dysregulation of the immune system after sympathectomy (Haug and Heyeraas, 2005

dr.sagepub.com/content/85/6/488.full.pdf

The altered pattern of the response suggests that the nitric oxide-dependent portion may be accelerated in sympathectomized limbs

J Appl Physiol. 2002 Feb;92(2):685-90.

Depression of Endothelial Nitric Oxide Synthase but Increased Expression of Endothelin-1 Immunoreactivity in Rat Thoracic Aortic Endothelium Associated with long-term Sympathectomy

Circulation Research. 1996;79:317-323

After unilateral sympathectomy the incidence of calcified arteries on the side of operation was significantly higher than that on the contralateral side

Medial arterial calcification is frequently seen in diabetic patients with severe diabetic neuropathy. Sixty patients (19 diabetic and 41 non-diabetic) were examined radiologically for typical Monckeberg's sclerosis of feet arteries 6-8 years after uni- or bilateral lumbar sympathectomy. Fifty-five out of 60 patients (92%) revealed medial calcification. This calcification was observed in both feet of 93% of patients, who had undergone bilateral operation. After unilateral sympathectomy the incidence of calcified arteries on the side of operation was significantly higher than that on the contralateral side (88% versus 18%, p less than 0.01). Although diabetic patients showed longer
stretches of calcification than non-diabetic subjects, the difference was not significant in terms of incidence and length. Of 20 patients who had no evidence of calcinosis pre-operatively, 11 developed medial calcification after unilateral operation exclusively on the side of sympathectomy. In seven patients calcinosis was detected in both feet after bilateral operation. In conclusion, sympathetic denervation is one of the causes of Monckeberg's sclerosis regardless of diabetes mellitus.
PMID: 6873514 [PubMed - indexed for MEDLINE]
Diabetologia. 1983 May;24(5):347-50.

in the media of FAs hypercholesterolemia induces changes similar to those observed in sympathectomized rabbits in non-pathological conditions

In a previous study, we showed that after sympathectomy, the femoral (FA) but not the basilar (BA) artery from non-pathological rabbits manifests migration of adventitial fibroblasts (FBs) into the media and loss of medial smooth muscle cells (SMCs). The aim of the present study was to verify whether similar behaviour of arteries occurred in the pathological context of atherosclerosis.
Our results show that in the media of FAs hypercholesterolemia induces changes similar to those observed in sympathectomized rabbits in non-pathological conditions, i.e., migration of adventitial FBs to the media and loss of medial SMCs. These latter changes, which can be ascribed to pathological events, were accentuated after sympathectomy in the hypercholesterolemic rabbits. The present study reveals that pathological events, including migration and phenotypic modulation of vascular FBs and loss of SMCs, may be under the influence of sympathetic nerves.
Acta Histochemica; Jul2008, Vol. 110 Issue 4, p302-313, 12p

sympathectomy results in an increased collagen content in the vascular wall, suggesting a stiffening of the vessel wall

From animal experiments, it is known that long-term sympathectomy results in an increased collagen content in the vascular wall, suggesting a stiffening of the vessel wall (9). Giannattasio et al.

MEDICINE & SCIENCE IN SPORTS & EXERCISE®
Copyright © 2005 by the American College of Sports Medicine
DOI: 10.1249/01.mss.0000174890.13395.e7

cervical sympathectomy resulted in a moderate and short decrease in milk secretion

Unilateral cervical sympathectomy resulted in a moderate and short decrease in milk secretion, the average amount of milk given by operated animals 10 days after operation being 76-3% of the initial level. Total cervical sympathectomy (the 2nd operation was performed 1 month later) caused a much greater and more prolonged decrease in milk secretion, 59.7% of the initial level being secreted during the 10 days after operation. A gradual increase in milk secretion was observed after the operation and this increase was more gradual after total sympathectomy than after partial sympathectomy. Denervation of the thyroid and parathyroids did not decrease milk secretion. Section of the pituitary stalk in 6 goats, which included complete section (2 goats), complete section with scar tissue at the site of section and considerable damage to the median eminence of the tuber einereum (1 goat) and incomplete section (3 goats) was performed. Milk ejection disappeared completely for 7-11 days in the goats with complete section and remained defective for some weeks after, but was still effective in those where the infundibular stem and part of the glandular portion of the pituitary stalk was still intact. Milk secretion was 28.9% of the initial level in the goats with complete section and 12.9% in the goat with the scar tissue whereas it was 40.5 and 55.7% in the incompletely sectioned and control operated goats. (See also D.S.A. 21 [3081].) D.E.E.
http://www.cabdirect.org/abstracts/19600402546.html;jsessionid=A943A1F56D5D120B419B65425A893BB0

sympathectomy induces several biochemical changes in skeletal muscle

It is concluded that sympathectomy induces several biochemical changes in skeletal muscle which constitute a change and increase in fast myosin light chain synthesis and a corresponding fibre type transformation.
Received 24 August 1987; accepted 26 October 1987

Clinical Physiology and Functional Imaging

"We have previously reported functional and histological studies in five beagle dogs with unilateral lumbar sympathectomy. Three months later, fatiguability in the gracilis muscles was increased on the denervated sides, and this was associated with an increase in the relative distribution of FT fibres. Biochemical studies now show that these changes were associated with an increase in cytosolic protein without change in DNA content; this is consistent with an increase in cell size. There was a reduction in the proportion of slow myosin light chain isoforms from 50 +/- 7 to 34 +/- 6%. Noradrenaline levels were increased on the denervated sides but this may reflect greater vascularity. Calcium content did not correlate with fibre type but there was a positive relation with both noradrenaline content (r = 0.73; P less than 0.05) and DNA content (r = 0.84; P less than 0.05). It is concluded that sympathectomy induces several biochemical changes in skeletal muscle which constitute a change and increase in fast myosin light chain synthesis and a corresponding fibre type transformation."
Journal: Clinical physiology (Oxford, England) (Clin Physiol), published in ENGLAND.
Reference: 1988-Apr; vol 8 (issue 2) : pp 181-91
Dates: Created 1988/06/08; Completed 1988/06/08; Revised 2004/11/17;
PMID: 3359751, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sympathectomy is another animal.

Sympathectomy. This is a radical, now-controversial approach to blocking pain, and it includes extremely high risks for additional tissue damage and spread of RSD. (p.40)

Sympathectomy also potentially precludes future new treatments from working. (p.41)

A recent review article by (Johns Hopkins Hospital anesthesiologist and medical school professor) Srinivasa Raja covering all previous articles on sympathectomy showed that 10 percent of sympathectomies done for various reasons have complications. The complication rate for sympathectomy done to treat neuropathic (i.e., RSD) pain is 30 percent. A lot of these people can have a return of pain, and if they do, you can no longer do a sympathetic block to get rid of it. Then you have got these people in terrible pain that you cannot treat. And so, in my book, surgical sympathectomy is out. (p.81)

Positive Options for Reflex Sympathetic Dystrophy (RSD):

Elena Juris

6 Reviews

Hunter House, 2004

cerebral edema following CO2 insufflation during sympathectomy

Death after thoracoscopic sympathectomy has been reported, secondary to cerebral edema, when CO2 insufflation has been employed. Another patient in this series sustained severe neurological dysfunction, secondary to cerebral edema. The development of cerebral edema after thoracoscopic sympathectomy is attributable to gas insufflation, which is not required and should be avoided. Major vascular injury during thoracoscopic sympathectomy has also been reported, and this complication should be completely avoidable. Chylothorax after sympathectomy has also been described and is related to division of accessory ducts rather than injury to the thoracic duct.
The most common complications of sympathectomy are related to manipulation of the autonomic nervous system.

Injury to the stellate ganglion is caused by mechanical or thermal damage to T1 during dissection. In order to prevent this injury, precise identification of ribs 1-4 is required prior to dissection of the sympathetic ganglion at T2; no dissection is performed above this level. Furthermore, excessive nerve traction is avoided during dissection. Finally, the use of bipolar cautery or ultrasonic dissection will prevent current diffusion to the stellate ganglion.
Neuralgia along the ulnar aspect of the upper limb may occur after sympathectomy, which usually resolves within 6 weeks. (p.250)

Complications in cardiothoracic surgery: avoidance and treatment

By Alex G. Little

Wiley-Blackwell, 2004 - Medical - 454 pages

sympathectomy per se may sensitize peripheral nociceptors and lead to neuralgia

Interestingly, while is used for the treatment of some chronic pain conditions, sympathectomy per se may sensitize peripheral nociceptors to circulating norephinephrine, and this sensitization may lead to post-sympathectomy neuralgia. (p.287)

Peripheral Receptor Targets for Analgesia: Novel Approaches to Pain Management

By Brian E. Cairns
John Wiley and Sons, 2009 - Medical

Patient describes waking up "feeling very detached" after sympathectomy...

http://www.dailymail.co.u...gery-cured-blushing.html

most of the existing literature is geared towards assessing only the effectiveness of the surgical sympathectomy

Given the fact that most of the existing literature is geared towards a) assessing only the effectiveness of the surgical sympathectomy procedures, and b) publishing only studies with positive results, adverse effects and complications are not systematically reported but rather as a secondary outcome. It seems, therefore, highly likely that the complications as reported here, are truly underestimated.

The study indicates that surgical sympathectomy, irrespective of operative approach and indication, may be associated with many and potentially serious complications.

Are We Paying a High Price for Surgical Sympathectomy? A Systematic Literature Review of Late Complications

http://www.jpain.org/article/S1526-5900%2800%2944124-6/abstract

a significant impairment of the heart rate to workload relationship was consistently observed following sympathectomy

Several reports also demonstrate significantly lower heart rate increases during exercise in subjects who have undergone bilateral ISS [9–12] compared to pre-surgical levels. In spite of this high occurrence, recent reviews on the usual collateral effects of thoracic sympathectomy still do not include these possible cardiac consequences [6].
The aim of the present prospective study was to confirm that a significant impairment of the heart rate to workload relationship was consistently observed following unilateral and/or bilateral surgery.
Eur J Cardiothorac Surg 2001;20:1095-1100
http://ejcts.ctsnetjourna...i/content/full/20/6/1095

All possible side effects should be dealt with and written informed consent required

Thoracoscopic sympathicotomy by electrocautery is an irreversible procedure. Thus the indications must be meticulously considered before the final decision to operate is taken by both the surgeon and the patient. All possible side effects should be dealt with and written informed consent required.

http://www3.interscience....ct?CRETRY=1&SRETRY=0

Published Online: 2 Dec 2003

Copyright © 2002 Taylor and Francis Ltd

All possible side effects should be dealt with and written informed consent required

Thoracoscopic sympathicotomy by electrocautery is an irreversible procedure. Thus the indications must be meticulously considered before the final decision to operate is taken by both the surgeon and the patient. All possible side effects should be dealt with and written informed consent required.

http://www3.interscience....ct?CRETRY=1&SRETRY=0

Published Online: 2 Dec 2003

Copyright © 2002 Taylor and Francis Ltd

slowing of the heart rate usually occurs on the second to fourth day after sympathectomy

The rate fell to a level between 40 and 6o per minute, the maximal slowing usually occurring on the second to fourth day after operation. Consistent slowing of the rate was not observed after a unilateral thoracic sympathectomy of either side. While there was some recovery from the maximum brady-
cardia with the passage of time in most patients, relatively slow resting cardiac rates and failure of tachycardia to develop with postural hypotension or exercise persisted in all patients.



Skoog's12 work has shown that there are marked differences in the number and precise location of the accessory ganglion cells in the cervical region in different patients and on the two sides in the same patient.

Even when a single midthoracic paravertebral ganglion is left in place in an otherwise total sympathectomy the thoracic dermatome supplied by the ganglion appears for several days or weeks to be sympathectomized also. Then, sweating begins to appear, and it increases gradually in amount until the skin of that dermatome may be dripping. This phenomenon more than any other meets the
objection of those who maintain that if residual pathways do exist, the evidence of their presence should be manifest immediately after operation.
Annals of Surgery, 1949 October
Volume 130 Number 4

Reported success stories of sympathectomy are "prone to bias and have significant methodological problems"

Australian Review of ETS surgery - 2001
The four case series were not critically appraised because they are prone to bias and have significant methodological problems. These studies represent level IV evidence according to the NHMRC criteria and one should not draw firm conclusions from their findings.

To date, the benefits or side effects associated with endoscopic thoracic sympathectomy for treating facial blushing have not been properly evaluated and reported.

Further research using a well-designed controlled trial is warranted to assess the efficacy of endoscopic thoracic sympathectomy for treating facial blushing.

Centre for Clinical Effectiveness - Monash

sympathectomy must somehow quiet the contralateral spread of spinal cord hyperexcitability underlying mirror-image pain

Blocking sympathetic function, whether by surgical sympathectomy, systemic phentolamine, or systemic guanethidine, relieves partial nerve injury-induced neuropathic pain in laboratory animal models as well as humans (8, 35, 146, 239, 278). Indeed, sympathectomy does not just relieve pathological pain in the body region ipsilateral to the CRPS-initiating event; rather, it also relieves pain arising from anatomically impossible mirror-image sites, that is, the identical body region contralateral to the initiating event (278). Thus sympathectomy must somehow quiet the contralateral spread of spinal cord hyperexcitability underlying mirror-image pain. 

Alterations in sympathetic fibers rapidly follow peripheral nerve injury. This occurs as sprouting of sympathetic fibers, creating aberrant communication pathways from the new sympathetic terminals to sensory neurons (35). Sympathetic sprouting has been documented in the region of peripheral terminal fields of sensory neurons (262), at the site of nerve trauma (57), and within the dorsal root ganglia (DRG) containing cell bodies of sensory neurons (248, 343). Each of these sites develops spontaneous activity and sensitivity for catecholamines and sympathetic activation (8, 53). 

The clearest evidence that immune activation participates in sympathetic sprouting comes from studies of the DRG. DRG cells receive signals that peripheral nerve injury has occurred via retrograde axonal transport from the trauma site. These retrogradely transported signals trigger sympathetic nerve sprouting into DRG (205, 308). As a result of nerve damage-induced retrogradely transported signals, glial cells within the DRG (called satellite cells) proliferate (248) and become activated (343); macrophages are recruited to the DRG as well (63, 176). In turn, the activated satellite glial cells (and, presumably, the macrophages) release proinflammatory cytokines and a variety of growth factors into the extracellular fluid of the DRG (206, 246 –248, 258, 277, 308, 358). These substances stimulate and direct the growth of sympathetic fibers, which form basket-like terminals around the satellite cells that, in turn, surround neuronal cell bodies (247, 248, 343). 

Until recently, the sympathetic sprouting, rather than the glial (satellite cell) activation, has attracted the attention of pain researchers. The satellite cells were ignored as they were thought to be irrelevant to the creation of exaggerated pain states. However, it may be speculated that the satellite cells, rather than the sympathetic sprouts, have the most impact on pain.

Physiol Rev • VOL 82 • OCTOBER 2002 • www.prv.org

Beyond Neurons: Evidence That Immune and Glial Cells 

Contribute to Pathological Pain States 

LINDA R. WATKINS AND STEVEN F. MAIER 

Department of Psychology and the Center for Neuroscience, 

University of Colorado at Boulder, Boulder, Colorado 

Chronic pain can occur after peripheral nerve injury, infection, or inflammation

Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, 

proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability.

Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.

Physiol Rev   82: 981–1011, 2002; 10.1152/physrev.00011.2002.