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

direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias

Anesthesiol Res Pract. 2013;2013:413985. doi: 10.1155/2013/413985. Epub 2013 Oct 23.

Supraventricular arrhythmias after thoracotomy: is there a role for autonomic imbalance?

Vretzakis G1, Simeoforidou M, Stamoulis K, Bareka M.

Author information

Abstract

Supraventricular arrhythmias are common rhythm disturbances following pulmonary surgery. The overall incidence varies between 3.2% and 30% in the literature, while atrial fibrillation is the most common form. These arrhythmias usually have an uneventful clinical course and revert to normal sinus rhythm, usually before patent's discharge from hospital. Their importance lies in the immediate hemodynamic consequences, the potential for systemic embolization and the consequent long-term need for prophylactic drug administration, and the increased cost of hospitalization. Their incidence is probably related to the magnitude of the performed operative procedure, occurring more frequently after pneumonectomy than after lobectomy. Investigators believe that surgical factors (irritation of the atria per se or on the ground of chronic inflammation of aged atria), direct injury to the anatomic structure of the autonomic nervous system in the thoracic cavity, and postthoracotomy pain may contribute independently or in association with each other to the development of these arrhythmias. This review discusses currently available information about the potential mechanisms and risk factors for these rhythm disturbances. The discussion is in particular focused on the role of postoperative pain and its relation to the autonomic imbalance, in an attempt to avoid or minimize discomfort with proper analgesia utilisation.

http://www.ncbi.nlm.nih.gov/pubmed/24235971

"Since changes in old age show some similarities with those following chronic sympathectomy"

"For the tracheobronchial tree. surgical (sympathectomy) and chemical (with 6-hydroxydopamine or reserpine) interventions lead to histological disappearance of the NA and NPY." (p.435)

" Prejunctional supersensitivity to norepinephrine after sympathectomy or cocaine treatment." (p. 410)

"Following chronic sympathectomy, substance P expression in presumptive sensory nerves....and NPY-expression in parasympathetic nerves ...to autonomically innervated tissues have both been shown to increase... Experiments using NGF and anti-NGF antibodies (Kessler et al., 1983) have suggested that competition between sympathetic and sensory fibers for target-derived growth factors could explain these apparently compensatory interactions,..." (p. 33)

"Since changes in old age show some similarities with those following chronic sympathectomy, it is tempting to consider whether alterations in one group of nerves in tissues with multiple innervations trigger reciprocal changes in other populations of nerves, perhaps through the mechanism of competition for common, target-produced growth factors. The nature of these changes is such that they could be nonadaptive and even destabilizing of cardiovascular homeostasis. (p. 34) 

Impairment of sympathetic and neural function has been claimed in cholesterol-fed animals (Panek et al., 1985). It has also been suggested that surgical sympathectomy may be useful in controlling atherosclerosis in certain arterial beds (Lichter et al., 1987). Defective cholinergic arteriolar vasodilation has been claimed in atherosclerotic rabbits (Yamamoto et al., 1988) and, in our laboratory, we have recently shown impairment of response to perivascular nerves supplying the mesenteric, hepatic, and ear arteries of Watanabe heritable hyperlipidemic rabbits (Burnstock et al., 1991). 
   Loss of adrenergic innervation has been reported in alcoholism (Low et al., 1975), amyloidosis (Rubenstein et al., 1983), orthostatic hypotension (Bannister et al., 1981), and subarachnoid haemorrhage (Hara and Kobayashi, 1988). Recent evidence shows that there is also a loss of noradrenergic innervation of blood vessels supplying malignant, as compared to benign, human intracranial tumours (Crockard et al., 1987). (p. 14)  

Vascular Innervation and Receptor Mechanisms: New    Perspectives 

Rolf Uddman

Academic Press, 2 Dec 2012 - Medical - 498 pages

sympathectomy leads to fluctuation of vasoconstriction alternated with vasodilation in an unstable fashion. Following sympathectomy the involved extremity shows regional hyper - and hypothermia

"To quote Nashold, referring to sympathectomy, "Ill- advised surgery may tend to magnify the entire symptom complex"(38). Sympathectomy is aimed at achieving vasodilation. The neurovascular instability (vacillation and instability of vasoconstrictive function), leads to fluctuation of vasoconstriction alternated with vasodilation in an unstable fashion (39). Following sympathectomy the involved extremity shows regional hyper - and hypothermia in contrast, the blood flow and skin temperature on the non- sympathectomized side are significantly lower after exposure to a cold environment (39). This phenomenon may explain the reason for spread of CRPS. In the first four weeks after sympathectomy, the Laser Doppler flow study shows an increased of blood flow and hyperthermia in the extremity (40). Then, after four weeks, the skin temperature and vascular perfusion slowly decrease and a high amplitude vasomotor constriction develops reversing any beneficial effect of surgery (39). According to Bonica , "about a dozen patients with reflex sympathetic dystrophy (RSD) in whom I have carried out preoperative diagnostic sympathetic block with complete pain relief, sympathectomy produced either partial or no relief (40)"

Chronic Pain: 

 Reflex Sympathetic Dystrophy : Prevention and Management

Hooshang Hooshmand

CRC PressINC, 1993 - Medical - 202 pages

Despite the simplicity and rapidity of the procedure, some patients experience intense, in some cases persistent, postoperative pain

Jornal Brasileiro de Pneumologia - The incidence of residual pneumothorax after video-assisted sympathectomy with and without pleural drainage and its effect on postoperative pain:

"Anteroposterior chest X-ray in the orthostatic position, while inhaling, was absolutely normal in 18 patients (32.1%), and residual pneumothorax was detected in 17 patients (30.4%). When the patients were separated into two groups (those who had received drainage and those who had not), 25.9% (7 patients) and 34.4% (10 patients), respectively, presented residual pneumothorax, with no difference between the two groups (p = 0.48) (Figure 1).

The additional alterations were laminar atelectasis and emphysema of the subcutaneous cellular tissue.

Chest X-rays in the orthostatic position, while exhaling, revealed residual pneumothorax in 39.3% (22 patients) and was absolutely normal in 25% (14 patients). On the same X-rays, when patients were analyzed separately, residual pneumothorax was seen in 33.3% of the patients who had received drainage (9 patients) and in 44.8% (13 patients) of those who had not, with no difference between the two groups (p = 0.37) (Figure 1).

The low-dose computed tomography scans of the chest detected residual pneumothorax in 76.8% (43 patients). In the patients submitted to postoperative drainage, this rate was 70.3% (19 patients), compared with 82.7% (24 patients) in those without pleural drainage, with no difference between the two groups (p = 0.27) (Figure 1). Therefore, the overall rate of occult pneumothorax (only visible through tomography), revealed on anteroposterior X-rays was 35.7% (20 patients): 48.2% while patients were inhaling and 41.1% while patients were exhaling. The VAS score in the PACU ranged from 0 to 10, with a mean of 2.16 ± 0.35.

Regarding characteristics, 44.6% of the patients reported chest pain upon breathing and 32.1% reported retrosternal pain. The same evaluation performed in the infirmary, during the immediate postoperative period, ranged from 0 to 10, with a mean of 3.75 ± 0.30, being 69.6% of chest pain upon breathing and 78.6% of retrosternal pain. On postoperative day 7, according to VAS, pain ranged from 0 to 10, with a mean of 2.05 ± 0.31; regarding characteristics, it was continuous in 32.1% of the cases, and retrosternal in 26.8%. On postoperative day 28, pain ranged from 0 to 3, with a mean of 0.17 ± 0.08, 7.1% of mechanical rhythm and 5.4% upper posterior."

Jornal Brasileiro de Pneumologia

Print version ISSN 1806-3713

J. bras. pneumol. vol.34 no.3 São Paulo Mar. 2008

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1806-37132008000300003&lng=en&nrm=iso&tlng=en

"sympathicotomy may cause a temporary impairment of the caudal-to-rostral hierarchy of thermoregulatory control and changes in microcirculation"

Patients with palmar hyperhidrosis have been reported to have a much
more complex dysfunction of autonomic nervous system, involving compensatory high parasympathetic activity as well as sympathetic overactivity (13, 14), suggesting that sympathicotomy initially induces a sympathovagal imbalance with a parasympathetic predominance, and that this is restored on a long-term basis (14). Therefore, thoracic sympathicotomy may cause a temporary impairment of the caudal-to-rostral hierarchy of thermoregulatory control and changes in microcirculation.
The reduction
of finger skin temperature on the non-denervated side may be due to either a decrease in the cross-
inhibitory effect or the abnormal control of the inhibitory fibers by the sudomotor center (6).
Vasoconstrictor neurons have been found to be largely under the inhibitory control of various afferent
input systems from the body surface, whereas sudomotor neurons are predominantly under excitatory
control (15). The basic neuronal network for this reciprocal organization is probably located in the spinal level (15). Therefore, the reduction in the contralateral skin temperature may be explained by cross-inhibitory control of various afferent in the spinal cord.
In particular, our study showed that, following bilateral T3 sympathicotomy, the skin temperatures on
the hands increased whereas the skin temperatures on the feet decreased. These findings suggest a
cross-inhibitory control between the upper and lower extremities. However, the pattern of skin
temperature reduction on the feet differed from that on the contralateral hand. The skin temperature on
the feet did not decrease after right T3 sympathicotomy but decreased significantly after bilateral T3
sympathicotomy.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722005/

Other neurological pathways (pathways of the nervous system) involving the cerebral cortex (an area of the brain that processes complex information and regulates voluntary movement) and hypothalamus (a hormone-producing gland in the brain) are also thought to play a role in hyperhidrosis

"Sweat is secreted by sweat glands, normally as a thermoregulatory response. No changes to the sweat glands (e.g. increased quantity or size) are observed in individuals with focal hyperhidrosis, so the condition is hypothesised to arise due to overactivity of the sympathetic nervous system (the section of the nervous system that regulates involuntary muscle movements), which sends the signals to the sweat glands to trigger sweating. Other neurological pathways (pathways of the nervous system) involving the cerebral cortex (an area of the brain that processes complex information and regulates voluntary movement) and hypothalamus (a hormone-producing gland in the brain) are also thought to play a role in hyperhidrosis, as is the parasympathetic nervous system."
https://archive.today/xyNQ2
or
http://sydneynorthneurology.com.au/focal-hyperhidrosis/

functional abnormality detected in the small airway of patients who underwent bilateral dorsal sympathectomy to treat primary hyperhidrosis is still present 3 years after surgery

The main observation of our study was that the functional abnormality detected in the small airway of patients who underwent bilateral dorsal sympathectomy to treat primary hyperhidrosis is still present 3 years after surgery, although the patients remain clinically asymptomatic.

Studies to date evaluate alterations in lung function at 1, 3, and 6 months after sympathectomy. Only 1 recent study provides data 1 year after surgery. Ponce González et al¹⁰ studied a group of 37 patients who underwent forced spirometry before surgery, and at 3 months and 1 year after surgery. They observed a decrease in FVC, FEV₁, and FEF_25%-75% at 3 months, although FVC returned to baseline values at 12 months, whereas FEV₁ and FEF_25%-75% remained significantly low (-2.8% and -11.2%, respectively). These findings are consistent with ours, and corroborate the persistence of minimal bronchial obstruction 3 years after surgery. This appears to be associated with the influence of the sympathetic nervous system on bronchomotor tone.

As previously mentioned, the airway is innervated mainly by the parasympathetic nervous system. Sympathetic innervation, although scant, indirectly affects motor tone and could have caused the mild residual obstructive pattern after surgery. Despite the doubtful role of the sympathetic nervous system in the lung, a series of physiologic studies show the effect of sympathetic nervous activity after bilateral dorsal sympathectomy.^11,12 The first was by Noppen and Vincken⁴, who compared the results of lung function studies (spirometry, diffusion, and lung volumes using plethysmography) in 7 patients before dorsal sympathectomy performed using VATS, at 6 weeks, and at 6 months (previous studies had been performed using invasive techniques [thoracotomy]). A statistically significant decrease was observed in FEV₁, FEF_25%-75%, and total lung capacity 6 weeks after surgery. At 6 months, the authors again evaluated the 35 patients and found that total lung capacity had returned to normal values, whereas FEF_25%-75% remained low. They attributed the permanent decrease in FEF_25%-75% to the sympathetic denervation produced by surgery, and stressed that, in patients with primary hyperhidrosis, bronchomotor tone is influenced by the sympathetic nervous system. This contrasts with the common opinion that motor tone in the airway is not affected by this system. Both the study by Ponce González et al,¹⁰ who evaluated their patients at 1 year, and our study, in which we evaluated patients at 3 years, show that persistence of the decrease in FEF_25%-75% over time is related more to sympatholysis of the ganglia than to VATS.

http://www.archbronconeumol.org/en/bilateral-dorsal-sympathectomy-for-the/articulo/13147806/

Effect of ganglion blockade on cerebrospinal fluid norepinephrine

Prevention of ganglion blockade-induced hypotension using phenylephrine did not prevent the decrease in CSF NE caused by trimethaphan, and when phenylephrine was discontinued, the resulting hypotension was not associated with increases in CSF NE. The similar decreases in plasma NE and CSF NE during ganglionic blockade, and the abolition of reflexive increases in CSF NE during hypotension in ganglion-blocked subjects, cast doubt on the hypothesis that CSF NE indicates central noradrenergic tone and are consistent instead with at least partial derivation of CSF NE from postganglionic sympathetic nerve endings.

 http://www.mendeley.com/research/effect-of-ganglion-blockade-on-cerebrospinal-fluid-norepinephrine/

"sympathectomy, although having varying results, does seem to increase the severity of autoimmune disorders"

Allostasis - a state of imbalance responsible for Autoimmune disorders

In general, enhancing the sympathetic tone decreases both T0-cell and NK cell functions but not the proliferation of splenic B cells (Dowdell and Whitacre, 2000). In contrast, chemical sympathectomy, although having varying results, does seem to increase the severity of autoimmune disorders (Dowdell and Whitacre, 2000)
As far as metabolism, catecholamines promote mobilization of fuel stores at time of stress and act synergistically with glucocorticoids to increased glycogenolysis, gluconeogenesis, and lipolysis but exert opposing effects of protein catabolism, as noted earlier. One important aspect is regulation of body temperature (Goldsttein and Eisenhofer, 2000) Epinephrine levels are also positively related to serum levels of HDL cholesterol and negatively related to triglycerines. However, perturbing the balance of activity of various mediators or metabolism and body weight regulation can lead to well-known metabolic disorders such as type 2 diabetes and obesity.

At the same time, increased sympathetic activitation and nerephinephrine release is elevated in hypertensive individuals and also higher levels of insulin, and there are indications that insulin further increases sympathetic activity in a vicious cycle (Arauz-Pacheco et al.,1996)

As a result of either local production, cytokines often enter the the circultion and can be detected in plasma samples. Sleep deprivation and psychological stress, such as public speaking, are reported to elevate inflammatory cytokine level in blood (Altemus et al., 2001) Circulting levels of a number of inflammatory cytokines are elevated in relation to viral and other infections and contirbute to the feeling of being sick, as well as sleepiness, wiht both direct and indirect effects on the central nervous system (Arkins et al., 2000; Obal and Kueger, 2000)

Inflammatory autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, reflect an allostatic state that consists of at least three principal causes: genetic risk factors, (...) factors that contribute to the development of tolerance of self-antigens (...) and the hormonal mikieu that regulates adaptive immunes responses (Dowdell and Whitacre, 2000)

Allostasis, homeostasis and the costs of physiological adaptation

By Jay SchulkinCambridge University Press, 2004

Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change. This can be carried out by means of alteration in HPA axishormones, the autonomic nervous system, cytokines, or a number of other systems, and is generally adaptive in the short term ^[1]

"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"



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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

"Sympathectomy is a destructive procedure that interrupts the sympathetic nervous system"

Cervico-thoracic or lumbar sympathectomy for neuropathic pain | Cochrane Summaries: "Sympathectomy is a destructive procedure that interrupts the sympathetic nervous system. Chemical sympathectomies use alcohol or phenol injections to destroy sympathetic nervous tissue (the so-called "sympathetic chain" of nerve ganglia). Surgical ablation can be performed by open removal or electrocoagulation (destruction of tissue with high-frequency electrical current) of the sympathetic chain, or by minimally invasive procedures using thermal or laser interruption. Nerve regeneration commonly occurs following both surgical or chemical ablation, but may take longer with surgical ablation.

This systematic review found only one small study (20 participants) of good methodological quality, which reported no significant difference between surgical and chemical sympathectomy for relieving neuropathic pain. Potentially serious complications of sympathectomy are well documented in the literature, and one (neuralgia) occurred in this study.

The practice of sympathectomy for treating neuropathic pain is based on very weak evidence. Furthermore, complications of the procedure may be significant."



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Cervico-thoracic or lumbar sympathectomy | Cochrane Summaries

Cervico-thoracic or lumbar sympathectomy for neuropathic pain | Cochrane Summaries: "Sympathectomy is a destructive procedure that interrupts the sympathetic nervous system. Chemical sympathectomies use alcohol or phenol injections to destroy sympathetic nervous tissue (the so-called "sympathetic chain" of nerve ganglia). Surgical ablation can be performed by open removal or electrocoagulation (destruction of tissue with high-frequency electrical current) of the sympathetic chain, or by minimally invasive procedures using thermal or laser interruption. Nerve regeneration commonly occurs following both surgical or chemical ablation, but may take longer with surgical ablation.

This systematic review found only one small study (20 participants) of good methodological quality, which reported no significant difference between surgical and chemical sympathectomy for relieving neuropathic pain. Potentially serious complications of sympathectomy are well documented in the literature, and one (neuralgia) occurred in this study.

The practice of sympathectomy for treating neuropathic pain is based on very weak evidence. Furthermore, complications of the procedure may be significant."



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the clinical results of both surgical and neurolityc sympathectomy are uncertain

Blood diverted from muscle to skin after sympathectomy

However, the clinical results of both surgical and neurolityc sympathectomy are uncertain. Indeed these procedures lead to a redistribution of the blood flow in the lower limbs from the muscle to the skin, with a concomitant fall of the regional resistance, mainly in undamaged vessels. The blood flow will be diverted into this part of the vascular tree, so that a "stealing" of the blood flow may occur.

Vito A. Peduto, Giancarlo Boero, Antonio Marchi, Riccardo Tani

Bilateral extensive skin necrosis of the lower limbs following prolonged epidural blockade

Anaesthesia 1976; 31: 1068-75.

Stellate ganglion block - a form of chemical sympathectomy - 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

Permanent pain following sympathectomy

The mean inpatient pain scores were significantly higher in the biportal group (1.2±0.6) than that in the uniportal group (0.8±0.5, P=0.025). For the first three weeks after operation, four out of 20 (20%) patients in the uniportal group constantly suffered from mild or moderate residual pain while eight out of 25 (32%) cases in the biportal group (P=0.366). Among them, two cases in the uniportal group and five cases in the biportal group need to take analgesics.
Chinese Medical Journal, 2009, Vol. 122 No. 13 : 1525-1528

CARDIOVASCULAR CHANGES POST SYMPATHECTOMY

Short- and Long-term Effects

Pulse rates taken at rest and after effort were significantly
lower than those taken after operation, and the blood pressure
response to exercise was blunted. ECG tracings showed a sig-
nificant change in the electrical frontal plane axis and shortening
of the QTc interval.

Tel-Hashomer, and Tel Aviv University Sackler Medical
School, Tel Aviv, Israel, and the National Heart,
Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland

The so called 'compensatory sweating' is NOT compensatory - BMJ Best Practice

"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&pid=S1806-37132008001100013&lng=en&nrm=iso&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^*

http://bestpractice.bmj.com/best-practice/search.html?searchableText=Hyperhidrosis&aliasHandle=guidelines&languageCode=en
https://archive.today/wrNOi
https://archive.today/0UXdW

significant adverse effects on cardiopulmonary physiology

Because of technologic advances and improved postoperative recovery, endoscopic surgery has become the technique of choice for many thoracic surgical procedures^6and 25; however, endoscopic visualization of intrathoracic structures requires retraction or collapse of the ipsilateral lung, which can have significant adverse effects on cardiopulmonary physiology. These cardiopulmonary changes can be further affected by the pathophysiologic changes associated with the disease process requiring the surgical procedure.

Because acute changes in cardiopulmonary function can compromise patient safety severely, a clear understanding of the dynamic interaction between the anesthetic–surgical technique and patient physiology is essential. This article discusses the effect of thoracoscopic surgery and the impact of various anesthetic interventions on cardiovascular and pulmonary physiology. In addition, some recommendations for “damage control” are made.
Anesthesiology Clinics of North America
Volume 19, Issue 1, 1 March 2001, Pages 141-152

Postsympathectomy pain of such severity that parenteral narcotics afforded no relief

Fifty-six consecutive patients who subsequently underwent ninety-six lumbar sympathectomies were studied prospectively with regard to the development of postoperative pain. Pain after operation was observed in thirty-four extremities by twenty-five of the patients (35 per cent). It began abruptly an average of twelve days after operation and was often accentuated nocturnally. The pain was almost always described as a deep, dull ache and persisted two to three weeks before spontaneously remitting. Postsympathectomy pain of such severity that parenteral narcotics afforded no relief developed in two of these fifty-six patients and in nine additional patients. Treatment with carbamazepine produced dramatic reduction in the intensity of pain in seven of these nine patients within twenty-four hours after the institution of therapy. Two patients were given intravenous diphenylhydantoin and both experienced immediate relief of pain. The mechanisms of the syndrome and of the action of these drugs are uncertain.

http://www.sciencedirect.com/science/article/pii/0002961074902384

Sympathectomy decreased CD4+ T-cells in lymph nodes - Sympathetic denervation leads to loss of an important regulatory mechanism in immune system physiology

Sympathectomy decreased CD4+ T-cells in lymph nodes.
Alterations in lymphocyte activity does not always correlate with changes in the proportions of T- or B-lymphocyte subsets. Sympathetic denervation leads to loss of an important regulatory mechanism in immune system physiology. This is apparently site specific in that both lymph node and spleen T-cell proliferative responses are reduced.
Article by Dr. Brian A. Smith
http://home.earthlink.net/~doctorsmith/hivandchiro.htm

Degeneration patterns of postganglionic fibers following sympathectomy

In the muscle nerves the first signs of an axonal degeneration of the sympathetic fibers can be recognized 4 days after surgery. The signs of axonal degeneration are most striking about 8 days p.o. They have more or less disappeared another week later. The reactions of the Schwann cells also start on the fourth day but outlast the degenerative processes by some 8 days. Thus the degenerative and reactive processes in the reg precede those in the muscle nerves by 2 days early after surgery and by 6 days 3 weeks later. Seven weeks after surgery, fragments of folded basement lamella and Remak bundles with condensed cytoplasm and numerous flat processes are persisting signs of the degeneration.
K. H. Andres, M. von Düring, W. Jänig and R. F. Schmidt
Anatomy and Embryology
Springer Berlin / Heidelberg
Volume 172, Number 2 / August, 1985
http://www.springerlink.com/content/m21m2612n2147011/

Pain in the form of intercostal neuralgia with dysesthesia at the site of trocar insertion is rarely documented but more frequent than generally recognized

Pain in the form of intercostal neuralgia with dysesthesia at the site of trocar insertion is rarely documented but more frequent than generally recognized. Many centres perform short-stay surgery that may lead to underestimation of pain results. In most series pain resolves within months, but Walles and colleagues could detect a persistence for years (Walles et al., 2008).

http://www.intechopen.com/books/topics-in-thoracic-surgery/surgical-management-of-primary-upper-limb-hyperhidrosis-a-review

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 mechanisms by which sympathectomy leads to increased local bone loss is unknown

In vivo effects of surgical sympathectomy on intra... [Am J Otol. 1996] - PubMed - NCBI: "Am J Otol. 1996 Mar;17(2):343-6.

In vivo effects of surgical sympathectomy on intramembranous bone resorption.
Sherman BE1, Chole RA.
Author information
1Department of Otolaryngology--Head and Neck Surgery, School of Medicine, University of California, Davis, USA.
Abstract
Bone modeling and remodeling are highly regulated processes in the mammalian skeleton. The exact mechanism by which bone can be modeled at a local site with little or no effect at adjacent anatomic sites is unknown. Disruption of the control of modeling within the temporal bone may lead to various bone disease such as otosclerosis, osteogenesis imperfecta, Paget's disease of bone, fibrous dysplasia, or the erosion of bone associated with chronic otitis media. One possible mechanism for such delicate control may be related to the ubiquitous and rich sympathetic innervation of all periosteal surfaces. Previous studies have indicated that regional sympathectomy leads to qualitative alterations in localized bone modeling and remodeling. In this study, unilateral cervical sympathectomy resulted in significant increases in osteoclast surface and osteoclast number within the ipsilateral bulla of experimental animals. The mechanisms by which sympathectomy leads to increased local bone loss is unknown. Potential mechanisms include disinhibition of resorption, secondary to the elimination of periosteal sympathetics, as well as indirect vascular effects."

the sympathetic fibers passing through the T2-3 ganglia play an important role in the elaboration or modulation of autonomic function elsewhere

The data indicate that the sympathetic fibers passing through the T2-3 ganglia play an important role in the elaboration or modulation of autonomic function elsewhere.

Journal of the Autonomic Nervous System
Volume 8, Issue 1, May 1983, Pages 33-43

Because of the anaesthetic implications and possible surgical complications, many surgeons are reluctant to perform transthoracic sympathectomy

Hypoxaemia is of a major concern during thorascopic sympathectomy. However, the pathophysiology of hypoxaemia and consequent decrease in SpO2 differs between the two anaesthetic techniques.

The normal physiological response to massive atelectasis is an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction) with re-routing of blood to well ventilated lung zones and consequent improvement in PaO2. HOWEVER, DURING ENDOBRONCHIAL ANAESTHESIA FOR THORACIC SYMPATHECTOMY THERE IS AN APPARENT FAILURE OF THIS COMPENSATORY MECHANISM. When more then 70% of the lung is atelectatic, compensation by hypoxic pulmonary vasoconstriction appears ineffective.

During carbon dioxide insufflation using endobronchial intubation, Hartrey and colleagues reported a decrease in systolic arterial pressure of >20mm Hg in 21% of patients. Similarly we have reported sudden hypotension and bradycardia after injudicious carbon dioxide insufflation.

Although extremely rare, sudden cardiac arrest has been reported after left T2-3 sympathetic nerve transection. While the exact pathophysiology of this occurence is unclear, it is postulated that before complete transection of the sympathetic trunk, continuous sympathetic stimulation to the stellate ganglions results in a reduction in the ventricular finrillation threshold, arrhythmia and cosequent cardiac arrest.
In an iteresting study of the delayed cardiac effects of T2-$ symtpathectomy, Drott and colleagues demonstrated significantly reduced heart rate at rest, and during both exercise and the recovery phase of exercise. Changes is the electrical axis and shortening of the QT interval have also been reported.

Irrespective of the technique used the reported incidence of postoperative pneumpthorax is variable, occuring in 2-15% of cases.
In a study by Gothberg, Drott and Claes, postoperative chest x-ray after 1274 procedures, in 602 patients demonstrated that a small apical pneumothroax was a usual occurence.

Conclusion: Because of the anaesthetic implications and possible surgical complications, many surgeons are reluctant to perform transthoracic sympathectomy.

British Journal of Anaesthesia 1997; 79: 113-119
B. Fredman, D. Olsfanger and R. Jedeikin

ETS considered psychiatric surgery - says Dr Nagy

"ETS (sympathectomy) can alter many bodily functions, including sweating , heart rate , heart stroke volume , blood pressure , thyroid , baroreflex , lung volume , pupil dilation, skin temperature, goose bumps and other aspects of the autonomic nervous system . It can diminish the body's physical reaction to exercise and/or strong emotion, and thus is considered psychiatric surgery. In rare cases sexual function or digestion may be modified as well."
http://www.lvhyperhidrosis.com/treatment.html

The second thoracic sympathetic ganglion was most commonly located (50%) in the second intercostal space

anatomic variations of the T2 nerve root

6 (9.1%) sides showed a single large ganglion formed by the stellate and the second thoracic sympathetic ganglia. The second thoracic sympathetic ganglion was most commonly located (50%) in the second intercostal space. Conclusion: The anatomic variations of the intrathoracic nerve of Kuntz and the second thoracic sympathetic ganglion were characterized in human cadavers.

Journal of thoracic and cardiovascular surgery Y. 2002, vol. 123, No. 3, pages 498-501 [bibl. : 14 ref.

http://www.refdoc.fr/Detailnotice?idarticle=9466218

"Please note, due to the complications of the ETS procedure and the few people who need it, ETS is NOT offered anymore at The Whiteley Clinic."

"Please note, due to the complications of the ETS procedure and the few people who need it, ETS is NOT offered anymore at The Whiteley Clinic."

http://www.sweating.co.uk/treatments_ETS-endoscopic-transthoracic-sympathectomy.htm
or archived page:

https://archive.today/PCmQf#selection-409.0-409.141

He had several websites promoting the procedure and used the media to advertise ETS:
http://www.sweating.co.uk/press-mark-whiteley.htm
or archived page:
https://archive.today/GKztq

Endoscopic Thoracic Sympathectomy (ETS) is major surgery with a high possibility of permanent damage and irreversible side effects

http://www.hyperhidrosisuk.org/treatment-options.html

Neurogenic and non-neurogenic inflammation in the rat paw following chemical sympathectomy

Neurogenic and non-neurogenic inflammation in t... [Neuroscience. 1991] - PubMed - NCBI: "Neuroscience. 1991;45(3):761-5.



Neurogenic and non-neurogenic inflammation in the rat paw following chemical sympathectomy.
Donnerer J1, Amann R, Lembeck F.
Author information
Abstract
Rats with chemical sympathectomy, induced either at neonatal age (long-term sympathectomy) or in adult animals (short-term sympathectomy) by guanethidine or by 6-hydroxydopamine, were used to determine the contribution of sympathetic noradrenergic fibres to afferent neuron-mediated responses and to non-neurogenic inflammation in the rat. Following long-term sympathectomy with 6-hydroxydopamine there was a 66% depletion of noradrenaline in the paw skin. This was accompanied by a 20-53% increase in the levels of sensory neuropeptides in the paw skin and sciatic nerve. A hypersensitivity towards heat stimuli was observed in the tail immersion test. "

Drawbacks of thoracoscopic sympathectomy | The BMJ

Drawbacks of thoracoscopic sympathectomy | The BMJ: "BMJ 2005; 330 doi: http://dx.doi.org/10.1136/bmj.330.7500.1127 (Published 12 May 2005)
Cite this as: BMJ 2005;330:1127
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Drawbacks of thoracoscopic sympathectomy

Side effects after thoracoscopic sympathectomy have been discussed
widely in Taiwan society in the past few months. Lots of people in Taiwan
suffer from hyperhidrosis palmaris. Thoracoscopic sympathectomy is covered
by our National Health Insurance, and yet patient billing for this
operation does not exceed US$ 60. This is why this operation is so popular
here (1). However, patients with serious compensatory sweating must change
clothes several times a day (some complain they change as often as 10
times a day), resulting in a serious impact on work and social
interaction. Patients suffering from such serious side effects in Taiwan
have formed a support group based on an Internet discussion forum to
request the government to take this problem seriously
(http://home.pchome.com.tw/family/vivi12175/). Since October 2004, The
Department of Health Executive, Yuan, Taiwan, has prohibited surgeons from
performing this operation on patients under 20 years of age. To our
knowledge, this type of Internet-based support group also exists in
England (http://www.noetsuk.com/), Sweden
(http://home.swipnet.se/sympatiska/index3.htm), Australia (http://www.ets-
sideeffects.netfirms.com/), Spain
(http://www.terra.es/personal8/hiperhidrosis/principal.htm) and Japan
(http://www.geocities.jp/etscontroversialop/index.html). Thoracoscopic
sympathectomy is a relatively safe and simple procedure, however, the side
effects are potentially devastating. All surgeons who do the operation and
individuals preparing to undergo this treatment should know this well.
1.Lin TS, Wang NP, Huang LC. Pitfalls and complication avoidance
associated with transthoracic endoscopic sympathectomy for primary
hyperhidrosis (analysis of 2200 cases). Int J Surg Investig 2001; 2: 377-
85."

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

“In no other area than Sympathetic Surgery, disagreement, conflicting opinion, different definitions and misleading interpretations of the data exist"

8th ISSS Symposium New York, 2009: 

“In no other area than Sympathetic Surgery, disagreement, conflicting opinion, different definitions and misleading interpretations of the data exist. Mainly regarding surgical indications, the level and extent of the procedure and results evaluation”.

ATS Expert Consensus for the Surgical Treatment of Hyperhidrosis powerpoint presentation  – October 6, 2012, XVI Congreso Boliviana de Cirugia Cardiaca, Toracica y Vascular, Santa Cruz de la Sierra, Bolivia.

http://cirugiadetorax.org/2012/10/09/vats-sympathectomy-for-hyperhidrosis-dr-jose-ribas-de-milanez-de-campos/

or:

https://archive.today/Q047q

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

significant change after sympathectomy: QT dispersion was significantly reduced 1 month after surgery and the dispersion was further diminished 2 years later

The HRV analysis showed a significant change of indices reflecting sympatho-vagal balance indicating significantly reduced sympathetic (LF) and increased vagal (HF, rMSSD) tone. These changes still persisted after 2 years. Global HRV increased over time with significant elevation of SDANN after 2 years. QT dispersion was significantly reduced 1 month after surgery and the dispersion was further diminished 2 years later.

http://www.sciencedirect.com/science/article/pii/S0167527399001011

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

Functional and organic vascular wall changes after sympathectomy and partial nerve damage

Langenbecks  

Arch  

Klin  

Chir  

Ver  

Dtsch  

Z  

Chir.  

1959;;291:217-31. 

In the setting of sympathectomy, interference with any of the effectors evokes immediate, precipitous declines in blood pressure

"From the finding that removal of the sympathetic nerves did not affect blood pressure much, Cannon inferred that the sympathetic nervous system did not contribute to blood pressure in intact, undisturbed organism. In the 1980s, however, several reports showed  that sympathectomy compensatorily activates other effectors, such as the renin-angiotensin-aldosterone system, the vasopressin system, and the adrenal medulla, and compensatory activation of these effectors maintains blood pressure at approximately normal levels. In the setting of sympathectomy, interference with any of the effectors evokes immediate, precipitous declines in blood pressure. Because Cannon was so firmly convinced of the functional unity of the sympathoadrenal system, which would be activated only in emergencies, he never considered adequately the possibility that the sympathetic nervous system might indeed contribute to levels of blood pressure and other monitored variables under resting conditions." Adrenaline and the Inner World:  An Introduction to Scientific Integrative Medicine

David S. Goldstein

JHU Press, 01/04/2008 - Medical - 328 pages

"patient information must include the long-term substantial risk for severe CS and regret of the procedure"

http://www.ncbi.nlm.nih.gov/pubmed/22191130

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