BACKGROUND: Upper thoracic sympathectomy is used to treat several disorders. Sympathetic nerve fibers emanating from thoracic ganglia innervate the heart. Whether unilateral or bilateral upper thoracic sympathectomy affects cardiac sympathetic innervation in humans in vivo has been unclear. OBJECTIVES: The purpose of this study was to assess whether thoracic sympathectomy decreases cardiac sympathetic innervation, as indicated by positron emission tomographic scanning after intravenous injection of the sympathoneural imaging agent 6-[18F]fluorodopamine. METHODS: Nine patients with previous upper thoracic sympathectomies (four right-sided, one left-sided, four bilateral) underwent thoracic 6-[18F]fluorodopamine scanning between 1 and 2 hours after injection of the imaging agent. In each case, a low rate of entry of norepinephrine into the arm venous drainage (norepinephrine spillover) verified upper limb sympathectomy. Data were compared with those from the interventricular septum of patients with cardiac sympathetic denervation associated with pure autonomic failure and from normal volunteers. RESULTS: All four patients with bilateral sympathectomy had low septal myocardial 6-[18F]fluorodopamine-derived radioactivity (2,673 +/- 92 nCi-kg/cc-mCi at an average of 89 minutes after injection) compared with normal volunteers (3,634 +/- 311 nCi-kg/cc-mCi at 83 minutes, N = 22, P = .007) and higher radioactivity than in patients with pure autonomic failure (1,320 +/- 300 nCi-kg/cc-mCi at 83 minutes, N = 7, P = .003). Patients with unilateral sympathectomy had normal 6-[18F]fluorodopamine-derived radioactivity (3,971 +/- 337 nCi-kg/cc-mCi at 87 minutes). CONCLUSIONS: Bilateral upper thoracic sympathectomy partly decreases cardiac sympathetic innervation density.
Sunday, April 13, 2008
Aberrant regeneration following sympathectomy - Frey's Syndrome
Physiological gustatory facial sweating and flushing commonly occur in response to eating spicy foods containing capsacin. This response, combined with salivation, lacrimation, and nasal secretion occurs more easily in warm climates where sweat glands are already at a subthreshold level of excitaiton for thermal sweating (Lee 1954).
The pattern is symmetrical with sweating involving the head and exceptionally the neck, and with flushing most apparent in the nose and cheek (Haxton 1948; Monro 1959, Fox et al. 1962; Drummond and Lance 1987).
Aberrant regeneration following sympathectomy can give rise to pathological gustatory facial flushing and sweating. Weeks, months, or years after cervicothoracic preganglionic sympathectomy, gustatory sweating and flushing may develop on the denervated side along with impaired thermoregulatory sweating. (Bloor 1969; Kurchin at al. 1977)
Sympathetic preganglionic fibers originally destined for the salivary glands may be responsible through faulty reinnervation of the stellate ganglion... (Bloor, 1969; Drummond and Lance 1987).
Interruption of postganglionic sympathetic facial fibers may render residual neurilemmal sheaths and sympathetic endings susceptible to stray collateral sprouting or faulty regeneration of parasympathetic fibers that normally mediate salivation.
The pattern is symmetrical with sweating involving the head and exceptionally the neck, and with flushing most apparent in the nose and cheek (Haxton 1948; Monro 1959, Fox et al. 1962; Drummond and Lance 1987).
Aberrant regeneration following sympathectomy can give rise to pathological gustatory facial flushing and sweating. Weeks, months, or years after cervicothoracic preganglionic sympathectomy, gustatory sweating and flushing may develop on the denervated side along with impaired thermoregulatory sweating. (Bloor 1969; Kurchin at al. 1977)
Sympathetic preganglionic fibers originally destined for the salivary glands may be responsible through faulty reinnervation of the stellate ganglion... (Bloor, 1969; Drummond and Lance 1987).
Interruption of postganglionic sympathetic facial fibers may render residual neurilemmal sheaths and sympathetic endings susceptible to stray collateral sprouting or faulty regeneration of parasympathetic fibers that normally mediate salivation.
Pathological gustatory sweating and flushing can develop
after injury to preganglionic cervicothoracie sympathetic fibres, an
unavoidable consequence of resecting that part of the sympathetic chain. The
mechanism of this abnormal response is uncertain; conceivably, though,
regeneration of injured salivatory fibres or collateral sprouting from nearby
intact fibres creates aberrant connections between salivatory fibres and
denervated vasomotor and sudomotor neurons in the superior cervical ganglion. 7
Commands to salivate would then be translated into commands to sweat and flush
in the distribution of sympathetic denervation. Cross-innervation lower down in
the stellate ganglion can also produce unusual and potentially distressing
autonomic disturbances in the sympathetically denervated arm (e.g.
piloerection while eating)
P.D.DRUMMOND
School of Psychology, Murdoch University,
South Street, Murdoch,
Chronic Idiopathic Anhidrosis - Consequence of Sympathectomy
Chronic Idiopathic Anhidrosis is a syndrome of unknown etiology - a heat intolerance that correlates with generalized or regional sweating defects.
gustatory sweating occurred in 32% of patients
The questionnaire was returned by 96% of patients after a median of 17 months. Overall, gustatory sweating occurred in 32% of patients, and the incidence was significantly associated with extent of sympathectomy (p = 0.04). However, because the extent of sympathectomy was always decided by the location of primary hyperhidrosis, the latter may also explain the risk of gustatory sweating.
Gustatory Side Effects After Thoracoscopic Sympathectomy
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T11-4J963XN-1R&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7cad987402b12485375284dc221ec19b
NE Loss Causes Motor Impairment
Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice
Departments of *Human Genetics and Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322; and Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
Edited by Richard D. Palmiter, University of Washington School of Medicine, Seattle, WA, and approved June 25, 2007 (received for review March 27, 2007)
http://www.pnas.org/cgi/content/full/104/34/13804
NE Loss Causes Motor Impairment. We suggest two possible mechanisms for the motor impairments of Dbh–/– and LC-lesioned mice. SI Fig. 6).
Depression of T cell immunity following chemical sympathectomy
Alterations in Sympathetic Noradrenergic Innervation in Lymphoid ...
Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and in vitro following chemical sympathectomy. Brain Behav. ...www.annalsnyas.org/cgi/content/full/840/1/262
depletion of brain noradrenaline levels causes a disturbance in cerebral microvascular tone
| Thirty male Wistar rats, weighing 350 to 400 gm each, received stereotactic injections of 6-hydroxydopamine (300 micrograms/kg) into the left lateral ventricle. The same amount of saline was injected into a control group of 15 rats. Seven days after this procedure, cerebral blood flow (CBF) was measured by the hydrogen clearance method. A hypertensive condition at a mean arterial pressure of about 160 mm Hg was maintained for 1 hour by intravenous infusion of phenylephrine. In the 6-hydroxydopamine-treated group, CBF increased significantly after the elevation of systemic blood pressure compared with that in the control group, and cerebral autoregulation was impaired. After a 1-hour study, the specific gravity of the cerebral tissue in the treated group significantly decreased; electron microscopic studies at that time revealed brain edema. It is suggested that depletion of brain noradrenaline levels causes a disturbance in cerebral microvascular tone and renders the cerebral blood vessels more vulnerable to hypertension. | |
| Authors | H Kobayashi, M Hayashi, H Kawano, Y Handa, M Kabuto, H Ide (Affiliation: Department of Neurosurgery, Fukui Medical School, Matsuoka, Japan.) |
|---|---|
| Journal | Journal of neurosurgery (J Neurosurg) Vol. 75 Issue 6 Pg. 906-10 (Dec 1991) ISSN: 0022-3085 UNITED STATES |
| PMID | 1941119 (Publication Type: Journal Article) |
American Institute for Hyperhidrosis claims to cure anxiety and palpitations with ETS
Palpitations caused by anxiety can be significantly reduced.
Migraine occurrence and trembling of the hands may improve.
(They also claim, that Copensatory Hyperhidorsis is) "tolerable by most patients and only 5% describe it as troublesome. Some patients say it improves with time."
http://www.handsweat.com/sideeff.html
Question: what is the scientific definition for troublesome? Some patients say it improves with time? Surely that is not a statement worthy of a website such as this.
There has been no clinical evaluation of the severity of the so called CS to this day. Surgeons who perform the surgery and profit from it claim it to be close to insignificant..that even improves with time. Other sources will state 90% of severe CS, and 25% disabling CS. Surely it can not be just a question of semantics when you have a 25% chance of being disabled after an elective surgery!
Doctors are unable to support their claims about the positive outcomes of the surgery. There has been no controlled trial to support their positive advertising, and it is left solely to the discretion of the surgeon to admit or deny the incidence and severity of the side-effects.
Migraine occurrence and trembling of the hands may improve.
(They also claim, that Copensatory Hyperhidorsis is) "tolerable by most patients and only 5% describe it as troublesome. Some patients say it improves with time."
http://www.handsweat.com/sideeff.html
Question: what is the scientific definition for troublesome? Some patients say it improves with time? Surely that is not a statement worthy of a website such as this.
There has been no clinical evaluation of the severity of the so called CS to this day. Surgeons who perform the surgery and profit from it claim it to be close to insignificant..that even improves with time. Other sources will state 90% of severe CS, and 25% disabling CS. Surely it can not be just a question of semantics when you have a 25% chance of being disabled after an elective surgery!
Doctors are unable to support their claims about the positive outcomes of the surgery. There has been no controlled trial to support their positive advertising, and it is left solely to the discretion of the surgeon to admit or deny the incidence and severity of the side-effects.
Sympathectomy leads to a decrease in noradrenaline levels in the cerebral cortex
Chemical Sympathectomy leads to a decrease in noradrenaline levels measured in the cerebral cortex. (Onesti at al. 1989)
brain levels of norepinephrine were reduced significantly
EFFECT OF 6-HYDROXYDOPAMINE ON BRAIN NOREPINEPHRINE AND DOPAMINE: EVIDENCE FOR SELECTIVE DEGENERATION OF CATECHOLAMINE NEURONS
1 Departments of Psychiatry and Pharmacology and the Child Development Institute, University of North Carolina School of Medicine, Chapel Hill, North Carolina
After the intracisternal administration of 6-hydroxydopamine, brain levels of norepinephrine were reduced significantly with or without pargyline pretreatment. Depletion of dopamine in the central nervous system was found to be enhanced markedly by pargyline administration at higher dose levels of 6-hydroxydopamine. Brain serotonin concentrations were not altered. The effects of 6-hydroxydopamine were long-lasting with the depletion of brain amines persisting at 78 days. After norepinephrine-H3 intracisternally to animals treated with 6-hydroxydopamine, labeled norepinephrine uptake was diminished with a corresponding reduction of deaminated catechols and a marked increased in methylated amines. Tyrosine hydroxylase activity was found to be reduced in brainstem, caudate nucleus and whole brain in 6-hydroxydopamine-treated animals. Conversion of tyrosine-H3 to labeled norepinephrine and dopamine was also markedly diminished. The results support the view that 6-hydroxydopamine produces a "central sympathectomy" when introduced into cerebrospinal fluid.
Journal of Pharmacology And Experimental Therapeutics, Vol. 174, Issue 3, 413-420, 1970Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics
6-OHDA depressed hypothalamic norepinephrine levels in both sexes
6-OHDA depressed hypothalamic norepinephrine levels in both sexes.
Copyright © 1973 S. Karger AG, Basel
Copyright © 1973 S. Karger AG, Basel
Sex-Dependent Increase in Pineal Hydroxyindole-O-Methyl Transferase Activity After a Single Intraventricular Injection of 6-Hydroxydopamine to Newborn Rats
M.T. Hyyppä, D.P. Cardinali, R.J. Wurtman
Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
Neuroendocrinology 1973;11:274-283 (DOI: 10.1159/000122140)
sympathectomy impairing adrenergic transmission
The chronic bilateral cervical superior sympathectomy could provoke norepinephrine depletion in the small granular vesicles of the sympathetic terminals, impairing adrenergic transmission; this would then eliminate the constrictor sympathetic effect13. Our study is in agreement with published data where pharmacological or anatomical exclusion of the sympathetic activity prevented vasospasm24.
Antônio Tadeu de Souza FaleirosI; Francisco Humberto de Abreu MaffeiII; Luiz Antonio de Lima ResendeIII
IServices of Neurosurgery, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil
IIVascular Surgery, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil
IIINeurology, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, SP, Brazil
marked changes in brain NE following sympathectomy
Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats
EM Johnson , E Cantor and JR Douglas
The administration of guanethidine to newborn rats has been shown by morphological criteria to destroy sympathetic neurons. Newborn rats were injected with guanethidine (50-100 mg/kg/day for 20 days). Upon maturation (at 10 weeks old), the degree of destruction of the sympathetic nervous system (sympathectomy) was assessed. Marked decreases (80-98%) in the norepinephrine concentration in several tissues (heart, spleen, intestine, mesentery, kidney, uterus, vas deferens) were observed in the guanethidine-treated rats when compared to saline-treated controls. No changes were observed in the epinephrine concentration in the adrenals or in the norepinephrine levels in whole brain. Analysis of brain areas showed no change in the norepinephrine levels in brain stem and cerebrum and a small (18%) decrease in the cerebellum. Stimulation of the sympathetic vasomotor outflow in the pithed rat preparation produced almost no response in guanethidine- treated animals. Periarterial nerve stimulation of the isolated perfused kidney preparation also produced essentially no response in guanethidine-treated animals. Isolated intestinal preparations from guanethidine-treated animals responded to nerve stimulation with contractions rather than relaxation as seen in preparations from control animals. Isolated vas deferens preparations responded normally to nerve stimulation despite a 95% decrease in tissue norepinephrine concentration. These data indicate that administration of guanethidine to newborn rats produces a more complete peripheral sympathectomy, especially of the vasculature, than immunosympathectomy or neonatal administration of 6-hydroxydopamine and does so with no significant effect on central noradrenergic neurons.
Volume 193, Issue 2, pp. 503-512, 05/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics
the adrenergic system in regulation of the metabolism of the retina
Stefan M. Pojda1 
and Ryszard Brus2
| (1) | Department of Ophthalmology, Silesian Academy of Medicine, Francuska str. 20/24, 40-027 Katowice, Poland |
| (2) | Department of Pharmacology, Silesian Academy of Medicine, Zabrze 8, Poland |
Received: 16 April 1976
Summary Male Wistar rats were injected intraventricularly with two doses of 250 mcg of 6-hydroxydopamine (6-OHDA) in two consecutive days. Two weeks later the oxygen uptake, anaerobic glycolysis and lactic acid dehydrogenase (LDH) activity in the retina were determined. The decrease of oxygen uptake (–28 %), anaerobic glycolysis (–31 %) and LDH activity (–12 %) in rats treated with 6-OHDA in comparison to control animals was found. The possible role of the adrenergic system in regulation of the metabolism of the retina is discussed.
Heightened emotions cause experiences to crystallize into lasting and vivid memories
Emotional memory.(NEUROSCIENCE)(effect of Norepinephrine to memory)(Brief article)
Where were you on Sept. 11, 20017 Or when the shuttle Challenger exploded in 19867 Heightened emotions cause experiences to crystallize into lasting and vivid memories. This boost in memory formation is due in part to the stress hormone norepinephrine, but scientists haven't understood how the hormone causes this effect.
Now researchers have uncovered molecular changes triggered by norepinephrine that help nerve cells form new memories.
A team led by Roberto Malinow of Cold Spring Harbor Laboratory in New York traced the hormone's effects to a receptor molecule called glutamate receptor 1 (G1uR1) on the surfaces of nerve cells. Through G1uR1 and similar receptors, ... http://www.highbeam.com/doc/1G1-170372501.html
brain norepinephrine turnover, and memory and the need for Power
David C. McClelland1 , J. Anderson Maddocks1 and Dan P. McAdams1, 2
| (1) | Department of Psychology and Social Relations, Harvard University, 33 Kirkland Street, 02138 Cambridge, Massachusetts |
| (2) | Present address: Loyola University of Chicago, USA |
Abstract Subjects were classified according to whether they were high or low in the need for Power and high or low in gain in 3-methoxy-4-hydroxyphenylglycol (MHPG), a putative index of brain norepinephrine (NE) turnover, after engaging in some tasks that involved memory for story content. Subjects who were high inn Power and in the index of brain NE turnover showed better recall of power-related facts than subjects low on both these characteristics, confirming an earlier finding, which suggests that the need for Power is subserved by a noradrenergic reward system in the brain.
The need for power, brain norepinephrine turnover, and memory
| Journal | Motivation and Emotion |
| Publisher | Springer Netherlands |
| ISSN | 0146-7239 (Print) 1573-6644 (Online) |
| Issue | Volume 9, Number 1 / March, 1985 |
| DOI | 10.1007/BF00991546 |
| Pages | 1-10 |
| Subject Collection | Behavioral Science |
| SpringerLink Date | Monday, January 10, 2005 |
Norepinephrine
Doze said the adrenergic system — one of the essential neurochemical systems in the brain — synthesizes and controls the release of the neurotransmitter norepinephrine (also known as noradrenalin).
Norepinephrine works in both the central and peripheral nervous systems. It’s responsible for many critical functions, but in this context, its key functions in the central nervous system include sleep, emotions, learning, and memory.Probing the deepest levels of brain chemistry to uncover clues to memory loss
By Juan Miguel Pedraza
Emotion enhances learning via norepinephrine regulation
A neurotransmitter involved in emotional arousal enhances learning by phosphorylating glutamate receptors.
Do you remember the song that was playing during your first kiss? Both positive and negative emotions influence learning and memory but researchers have not determined the mechanism. Now Hu et al. report that the neurotransmitter norepinephrine regulates glutamate receptor trafficking in a recent article in Cell.
Axon terminals containing norepinephrine synapse in the hippocampus and amygdala, which are important in emotional memory. In the hippocampus, norepinephrine reduces the threshold for long-term potentiation (LTP), which is thought to be a substrate of memory. Norepinephrine acts at 
-adrenergic receptors, where it activates cAMP-dependent protein kinase (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII). These kinases phosphorylate serines 845 and 831, respectively, in the AMPA glutamate receptor type 1 (GluR1). The authors proposed that norepinephrine regulates learning by phosphorylating AMPA receptors.
Hu, H. et al. Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 131, 160–173 (2007). | Article | PubMed |
Emotional intelligence
Neuroscience Gateway (October 2007) |
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.
Received 9 June 2005;
Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral β-adrenergic receptors
Received 9 June 2005;
revised 17 August 2005;
accepted 29 August 2005.
Available online 17 October 2005.
arousal related hormone affects memory processing
A significant number of animal and human studies demonstrate that memories for new experiences are encoded more effectively under environmental or laboratory conditions which elevate peripheral concentrations of the hormone epinephrine and in turn, induce emotional arousal. Although this phenomenon has been replicated across several learning paradigms, understanding of how this arousal related hormone affects memory processing remains obscure because epinephrine does not freely enter into the central circulation to produce any direct effects on the brain. This study examined whether epinephrine’s actions on the CNS may be mediated by the initial activation of peripheral vagal fibers that project to the brain.
Received 9 June 2005;
Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral β-adrenergic receptors
Received 9 June 2005;
revised 17 August 2005;
accepted 29 August 2005.
Available online 17 October 2005.
The role of norepinephrine in spatial reference and spatial working memory
The role of norepinephrine in spatial reference and 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.
Michael J. Gertner, University of Pennsylvania
Steven A. Thomas, University of Pennsylvania
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.
Michael J. Gertner, University of Pennsylvania
Steven A. Thomas, University of Pennsylvania
Norepinephrine Important In Retrieving Memories
Norepinephrine Important In Retrieving Memories
Source: U. Of Pennsylvania Medical Center
Date: 2 April 2004
In addition, beta-blockers, which are used to treat heart failure and hypertension (among other ailments) block the same norepinephrine receptors important for memory retrieval. Therefore, when treating heart disease, the use of beta blockers that do not cross into the brain may help to avoid memory-related side effects, suggest the researchers.
The findings of this research appear in the April 2 issue of Cell.
Source: U. Of Pennsylvania Medical Center
Date: 2 April 2004
In addition, beta-blockers, which are used to treat heart failure and hypertension (among other ailments) block the same norepinephrine receptors important for memory retrieval. Therefore, when treating heart disease, the use of beta blockers that do not cross into the brain may help to avoid memory-related side effects, suggest the researchers.
The findings of this research appear in the April 2 issue of Cell.
Causes of Orthostatic Hypotension
Causes of Orthostatic Hypotension:
Neurologic (involving autonomic dysfunction)
Surgical sympathectomy
http://www.merck.com/mmpe/sec07/ch069/ch069d.html
Neurologic (involving autonomic dysfunction)
Surgical sympathectomy
http://www.merck.com/mmpe/sec07/ch069/ch069d.html
NE levels and Posttraumatic Stress Disorder
CSF Norepinephrine Concentrations in Posttraumatic Stress Disorder
Thomas D. Geracioti, Jr., M.D.
Dewleen G. Baker, M.D.
Nosakhare N. Ekhator, M.S.
Scott A. West, M.D.
Kelly K. Hill, M.D.
Ann B. Bruce, M.D.
Dennis Schmidt, Ph.D.
Barbara Rounds-Kugler, R.N.
Rachel Yehuda, Ph.D.
Paul E. Keck, Jr., M.D.
John W. Kasckow, M.D., Ph.D.
Objective: Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD.
Method: CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under base-
line (unstressed) conditions. Severity of the patients’ PTSD symptoms was assessed with the Clinician-Administered PTSD Scale.
Results: CSF norepinephrine concentrations were significantly higher in the men
with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and
positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms.
Conclusions: These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.
(Am J Psychiatry 2001; 158:1227–1230)
Thomas D. Geracioti, Jr., M.D.
Dewleen G. Baker, M.D.
Nosakhare N. Ekhator, M.S.
Scott A. West, M.D.
Kelly K. Hill, M.D.
Ann B. Bruce, M.D.
Dennis Schmidt, Ph.D.
Barbara Rounds-Kugler, R.N.
Rachel Yehuda, Ph.D.
Paul E. Keck, Jr., M.D.
John W. Kasckow, M.D., Ph.D.
Objective: Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD.
Method: CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under base-
line (unstressed) conditions. Severity of the patients’ PTSD symptoms was assessed with the Clinician-Administered PTSD Scale.
Results: CSF norepinephrine concentrations were significantly higher in the men
with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and
positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms.
Conclusions: These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.
(Am J Psychiatry 2001; 158:1227–1230)
Alterations in T and B cell proliferation and differentiation in vitro following chemical sympathectomy
Madden, K.S., Moynihan, J.A., Brenner, G.J., Felten, S.Y., Felten, D.L. and Livnat, S. (1994b).:Sympathetic nervous system modulation of the immune system. III. Alterations in T and B cell proliferation and differentiation in vitro following chemical sympathectomy. J. Neuroimmunol. 49: 77-87.
reduced antibody responses to T-dependent antigens
It has been exhaustively demonstrated that the regions in which lymphocytes T cells reside, and through which they recirculate, receive direct sympathetic neural input. Therefore, the immune system can be considered “hard-wired” to the brain. Chemical sympathectomy of adult mice resulted in reduced antibody responses to T-dependent antigens. The interaction between sympathetic NA nerve fibers and cells of the immune system has been shown through the distribution of tyrosine hydrolase (TH+) nerve fibers among lymphocytes and macrophages in lymphoid organs, the expression of adrenoceptors on cells of the immune system, and the immunomodulatory effects of NA. In old rats, a conspicuous decline in NA innervation and NA contents is observed in the splenic white pulp as well as in the cell bodies in superior celiac-mesenteric ganglia that provide preganglionic sympathetic innervation to the spleen (Arnason, 1993; Carlson, Fox et al., 1997; Madden. Felten et al., 1994a; Roszman and Carlson, 1991). Paralleling these alterations in sympathetic NA neuronal activity is an age-related loss of T cell mediated immune responses, including reduced T cell proliferation and IL-2 production by antigen- and mitogen-stimulated lymphocytes. Treatment of these rats with drugs inducing noradrenergic regeneration and re-innervation reverted the rats’ immune abnormalities (Tang, Shankar et al., 1999; Thyaga-Rajan, Madden et al., 1999). Noradrenergic innervation of the spleen is responsible for a significant increase of gamma-interferon, IL-2 and tumor necrosis factor alpha, the three Th-1 cytokines, and a lowering of IL-4, IL-5 and IL-10 (TH-2 cytokines) production (Carlson, Fox et al., 1997; Madden, Moynihan et al., 1994b; Spengler, Allen et al., 1990). Other evidence showed that elevated plasma NA concentrations increased the level of Th-1 cytokines (Kappel, Poulsen et al., 1998; Ross, Williams et al., 1987). These and other findings demonstrate that the noradrenergic innervation of bone marrow is functionally dynamic and is responsive to central activation. Furthermore, these results lend credence to the premise that neural mechanisms participate in regulating lymphopoietic cellular events.
VOL. 31, NOS. 5 & 6, 2000 JOURNAL OF MEDICINE
JOURNAL OF MEDICINE
Copyright © 2000 by
PJD Publications Limited
The hepatic sympathetic nerve
Mortality in sympathectomised mice was significantly higher than that in sham operated mice following administration of Jo-2. This result was also supported by apoptosis data in which sympathectomised livers exhibited a significant elevation in the number of apoptotic hepatocytes and caspase-3 activity after Jo-2 treatment compared with sham operated livers. Moreover, pretreatment with norepinephrine dose dependently inhibited the hepatic sympathectomy induced increase in mortality after Jo-2 injection. Antiapoptotic protein levels of FLICE inhibitory protein, Bcl-xL, and Bcl-2 in the liver were significantly lower in sympathectomised mice at one and two hours following Jo-2 treatment than in sham operated animals. In addition, interleukin 6 supplementation dose dependently suppressed the hepatic sympathectomy induced increase in mortality after Jo-2 treatment.
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
The hepatic sympathetic nerve plays a critical role in preventing Fas induced liver injury in mice
Y Chida1, N Sudo1, A Takaki2, C Kubo1 1 Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
2 Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Dr Y Chida
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
The sympathoadrenal system is one of the major pathways mediating physiological responses
The sympathoadrenal system is one of the major pathways mediating physiological responses in 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.
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.
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