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

www.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, but Not Short-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

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: )

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

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

Collagen types I and III mRNA were decreased respectively by 53% and 22% after sympathectomy

In the present study, we tested the hypothesis of the indirect (via the sympathetic nervous system (SNS)) and direct (via AT1 receptors) contributions of Angiotensin II (Ang II) on the synthesis of collagen types I and III in the left ventricle (LV) in vivo. Sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA and protein synthesis of collagen types I and III were examined by Q-RT-PCR and immunoblotting in the LV.

Collagen types I and III mRNA were decreased respectively by 53% and 22% after sympathectomy and only collagen type I mRNA was increased by 52% after AT1 receptor blockade. mRNA was not changed for collagen type I but was decreased by 25% for collagen type III after double treatment. Only collagen protein type III was decreased after sympathectomy by 12%, but collagen proteins were increased respectively for types I and III by 145% and 52% after AT1 receptor blockade and by 45% and 60% after double treatment. Deducted interpretations from our experimental approach suggest that Ang II stimulates indirectly (via SNS) and inhibits directly (via AT1 receptors) the collagen type I at transcriptional and protein levels. For collagen type III, it stimulates indirectly the transcription and inhibited directly the protein level. Therefore, the Ang II regulates collagen synthesis differently through indirect and direct pathways.

http://www.autonomicneuroscience.com/article/S1566-0702(09)00416-0/abstract

we conclude that the sympathetic nervous system influences the metabolic activity of the aorta

The effect of chemical sympathectomy with 6-hydroxydopamine (6-OH-DA) on collagen formation in the aortic wall was investigated in rabbits and rats. Eight weeks after 6-OH-DA treatment of rabbits, there was a significant increase an collagen content in aortas and histologic changes in the elastic elements within the media. The possibility of a direct effect of 6-OH-DA on connective tissue formation was investigated in a subsequent experiment in rats. The rates of collagen synthesis and prolyl hydroxylase activity (PHA) were determined in aortas and in the fibrotic granuloma around subcutaneously implanted polyvinylalcohol sponges. Rates of collagen synthesis and PHA were significantly increased in the aortas of 6-OH-DA treated rats, but not in fibrotic granuloma, confirming the changes seen in the aorta of rabbits and suggesting that 6-OH-DA does not directly affect collagen synthesis. We conclude that the sympathetic nervous system influences the metabolic activity of the aorta. Our data indicate that when the aortic wall is deprived of adrenergic nervous stimulation, changes occur which resemble those seen in natural aging of the aorta. It is plausible to assume that such a metabolic derangement in the vessel wall will make these vessels more vulnerable to additional stresses.

Experimental and Molecular Pathology
Volume 28, Issue 3, June 1978, Pages 279-289

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.ctsnetjournals.org/cgi/content/full/20/6/1095

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. 

may be relevant to the pathogenesis of human dysautonomias

1. Systemic injection of monoclonal antibodies to neural acetylcholinesterase in adult rats caused a syndrome with permanent, complement-mediated destruction of presynaptic fibers in sympathetic ganglia and adrenal medulla. Ptosis, hypotension, bradycardia, and postural syncope ensued. In sympathetic ganglia, acetylcholinesterase activity disappeared from neuropil but not from nerve cell bodies. Choline acetyltransferase activity and ultrastructurally defined synapses were also lost. Electrical stimulation of presynaptic fibers to the superior cervical ganglion ceased to evoke end-organ responses. On the other hand, direct ganglionic stimulation remained effective, and the postganglionic adrenergic system appeared intact. Motor performance and the choline acetyltransferase content of skeletal muscle were preserved, as was parasympathetic (vagal) function. This model of selective cholinergic autoimmunity represents another tool for autonomic physiology and may be relevant to the pathogenesis of human dysautonomias.
2. http://www.jstor.org/pss/2356466

mechanism of pulmonary edema following sympathectomy

Unilateral pulmonary edema is unusual in presentation and is mainly seen in the re-expansion phase after pneumothorax, systemic-to-pulmonary shunt, parenchymal lung disease, and unilateral sympathectomy. The mechanisms of unilateral pulmonary edema include an increase in capillary blood flow, reduced surfactant, rapid re-expansion of a collapsed lung, and disruption of venular post-capillary sphincter function after sympathectomy.^1–3

http://onlinelibrary.wiley.com/doi/10.1111/j.1527-5299.2005.03861.x/full