotoxins do eliminate sympathetic activity, there are, in parallel, major central consequences. In particular, both treatments reduce hypothalamic dopamine, which leads to an increase in serum prolactin levels.

http://ajpendo.physiology.org/content/293/5/E1224.full

"Again, patients admitted with any malignancy, cholecystectomy, thyroidectomy, renal disease, cardiac disease, sympathectomy, or vascular graft were eliminated as controls."

This article reviews the evidence that neuroleptics may increase the risk of breast cancer via their effects on prolactin secretion.
Paul M. Schyve; Francine Smithline; Herbert Y. Meltzer
Neuroleptic-induced Prolactin Level Elevation and Breast Cancer: An Emerging Clinical Issue
Arch Gen Psychiatry, Nov 1978; 35: 1291 - 1301.

Body temperature is highly correlated with plasma prolactin in thermally stressed men
(78), suggesting that normal heat defense is associated with decreased central dopamine, and
intraventricular haloperidol produces a coordinated heat-defense response (79). These reports refute a
unique or essential role for central dopamine antagonism in neuroleptic malignant syndrome hyperthermia
and provide additional evidence that state-dependent factors are important mediators of dopamine
antagonist effects. There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives.

http://ajp.psychiatryonline.org/cgi/content/full/156/2/169

The stellate ganglion has shown to have second and third order neurons that connect with hypothalamus, amygdala, infralimbic, insular and ventromedial temporal cortical regions

"In the course of mapping the sympathetic nervous system to the related regions of the cerebral cortex, Westerhaus and Loewy used pseudorabies virus injections to identify connections of the stellate ganglion. Pseudorabies virus allows identification of neural pathway connections that are 2–3 synapses from the point of injection of the virus. In this manner, the use of pseudorabies virus injection is used to identify cortical areas connected to the stellate ganglion.

The stellate ganglion has shown to have second and third order neurons that connect with hypothalamus, amygdala, infralimbic, insular and ventromedial temporal cortical regions.

These data provides objective, anatomical support for the stellate ganglion interaction with several key structures known to modulate core body temperature, CRPS and PTSD."

http://flipper.diff.org/app/items/info/7052

"Similar low values are observed in patients with sympathectomy and in patients with tetraplegia"

"Patients with progressive autonomic dysfunction (including diabetes) have little or no increase in plasma noradrenaline and this correlates with their orthostatic intolerance (Bannister, Sever and Gross, 1977). In patients with pure autonomic failure, basal levels of noradrenaline are lower than in normal subjects (Polinsky, 1988). Similar low values are observed in patients with sympathectomy and in patients with tetraplegia. (p.51)

The finger wrinkling response is abolished by upper thoracic sympathectomy. The test is also abnormal in some patients with diabetic autonomic dysfunction, the Guillan-Barre syndrome and other peripheral sympathetic dysfunction in limbs. (p.46)

Other causes of autonomic dysfunction without neurological signs include medications, acute autonomic failure, endocrine disease, surgical sympathectomy . (p.100)

Anhidrosis is the usual effect of destruction of sympathetic supply to the face. However about 35% of patients with sympathetic devervation of the face, acessory fibres (reaching the face through the trigeminal system) become hyperactive and hyperhidrosis occurs, occasionally causing the interesting phenomenon of alternating hyperhidrosis and Horner's Syndrome (Ottomo and Heimburger, 1980). (p.159)



Disorders of the Autonomic Nervous System
By David Robertson, Italo Biaggioni
Edition: illustrated
Published by Informa Health Care, 1995
ISBN 3718651467, 9783718651467"



'via Blog this'

Patients with surgical sympathectomies have low plasma levels of DA and NE [49], whereas EPI:NE ratios are increased

Patients with surgical sympathectomies have low plasma levels of DA and NE [49], whereas EPI:NE ratios are increased (unpublished observations), suggesting decreased sympathetically mediated exocytosis and compensatory adrenomedullary activation.   

Catecholamines 101, David S. Goldstein Clin Auton Res (2010) 20:331–352

Low HRV is a risk factor for pathophysiology and psychopathology

http://www.ncbi.nlm.nih.gov/pubmed/18771686

"Most patients note an immediate "calming effect" once the injection is done"

Stellate ganglion blocks have traditionally been done for pain conditions.  However, there is evidence showing some benefits for other conditions such as hyperhydrosis (excessive sweating), hot flashes,  and  painful conditions such as complex regional pain syndrome and atypical facial pain.  The stellate ganglion is the fusion of the inferior cervical ganglion and the first thoracic ganglion that mediate sympathetic fibers, also known as the adrenaline (fight or flight) nerves.  It is thought that PTSD may have sympathetically mediated pathways that are amenable to blocking this nerve structure.  Most patients note an immediate "calming effect" once the injection is done.  Some are even able to stop medications and have social interactions in public that they otherwise would not have been able to do.

http://www.painhonolulu.com/services/stellate-ganglion-blocks-for-ptsd/

Stellate ganglion block alleviates anxiety, depression

Among veterans with post-traumatic stress disorder, treatment with a single stellate ganglion block could help alleviate anxiety, depression and psychological pain rapidly and for long-term use, according to results presented at the American Society for Anesthesiologists Annual Meeting.

See Also

• Experts propose nerve blocks to treat PTSD
• DSM-5 PTSD screening may miss previously diagnosed ...
• Amygdala activation could predict PTSD susceptibility ...

Researchers performed a single right-sided stellate ganglion block (SGB) using 7 mL of 2% lidocaine and 0.25% bupivacaine under fluoroscopic guidance on 12 veterans with military-related, chronic extreme post-traumatic stress disorder (PTSD) with hyperarousal symptoms. At baseline, 1 week, 1 month, 3 months and 6 months post-block, PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS) score and the Post-traumatic Stress Self Report (PSS-SR) scale. Depressive symptoms were assessed with the Beck Depression Inventory version 2. Anxiety related symptoms with a generalized anxiety scale score and the State-Trait Anxiety Index and psychological pain with the Mee-Bunney scale.

Study results showed the block was greatly effective in 75% of participants, with a positive effects taking effect often within minutes of SGB. At week 1, there was significant reduction of both CAPS and PSS-SR and researchers found CAPS approached normal-to-mild PTSD levels by 1 month. Anxiety, depression and psychological pain scores also were significantly reduced by the block, according to study results. Overall, positive effects remained evident at 3 months, but were generally gone by 6 months.

Reference:

Alkire MT. A1046. Presented at: American Society for Anesthesiologists Annual Meeting;  Oct. 11-15, 2014; New Orleans.

http://www.healio.com/psychiatry/ptsd/news/online/%7B14e0a858-100a-43b1-a0e0-47c6376cb885%7D/stellate-ganglion-block-alleviates-anxiety-depression-for-veterans-with-ptsd

Hemodynamic changes in vertebral and carotid arteries were observed after sympathicotomy for hyperhidrosis

T3 sympathicotomy segment was the most frequent transection done (95.83%), as only ablation (25%) or in association with T4 (62.50%) or with T2 (8.33%). It was observed increase in RI and PI of the common carotid artery (p < 0.05). The DPV of internal carotid artery decreased in both sides (p < 0.05). The SPV and the DPV of the right and left vertebral arteries also increased (p < 0.05). Asymmetric findings were observed so that, arteries of the right side were the most frequently affected.
CONCLUSIONS: Hemodynamic changes in vertebral and carotid arteries were observed after sympathicotomy for PH. SPV was the most often altered parameter, mostly in the right side arteries, meaning significant asymmetric changes in carotid and vertebral vessels. Therefore, the research findings deserve further investigations to observe if they have clinical inferences.
http://www.ncbi.nlm.nih.gov/pubmed/16186983

"this hyperhidrosis seems to be reflex, mediated neurologically in the sweating regulatory center in the hypothalamus"

The so called 'compensatory sweating' is NOT compensatory:

"When patients with intense CH are analyzed, we observe that the amount of released sweat seems to be much greater than was that occurring at the primary hyperhidrosis location, not translating a simple compensation or sweating transference from one site to the other. Therefore, this hyperhidrosis seems to be reflex, mediated neurologically in the sweating regulatory center in the hypothalamus.

In order to avoid this neurologically mediated reflex, the sympathetic afferents to the hypothalamus should be restored, allowing negative feedback to block the efferent projection of the sweating regulatory center on the periphery.(14) Therefore, only the reinnervation of the sectioned sympathetic chain could recover this reflex."

http://www.scielo.br/scielo.php?script=sci_arttext&amp;pid=S1806-37132008001100013&amp;lng=en&amp;nrm=iso&amp;tlng=en

https://archive.today/7B795

Jornal Brasileiro de Pneumologia

Print version ISSN 1806-3713

J. bras. pneumol. vol.34 no.11 São Paulo Nov. 2008                        

Guidelines for the prevention, diagnosis and treatment of compensatory hyperhidrosis^*

Roberto de Menezes Lyra^I; José Ribas Milanez de Campos^II; Davi Wen Wei Kang^III; Marcelo de Paula Loureiro^IV; Marcos Bessa Furian^V; Mário Gesteira Costa^VI; Marlos de Souza Coelho^VII

^IThoracic Surgeon. Hospital do Servidor Público Estadual de São Paulo - HSPE/SP, São Paulo Hospital for State Civil Servants - São Paulo, Brazil
^IIAssistant Professor in the Department of Thoracic Surgery. University of São Paulo Hospital das Clínicas, São Paulo, Brazil
^IIIThoracic Surgeon. Hospital Israelita Albert Einstein - HIAE - São Paulo, Brazil
^IVGeneral Surgeon. Hospital Nossa Senhora das Graças, Curitiba, Brazil
^VThoracic Surgeon. Hospital Santa Lúcia, Cruz Alta, Brazil
^VIAdjunct Professor of Surgery. University of Pernambuco School of Medical Sciences, Recife, Brazil
^VIIAdjunct Professor of Surgery. Pontifícia Universidade Católica do Paraná - PUCPR, Pontifical Catholic University of Paraná Curitiba, Brazil

http://bestpractice.bmj.com/best-practice/search.html?searchableText=Hyperhidrosis&amp;aliasHandle=guidelines&amp;languageCode=en

https://archive.today/0UXdW

distinct patterns of peripheral physiological activity are associated with different emotion

Int J Psychophysiol. 2006 Jul;61(1):5-18. Epub 2006 Jan 24.

Basic emotions are associated with distinct patterns of cardiorespiratory activity.

Rainville P1, Bechara A, Naqvi N, Damasio AR.

Author information

Abstract

The existence of specific somatic states associated with different emotions remains controversial. In this study, we investigated the profile of cardiorespiratory activity during the experience of fear, anger, sadness and happiness. ECG and respiratory activity was recorded in 43 healthy volunteers during the recall and experiential reliving of one or two potent emotional autobiographical episodes and a neutral episode. Univariate statistics indicated that the four emotions differed from each other and from the neutral control condition on several linear and spectral indices of cardiorespiratory activity. Dependent variables were further reduced to five physiologically meaningful factors using an exploratory principal component analysis (PCA). Multivariate analyses of variance and effect size estimates calculated on those factors confirmed the differences between the four emotion conditions. A stepwise discriminant analyses predicting emotions using the PCA factors led to a classification rate of 65.3% for the four emotions (chance=25%; p=0.001) and of 72.0-83.3% for pair-wise discrimination (chance=50%; p's<0.05). These findings may be considered preliminary in view of the small sample on which the multivariate approach has been applied. However, this study emphasizes the need to better characterize the multidimensional factors involved in cardio-respiratory regulation during emotion. These results are consistent with the notion that distinct patterns of peripheral physiological activity are associated with different emotions. 
http://www.ncbi.nlm.nih.gov/pubmed/16439033

http://books.google.com.au/books?id=Qf6-BsHA5SoC&pg=PA295&lpg=PA295&dq=distinct+patterns+of+peripheral+physiological+activity+are+associated+with+different+emotion&source=bl&ots=JCNuxgiRgf&sig=3kJK19DDICal-9xQoJCC4S0MlbI&hl=en&sa=X&ei=uUArVL6UNNXfoASRkILwAw&ved=0CDgQ6AEwAw#v=onepage&q=distinct%20patterns%20of%20peripheral%20physiological%20activity%20are%20associated%20with%20different%20emotion&f=false

Depletion of peripheral sympathetic noradrenaline led to significant decrements in escape and avoidance responding

PsycNET - Option to Buy: "Chemical sympathectomy and avoidance learning in the rat.

By Di Giusto, E. L.; King, M. G.
Journal of Comparative and Physiological Psychology, Vol 81(3), Dec 1972, 491-500.
Abstract
Reports results of 5 experiments with male Wistar rats (N = 108). Depletion of peripheral sympathetic noradrenaline induced by administration of 6-hydroxydopamine, ip, led to significant decrements in escape and avoidance responding when the required response was difficult, but not when it was relatively easy to acquire. Results are similar to previous findings obtained with adrenal-demedullated Ss. Findings clarify the role of the sympathetic nervous system in the motivation of behavior elicited by aversive stimulation. Implications for 2-process theory and the "Kamin effect," or "learned helplessness," are discussed. (40 ref.) (PsycINFO Database Record (c) 2012 APA, all rights reserved)"

effect of bilateral cervical sympathetic ganglionectomy on the architecture of pial arteries

The influence of the cranial sympathetic nerves on the architecture of pial arteries in normo- and hypertension was examined. For this purpose the effect of bilateral superior cervical ganglionectomy was evaluated in normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). The operations were performed at the age of 1 wk, which is just prior to the onset of ganglionic transmission. The length of the inner media contour was measured and the media cross-sectional area was determined planimetrically, with computerized digitalization of projected photographic images of transversely sectioned pial arteries. Four wk after sympathectomy there was a 20% reduction in media cross-sectional area and a consequent reduction in the ratio between media area and calculated luminal radius in the major pial arteries at the base of the brain in WKY but not in SHRSP. Conversely, in small pial arteries linear regression analysis showed that in WKY subjected to ganglionectomy the relationship between media cross-sectional area and luminal radius was significantly larger in arteries with a radius less than 21 microns compared to untreated WKY. No such effect was seen in the corresponding SHRSP vessels. In addition, the cross-sectional area of the internal elastic membrane (IEM) in the basilar arteries of WKY was measured by means of a computerized image-analysing system. Mean cross-sectional area of the IEM was approximately 45% larger following SE than in control animals. The present findings propose a 'trophic' role for the sympathetic perivascular nerves in large pial arteries of the rat. The increased media-radius ratio in the small pial arteries of the WKY following sympathectomy might reflect a compensatory hypertrophy due to reduced protection from the larger arteries against the pressure load. The inability to detect any morphometrically measurable effect of the sympathectomy in the cerebral arteries of SHRSP is probably explained by a marked growth-stimulating effect of the high pressure load in these animals.

http://www.ncbi.nlm.nih.gov/pubmed/7701941

bilateral ganglionectomy resulted in minor decreases in the cerebrovascular contents of ACh

The effects of uni- or bilateral surgical ablation of the SPG, a putative origin of the cholinergic cerebrovascular innervation, were investigated on these two specific cholinergic markers at various postoperative times. ChAT activity and ACh levels were enriched in the cerebral as compared to the peripheral arteries. Among the cerebrovascular tissues tested, ACh levels were particularly high in the circle of Willis and the vertebrobasilar segments and, to a lesser extent, in the middle cerebral artery. Lower levels were found in the small pial vessels and choroid plexus. Overall, ChAT activity measured in different arterial beds paralleled the distribution of ACh. Following uni- or bilateral removal of the SPG, slight reductions were observed in ChAT activity in rostral cerebral arteries and pial vessels overlying the frontal cortex. Similarly, bilateral ganglionectomy resulted in minor decreases in the cerebrovascular contents of ACh in these same vascular segments.

J Cereb Blood Flow Metab. 1991 Mar;11(2):253-60.

Regional cerebral blood flow correlates with heart period and high-frequency heart period variability

Psychophysiology. 2004 Jul;41(4):521-30.

Regional cerebral blood flow correlates with heart period and high-frequency heart period variability during working-memory tasks: Implications for the cortical and subcortical regulation of cardiac autonomic activity.

Gianaros PJ1, Van Der Veen FM, Jennings JR.

Author information

Erratum in

• Psychophysiology. 2004 Sep;41(5):807.

Abstract

The aim of the present study was to characterize the functional relationships between behaviorally evoked regional brain activation and cardiac autonomic activity in humans. Concurrent estimates of regional cerebral blood flow (rCBF; obtained by positron emission tomography), heart period, and high-frequency heart period variability (HF-HPV; an indicator of cardiac parasympathetic activity) were examined in 93 adults (aged 50-70 years) who performed a series of increasingly difficult working-memory tasks. Increased task difficulty resulted in decreased heart period (indicating cardioacceleration) and decreased HF-HPV (indicating decreased cardiac parasympathetic activity). Task-induced decreases in heart period and HF-HPV were associated with concurrent increases and decreases in rCBF to cortical and subcortical brain regions that are speculated to regulate cardiac autonomic activity during behavioral processes: the medial-prefrontal, insular, and anterior cingulate cortices, the amygdala-hippocampal complex, and the cerebellum. These findings replicate and extend a small number of functional neuroimaging studies that suggest an important role for both cortical and subcortical brain systems in human cardiac autonomic regulation.

http://www.ncbi.nlm.nih.gov/pubmed/15189475

after sympathectomy "He becomes more quiet, less impressionable, less agitated, tremor diminishes..."

Everyone seems to agree that when sympathectomy is successful the subjective symptoms of the patient show a considerable improvement. He becomes more quiet, less impressionable, less agitated, tremor diminishes, tachycardia, however, is little influenced or not at all, and the same is true for goiter.
   In conclusion it may be said that the results obtained from sympathectomy when present are very immediate. The ocular symptoms are the ones most happily influenced by the operation; the others such as nervousness, tachycardia, and goiter are problematical.
   Remote Results.- In going over the cases operated by Jaboulay as far back as twelve and fourteen years, A. Charlier was able to find that a number of his patients had been cured completely. He was able to retrace 18 out of the 31 cases operated by Jaboulay from four to fourteen years before. Three of them were completely cured, 9 of them were so ameliorated that the subjective cure was a complete one, the objective cure, however, being incomplete; the 6 remaining cases were doubtful. All these patients experienced considerable benefit to their nervous symptoms; improved and no trophic disturbances of any sort followed as the result of sympathectomy.

Title	Thyroid and Thymus
Author	André Crotti
Publisher	Lea & Febiger, 1918
Original from	Harvard University
Digitized	17 Dec 2007
Length	567 pages

An absence of afferent feedback concerning autonomically generated bodily states was associated with subtle impairments of emotional responses

nature neuroscience • volume 4 no 2 • february 2001 

Neuroanatomical basis for first- and second-order representations of bodily states
H. D. Critchley1,2, C. J. Mathias2,3 and R. J. Dolan1

The Effects of Thoracic Sympathotomy on Heart Rate Variability in Patients with Palmar Hyperhidrosis

Compared with preoperative variables, there was a significant increase in the number of adjacent normal R wave to R wave (R- R) intervals that differed by more than 50 ms, as percent of the total number of normal RR intervals (pNN50); root mean square difference, the square root of the mean of the sum of squared differences between adjacent normal RR intervals over the entire 24-hour recording; standard deviation of the average normal RR in- terval for all 5-minute segments of a 24-hour recording (SDANN) after thoracic sympathotomy. Low frequencies (LF, 0.04 to 0.15 Hz) decreased significantly.
Yonsei Med J 53(6):1081-1084, 2012

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481380/pdf/ymj-53-1081.pdf 

anatomical variations

"denervation of the T2-T3 thoracic sympathetic ganglia extends to the craniofacial region in 20.75% of cases, an area that is classically attributed to node T1."

Bronconeumol. 2003, 39: 19-22. - Vol 39 Núm.01

Patients with surgical sympathectomies have low plasma levels of DA and NE [49], whereas EPI:NE ratios are increased

Patients with surgical sympathectomies have low plasma levels of DA and NE [49], whereas EPI:NE ratios are increased (unpublished observations), suggesting decreased sympathetically mediated exocytosis and compensatory adrenomedullary activation.

Catecholamines 101, David S. Goldstein
Clin Auton Res (2010) 20:331–352

The Change in Regional Cerebral Oxygen Saturation after Stellate Ganglion Block

The Change in Regional Cerebral Oxygen Saturation after Stellate Ganglion Block: "Korean J Pain. Jun 2010; 23(2): 142–146.
Published online May 31, 2010.



Background

Stellate ganglion block (SGB) is known to increase blood flow to the innervations area of the stellate ganglion. Near infrared spectroscopy reflects an increased blood volume and allows continuous, non-invasive, and bedside monitoring of regional cerebral oxygen saturation (rSO2). We investigated the influence of SGB on bilateral cerebral oxygenation using a near infrared spectroscopy.



Methods

SGB was performed on 30 patients with 1% lidocaine 10 ml using a paratracheal technique at the C6 level and confirmed by the presence of Horner's syndrome. The blood pressure (BP), heart rate (HR) and rSO2 were measured before SGB and 5, 10, 15 and 20 minutes after SGB. Tympanic temperature of each ear was measured prior to SGB and 20 minutes after SGB.



Results

The increments of the rSO2 on the block side from the baseline were statistically significant at 5, 10, 15 and 20 minutes. The rSO2 on the non-block side compared with the baseline, however, decreased at 15 and 20 minutes. The difference between the block and the non-block sides was significant at 15 and 20 minutes. The BP at 10, 15 and 20 minutes was increased and the HR was increased at 10 and 15 minutes.



Conclusions

We observed an increment of the rSO2 on the block side from the baseline; however, the rSO2 on the non-block side decreased."

Local distribution of the effects of sympathetic stimulation on cerebral blood flow in the rat

Local distribution of the effects of sympathetic s... [Brain Res. 1990] - PubMed - NCBI: "Although the density of sympathetic fibres on the cerebral vessels varies regionally, the cerebral circulatory effects of electrical stimulation of these fibres on the cerebral circulation have not been mapped in detail. In the present study the effects of sympathetic stimulation on local cerebral blood flow were examined in urethane anaesthetized rats using autoradiographic techniques. Initial experiments determined that unilateral stimulation of the superior cervical ganglion altered cerebral circulatory dynamics to an extent sufficient to reduce cerebral venous pressure by 1.1 +/- 0.2 mm Hg. Local cerebral blood flow was measured with iodo[14C]antipyrine autoradiography in 4 groups: (1) sham; (2) sham + unilateral sympathetic nerve section; (3) unilateral stimulation of the superior cervical ganglion; and (4) unilateral sympathetic stimulation + contralateral sympathetic nerve section. In the sham animals, local cerebral blood flow was equivalent in the innervated and denervated hemispheres. During stimulation plus contralateral nerve section, a regionally heterogeneous response to sympathetic stimulation was observed. Local cerebral blood flow was reduced 11-19% on the stimulated side in over one half (15/28) of the regions examined (e.g. thalamic nuclei and caudate nucleus). In general, ipsilateral reductions in flow occurred in the territory supplied by the middle cerebral, posterior cerebral and posterior communicating arteries and their branches. Cerebral blood flow was symmetrical in regions supplied by the basilar and anterior cerebral arteries and in some midline structures."

Effects of stellate ganglion block on cerebral haemodynamics as assessed by transcranial Doppler ultrasonography

Background. Stellate ganglion block (SGB) causes vasodilatation in the skin of the head and neck

because of regional sympathetic block. Its effects on cerebral haemodynamics, in health or in

disease, are not clear. We evaluated the effects of SGB on ipsilateral middle cerebral artery flow

velocity (MCAFV), estimated cerebral perfusion pressure (eCPP), zero flow pressure (ZFP),

carbon dioxide reactivity (CO2R) and cerebral autoregulation using transcranial Doppler

ultrasonography (TCD).



Methods. Twenty male patients, with pre-existing brachial plexus injury, and undergoing SGB for

the treatment of complex regional pain syndrome of the upper limb, were studied. For SGB, 10 ml

of plain lidocaine 2% was used and the onset of block was confirmed by presence of ipsilateral

Horner’s syndrome. The MCAFV, eCPP, ZFP, CO2R, and cerebral autoregulation were assessed

before and after SGB using established TCD methods. The changes in these variables were

analysed using Wilcoxon’s signed rank test.



Results. The block caused a significant decrease in MCAFV from median (inter-quartile range)

value of 61 (53, 67) to 55 (46, 60) cm s 1, a significant increase in eCPP from 59 (51, 67) to

70 (60, 78) mm Hg, and a significant decrease in ZFP from 32 (26, 39) to 25 (16, 30) mm Hg. There

were no significant changes in CO2R or cerebral autoregulation.

http://bja.oxfordjournals.org/content/95/5/669.full.pdf

NE is critical for the acquisition of spatial working memory

The adrenergic system (utilizing norepinephrine, NE, as a neurotransmitter) is implicated in hippocampus-based learning and memory, in addition to its well known peripheral actions mediated by the sympathetic nervous system.

Using a more standard variation of the above protocol on the radial arm maze, we used this apparatus to test the role of NE in spatial working memory. We found significant, robust differences between Dbh-/- and Dbh+/- mice after a training period of approximately 14 days. To test whether this difference was due to a potential deficit in acquisition or performance, we restored NE in Dbh-/- mice by administering the synthetic precursor L-DOPS after four days of stable behavioral differences between genotypes. In a separate trial, we also restored NE signaling with dexmedetomidine, a selective alpha-2 receptor agonist. A gradual improvement by Dbh-/- mice to levels comparable to Dbh+/- mice indicated that NE is critical for the acquisition of spatial working memory, and suggested a role for the alpha-2 adrenergic receptor in the processing of spatial working memory.

Suggested Citation

Gertner, Michael J. and Thomas, Steven A., "The role of norepinephrine in spatial reference and spatial working memory" 08 June 2006. CUREJ: College Undergraduate Research Electronic Journal, University of Pennsylvania, http://repository.upenn.edu/curej/18.

Date Posted: 08 June 2006

This document has been peer reviewed.

Michael J. Gertner, University of Pennsylvania
Steven A. Thomas, University of Pennsylvania
http://repository.upenn.edu/curej/18/

Inflammation in dorsal root ganglia after peripheral nerve injury: Effects of the sympathetic innervation

Following a peripheral nerve injury, a sterile inflammation develops in sympathetic and dorsal root ganglia (DRGs) with axons that project in the damaged nerve trunk. Macrophages and T-lymphocytes invade these gan- glia where they are believed to release cytokines that lead to hyperexcitability and ectopic discharge, possibly contributing to neuropathic pain. Here, we examined the role of the sympathetic innervation in the inflammation of L5 DRGs of Wistar rats following transection of the sciatic nerve, comparing the effects of specific surgical in- terventions 10–14 days prior to the nerve lesion with those of chronic administration of adrenoceptor antago- nists. Immunohistochemistry was used to define the invading immune cell populations 7 days after sciatic transection. Removal of sympathetic activity in the hind limb by transecting the preganglionic input to the rele- vant lumbar sympathetic ganglia (ipsi- or bilateral decentralization) or by ipsilateral removal of these ganglia with degeneration of postganglionic axons (denervation), caused less DRG inflammation than occurred after a sham sympathectomy. By contrast, denervation of the lymph node draining the lesion site potentiated T-cell in- flux. Systemic treatment with antagonists of α1-adrenoceptors (prazosin) or β-adrenoceptors (propranolol) led to opposite but unexpected effects on infiltration of DRGs after sciatic transection. Prazosin potentiated the influx of macrophages and CD4+ T-lymphocytes whereas propranolol tended to reduce immune cell invasion. These data are hard to reconcile with many in vitro studies in which catecholamines acting mainly via β2-adrenoceptors have inhibited the activation and proliferation of immune cells following an inflamma- tory challenge. 

Autonomic Neuroscience: Basic and Clinical 182 (2014) 108–117 

Neuroscience Research Australia, Randwick, NSW 2031, and the University of New South Wales, Sydney, NSW 2052, Australia 

electric stimulation of the sympathetic cord in the upper thoracic level on the middle cerebral artery blood flow velocity

The effect of electric stimulation of the sympathetic cord in the upper thoracic level on the middle cerebral artery blood flow velocity (V(MCA)) in humans was examined using transcranial Doppler sonography monitoring during surgery for palmar hyperhidrosis. Sympathetic stimulation resulted in marked and rapid increases Of V(MCA). The responses were preceded by prompt increases of mean arterial blood pressure (MABP) and heart rate (HR). Division of the sympathetic cord cranially or caudally to the stimulation site partially reduced the V(MCA), MABP and HR responses. Both these operations reduced sympathetic pathways to the heart as reflected by a decrease in HR and MABP. The integrity of the sympathetic pathway from the stimulation site through the superior cervical ganglion and the carotid plexus was not a prerequisite for a V(MCA) response. Our data suggest that the V(MCA) increase mainly results from stimulation of the heart and the cardiovascular system, resulting in marked increases of blood pressure and heart rate.

CEREBROVASCULAR DISEASES Volume: 2 Issue: 6 Pages: 359-364 Published: NOV-DEC 1992

Treatment of social phobia by endoscopic thoracic sympathicotomy

Eur J Surg Suppl. 1998;(580):27-32.

Treatment of social phobia by endoscopic thoracic sympathicotomy.

Telaranta T.

THE PATHOGNOMONIC SYMPTOMS OF SOCIAL PHOBIA: HYPERHIDROSIS, PALPITATION, BLUSHING, TREMOR, AND ANXIETY, WERE ALL HIGHLY SIGNIFICANTLY (P < 0.001) ALLEVIATED BY ETS. 88% OF THE PATIENTS WERE SATISFIED WITH THE RESULT. THERE WERE NO COMPLICATIONS.

CONCLUSION:

ETS seems a promising alternative to conservative therapy for social phobia.

Can J Anaesth. 2002 Aug-Sep;49(7):758-9.

Unexpected beneficial effect of stellate ganglion block in a schizophrenic patient.

Takano M, Takano Y, Sato I.

http://www.ncbi.nlm.nih.gov/pubmed/12193502

Jpn J Ophthalmol. 2006 Nov-Dec;50(6):567-9.

Visual hallucinations following stellate ganglion block in a patient with central retinal artery occlusion.

Kurimoto T, Takata M, Nishimura M, Tagami Y, Okamoto N, Mimura O.

http://www.ncbi.nlm.nih.gov/pubmed/17180540

Masui. 1993 Nov;42(11):1696-8.

[Three case reports of the use of stellate ganglion block for the climacteric psychosis].

Ikeda K1, Isshiki A, Yoshimatsu N, Oumi A, Ito S, Ikeda T.

Author information

Abstract

There are many reports of the use of stellate ganglion block (SGB) for the climacteric psychosis, which is considered to be sympathicotonic response to stress. We experienced three cases of the SGB therapy for the climacteric psychosis. We performed SGB three times per week by 1% lidocaine 5 ml, and observed improvements of the symptoms after doing SGB for five times. The patients reported psychological relaxation after receiving SGB therapy. We examined the changes of the serum concentrations of ACTH, LH, FSH, and catecholamines (epinephrine, norepinephrine) before and after SGB in 8 patients who were suffering from climacteric psychosis, because we wanted to know the endocrinological response to SGB. We observed a significant decrease in norepinephrine concentration after SGB, which is reasonable considering the sympathetic blockage. There were no significant changes of ACTH, LH, FSH, and epinephrine. We conclude that SGB therapy must be effective for the climacteric psychosis because of sympathetic blockade. But we could not clarify the influence of endocrinological response to SGB.

"lowering of heart rate and blood pressure, decreased responsiveness of the cardiocirculatory system to emotional stimuli after sympathectomy

"lowering of heart rate and blood pressure, decreased responsiveness of the cardiocirculatory system to emotional stimuli: it is an effect that is especially noticeable in patients operated on for erythrophobia and less evident in those operated for hyperhidrosis. It is almost always a welcome phenomenon, which contributes considerably to the feeling of tranquility and serenity that generally supersedes anxiety. Excessive reduction in blood pressure or heart rate may lead to a state of weakness and fatigue that may require removal of the clips in approx. 2%. This rare state of asthenia contrasts with the increased energy and vigor that most patients experience when they feel freed from overwhelming anxiety."    

"The neurovegetative nervous system is, however, very dynamic and tends to adapt continuously during lifetime to all environmental or organic changes and conditions. Therefore, it reacts very individually when a reflex circuit has been blocked. The resulting side effects cannot be predicted in detail, and though they in most patients are relatively mild or even absent, there is a small group of patients developing heavy side effects. Therefore, surgery should only be considered in carefully selected cases in whom non-invasive treatment has failed and in whom the detrimental consequences of erythrophobia regarding the psychosocial situation and the quality of life is such to justify more adverse side effects. It should also always be kept in mind that therapy can be ineffective and that, in the long term, 10-15% of patients do not consider themselves satisfied with the result of surgery. In any case, the author prefers the use of a potentially reversible surgical technique (ESB), instead of destructive techniques (cutting, coagulation, removal of ganglia)."  

http://www.chir.it/en_erythrophobia.php

significant associations between heart rate and regional cerebral blood flow

Neurosci Biobehav Rev. 2012 Feb;36(2):747-56. doi: 10.1016/j.neubiorev.2011.11.009. Epub 2011 Dec 8.

A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health.

The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model and update it with recent results. Specifically, we performed a meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow. We identified a number of regions, including the amygdala and ventromedial prefrontal cortex, in which significant associations across studies were found. We further propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. Heart rate variability may provide an index of how strongly 'top-down' appraisals, mediated by cortical-subcortical pathways, shape brainstem activity and autonomic responses in the body. If the default response to uncertainty is the threat response, as we propose here, contextual information represented in 'appraisal' systems may be necessary to overcome this bias during daily life. Thus, HRV may serve as a proxy for 'vertical integration' of the brain mechanisms that guide flexible control over behavior with peripheral physiology, and as such provides an important window into understanding stress and health.

http://www.ncbi.nlm.nih.gov/pubmed/22178086

important relationship among cognitive performance, HRV, and prefrontal neural function

"These findings in total suggest an important relationship among cognitive performance, HRV, and prefrontal neural function that has important implications for both physical and mental health. Future studies are needed to determine exactly which executive functions are associated with individual differences in HRV in a wider range of situations and populations."

http://www.ncbi.nlm.nih.gov/pubmed/19424767

The sympathoadrenal system is one of the major pathways mediating physiological responses in the organism

The sympathoadrenal system is one of the major pathways mediating physiological responsesin the organism. The sympathoadrenal system plays an important role in the regulation of blood pressure, glucose, sodium and other key physiological and metabolic processes. In many disease states, the sympathoadrenal system is affected and by corrective physiological responses the sympathoadrenal system preserves homeostasis. Many therapeutic agents are either adrenergic activators or inhibitors. Therefore, measurements of the components of the sympathoadrenal system and the activity of the sympathoadrenal system have been of major interest for decades.

Levels of plasma (p-) noradrenaline (NA), the sympathetic neurotransmitter, have been used to indicate activity of the neuronal sympathoadrenal component, while adrenaline (Adr) levels indicate activity of the hormonal adrenomedullary component of the sympathoadrenal system (Christensen 1991, Goldstein 1995, Christensen & Norsk 2000).

Based upon the absence of an arterio-venous increase in p-DOPA concentration in sympathectomized limbs and a decrease in p-DOPA after inhibition of tyrosine hydroxylase (TH) in dogs, it was concluded that DOPA can pass across sympathetic neuronal membranes to reach the general circulation and furthermore, that p-DOPA may be related to regional rate of tyrosine hydroxylation (Goldstein et al 1987a). P-DOPA only demonstrated minimal changes during stimuli that produced significant changes in p-NA. Due to partly parallel changes of p-NA and p-DOPA, however, it was believed that p-DOPA reflect the rate of catecholamine synthesis and that p-DOPA was a simple and direct index of TH activity in vivo (Eisenhofer et al 1988, Goldstein & Eisenhofer 1988, Garty et al 1989b). It was inferred that p-DOPA levels may be an index of sympathetic activity.

Department of Internal Medicine and Endocrinology, Herlev University Hospital, Herlev.

Correspondence: Ebbe Eldrup, Bolbrovænge 29, DK-2960 Rungsted Kyst.

Official opponents: Jens H. Henriksen, professor, MD, and Jan Abrahamsen, MD.

Dan Med Bull 2004;51:34-62.

"Sympathectomy can enhance or suppress antibody production"

Neuropsychiatry - Google Books: Neuropsychiatry
 edited by Randolph B. Schiffer, Stephen M. Rao, Barry S. Fogel

Stellate Ganglion Block for the Treatment of Posttraumatic Stress Disorder | Psychiatric Annals

Stellate Ganglion Block for the Treatment of Posttraumatic Stress Disorder | Psychiatric Annals: "SGB has been shown to have utility for diagnostic, therapeutic, and prognostic purposes for a variety of conditions, including: chronic regional pain syndrome types I and II to the upper extremities (CRPS I and II); chronic and acute vascular insufficiency/occlusive vascular disorders of the upper extremities, such as Raynaud’s disease, intra-arterial embolization and vasospasm. SGB has also been found an effective treatment for poor lymphatic drainage and local edema of the upper extremity following breast surgery; postherpetic neuralgia; and phantom limb pain or amputation stump pain. Patients with quinine poisoning; sudden hearing loss and tinnitus; hyperhidrosis of the upper extremity; cardiac arrhythmias and ischemic cardiac pain; Bell’s palsy and a variety of orofacial pain syndromes, including neuropathic orofacial pain and trigeminal neuralgia; vascular headache such as cluster and migraine headaches; and neuropathic pain syndromes among cancer patients are all also candidates for SGB.2,3,12–16

SGB has also been recommended for improving blood flow to the cranium for angiography and following stroke/cerebrovascular accident and hyperhidrosis to the upper extremities.13,14 Additionally, SGB’s use has been reported in the treatment of Ménière’s syndrome3 and hot flashes.17–19"



https://archive.today/yOe5b

Sympathectomy causes wall thinning, elongation, convolution, and aneurysm formation

"Sympathectomy causes basilar artery enlargment, which is beneficial for maintaining cerebral blood flow; however, it also causes wall thinning, elongation, convolution, and aneurysm formation, which may be hazardous in stenoocclusive carotid artery disease. Sympathectomy can prevent new vessel formation and hyperthyrophic changes at the posterior circulation. Neovascularisation is not detected adequately in sympathectomised animals."



Acta Neurochirurgica156.5 (May 2014): 963-9.

epinephrine modulates brain limbic structures to encode and store new information

The excitatory actions of epinephrine were not observed

The excitatory actions of epinephrine were not observed in groups given an identical dose of the hormone after peripheral β-adrenergic receptor blockade with sotalol. These findings demonstrate that neural discharge in vagal afferent fibers is increased by elevations in peripheral concentrations of epinephrine and the significance of these findings in understanding how epinephrine modulates brain limbic structures to encode and store new information into memory is discussed.

Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral β-adrenergic receptors

T. Miyashita and C.L. Williams

^aDepartment of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA
^bDepartment of Psychology, The University of Virginia, Charlottesville, VA 22904, USA

Received 9 June 2005; 

revised 17 August 2005; 

accepted 29 August 2005. 

Available online 17 October 2005.