diabetic autonomic neuropathy is due to a lesion of the sympathetic nerve supply to the skin

"We conclude that the diabetic anhidrotic syndrome, a form of diabetic autonomic neuropathy, is due to a lesion of the sympathetic nerve supply to the skin."

Diabetologia

Volume 22, Number 2, 96-99, DOI: 10.1007/BF00254836

Sympathectomy IS a (surgically caused) lesion of the sympathetic nerve supply to the skin (and other structures)

Effects of Sympathectomy on the mean decrease in HBF (Hypothalamic blood flow)

Intrahypothalamic injection of 0.1 mug of tyramine caused a mean decrease in HBF of 15.6 ml/100 g per min (P less than 0.001). This effect of intrahypothalamic injection of tyramine was abolished by bilateral cervical sympathectomy but not by chemical sympathectomy of the upper brainstem. These results support the idea that local CBF, at least in the hypothalamus, is mediated by two distinct pathways. The first consists of the sympathetic nerves which arise in the cervical ganglia, and which activate intrahypothalamic alpha-receptors to cause constriction. The second is an entirely intracerebral noradrenergic pathway which stimulates beta-receptors to cause vasodilation.
http://circres.ahajournals.org/cgi/content/abstract/circresaha;38/3/140
Circulation Research, Vol 38, 140-145, Copyright © 1976 by American Heart Association

Cutaneous vasodilator responses induced by activation of hypothalamic heat loss mechanisms are completely abolished by sympathectomy

http://www3.interscience.wiley.com/journal/121531565/abstract

sympathectomy significantly increased the ratio of patients exhibiting a positive response to methacholine

Of 46 patients who had a negative result for methacholine challenge preoperatively, 12 (26%) became positive after surgery. In terms of the level of sympathectomy, T3 sympathectomy significantly increased the ratio of patients exhibiting a positive response to methacholine (from 19% to 34%, respectively) (p < 0.005).
Conclusions. Thoracic sympathectomy can adversely affect lung function early after surgery, although the clinical significance is uncertain. It may also exert an influence on the development of bronchial hyperresponsiveness, especially when performed at the T3 level.
Journal of Asthma, 46:276–279, 2009

Evidence: sympathectomy created imbalance of autonomic activity and functional changes of the intrathoracic organs

Surgical thoracic sympathectomy such as ESD or heart transplantation can result in an imbalance between the sympathetic and parasympathetic activities and result in functional changes
in the intrathoracic organs.
Therefore, the procedures affecting sympathetic nerve functions, such as epidural anesthesia, ESD, and heart transplantation, may cause an imbalance between sympathetic and parasympa-
thetic activities (1, 6, 16, 17). Recently, it has been reported that ESD results in functional changes of the intrathoracic organs.


In conclusion, our study demonstrated that ESD adversely affected lung function early after surgery and the BHR was affected by an imbalance of autonomic activity created by bilateral ESD in patients with primary focal hyperhidrosis.
Journal of Asthma, 46:276–279, 2009

THE SYMPATHETIC NERVOUS SYSTEM AS A HOMEOSTATIC MECHANISM

The responses of intact rats to cold-exposure (4°C) include vasoconstriction, piloerection, shivering, adrenocorticotrophin (ACTH) hypersecretion and increased mobilization of free fatty acids and glucose. Adrenal demedullation prevents the increased mobilization of glucose and decreases survival time. Chemical sympathectomy blocks all of the responses except ACTH hypersecretion. Such animals lose body heat rapidly and die in a few hours. Total adrenalectomy has a similar effect. The damaging actions of chemical sympathectomy are reversed by administration of catecholamines while those of total adrenalectomy are reversed by cortisone. Thus, the sympathetic nervous system appears to be essential for existence at low environmental temperature.

http://jpet.aspetjournals.org/cgi/content/abstract/157/1/103

Pathophysiology of Diarrhea and Malabsorption

Disordered motility

• Post-vagotomy

• Post-sympathectomy

• Diabetic neuropathy

• Hyperthyroidism

• Addison’s disease (adrenal insufficiency)

• Irritable bowel syndrome

Laurence Scott Bailen, M.D.: Diarrhea and Malabsorption
http://ocw.tufts.edu/Content/48/lecturenotes/571075

Response to adrenaline after sympathectomy

None of the hands in this series
exhibited significant change in flow with A1 ,ug/min. With A ,ug/min, however,
eight of the thirteen hands now had 25 % or more vasoconstriction, the mean
for the group being 30 %. With i p,g no less than eight of the ten hands tested
had more than 25 % vasoconstriction.
Thus for the two groups receiving H and i ug adrenaline marked increases
in the mean responses from 11 to 30 % and from 16 to 44 %, respectively, were
observed after sympathectomy. The ratio of postoperative to preoperative
mean responses was about the same for both doses (2-7 and 2-8). The increased
response after sympathectomy is seen (Table 2) to be due especially to changes
in hands 3, 6, 9, 11, 12 and 13, which before operation had minimal constric-
tions but responded with marked reductions in blood flow after sympathectomy.
The altered behaviour of two of these hands is portrayed in Figs. 1 and 2.
Although some of the other seven hands also showed increased vasoconstric-
tion with a given dose of adrenaline after sympathectomy this increase was
less notable.
The paired differences between the hands before and after sympathectomy
are significant at the A .g/min (t = 3-03, P < 0-02), and the i ,ug/min (t = 3-55,
P < 0-01) levels. Of the six hands manifesting notable increases in sensitivity
to adrenaline three were sympathectomized by preganglionic section and three
by ganglionectomy.
J. Physiol. (I955) I29, 53-64
EFFECT OF ADRENALINE AND NORADRENALINE ON
BLOOD VESSELS OF THE HAND BEFORE AND AFTER
SYMPATHECTOMY
BY R. S. DUFF
From the Cardiological Department, St Bartholomew's Hospital and the
Sherrington School of Physiology, St Thomas's Hospital, London

Intraneural activated T cells cause focal breakdown of the blood-nerve barrier

These findings demonstrate that activated T cells cause focal breakdown of the BNB, allowing circulating antimyelin antibody to enter the endoneurium with consequent focal demyelination.
Brain. 1995 Aug;118 ( Pt 4):857-68
Intraneural activated T cells cause focal breakdown of the blood-nerve barrier.

Spies JM, Westland KW, Bonner JG, Pollard JD.
Institute of Clinical Neurosciences, University of Sydney, NSW Australia.

Immune and Glial Cells Contribute to Pathological Pain States

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 cellswithin the DRG (called satellite cells) proliferate and become activated; macrophages are
recruited to the DRG as well. 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.
Physiological Reviews, Vol. 82, No. 4, October 2002, pp. 981-1011; 10.1152/physrev.00011.2002.
Copyright ©2002 by the American Physiological Society

Sympathectomy induces mast cell hyperplasia and chronic inflammation

Mast cell hyperplasia is found in different pathologies such as chronic inflammatory processes, fibrotic disorders, wound healing or neoplastic tissue transformation. The functional significance of the accumulation of mast cells in these processes is largely unknown. It is now established that bone marrow-derived mast cell progenitors circulate in peripheral blood and subsequently migrate into the tissue where they undergo final maturation under the influence of local microenvironmental factors. Cytokines are of particular importance for mast cell recruitment, development, and function.
http://www.ncbi.nlm.nih.gov/pubmed/11919420

Long-term superior cervical sympathectomy induces mast cell hyperplasia and increases histamine and serotonin content in the rat dura mater
Copyright © 1999 IBRO. Published by Elsevier Science Ltd.

Cervical sympathectomy affects adrenocorticotropic hormone and thyroid-stimulating hormone

The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.
http://www.springerlink.com/content/g3333g7752201496/

Received: 26 June 1995 Accepted: 1 March 1996

Journal of Anesthesia

Hyperpigmentation after sympathectomy

Clinical and Experimental Dermatology

Volume 5 Issue 3, Pages 349 - 350
Accepted for publication 4 October 1979

Abnormal suntanning following transthoracic endoscopic sympathectomy Transthoracic endoscopic sympathectomy (TES) has become the method of choice for treating patients with palmar hypcrhidrosis. There are few complications reported with this procedure. A complication not described previously is reported here. Accepted: 25 January 1996

M. S. Whiteley, S. B. Ray-Chaudhuri, Mr R. B. Galland *

British Journal of Surgery Volume 83 Issue 12, Page 1782

Cytokines, immune responses and depression

There is now evidence that major depression is accompanied by significant changes in cell-mediated and humoral immunity, and these changes may be related to the pathophysiology or pathogenesis of that illness (Connor and Leonard [1], Dantzer et al. [2], Kim et al. [3], Licinio and Wong [4]), yet data are inconsistent. Some studies have shown that major depression is associated with dysregulation of immune mediators.
However, conflicting results have also been described (Brambilla and Maggioni [12], Brambilla et al. [13], Carpenter et al. [14], Rothermundt et al. [15]). These changes have been considered in terms of the imbalance between individual pro- and anti-inflammatory cytokines and the T helper 1 (Th1) and T helper 1 (Th2) imbalance in major depression. On the other hand, an enhanced secretion of such proinflammatory cytokines would not only lead to activation of T and B lymphocytes, but also could affect the brain and elicit various symptoms of depression, such as loss of appetite, listlessness, and sleep disturbances (Maes [16]).

Cytokines, stress and depressive illness

Cytokines, signaling molecules of the immune system, have been implicated as a contributing factor for mood disorders such as depression. Several lines of evidence supporting this contention are briefly reviewed and caveats are introduced. Essentially, a relationship between cytokines and depression is based on the findings that: 1) proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor-alpha) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment, 2) cytokines induce neuroendocrine and central neurotransmitter changes reminiscent of those implicated in depression, and these effects are exacerbated by stressors, 3) severe depressive illness is accompanied by signs of immune activation and by elevations of cytokine production or levels, and 4) immunotherapy, using interleukin-2 or interferon-alpha, promotes depressive symptoms that are attenuated by antidepressant treatment. It is argued that cytokine synthesis and release, elicited upon activation of the inflammatory response system, provoke neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Furthermore, such effects are subject to a sensitization effect so that a history of stressful experiences or cytokine activation augment the response to later challenges and hence the evolution of depression.

Anisman H, Merali Z.
Institute of Neurosciences,
Carleton University and Institute of Mental Health Research,
Royal Ottawa Hospital, University of Ottawa, Canada.
hanisman@ccs.Carleton.ca
Ann Med 2003;35(1):2-11

Sympathectomy-induced changes is cytokine production and immune effector function

Lacrimal Gland, Tear Film, and Dry Eye Syndromes 2: Basic Science and Clinical Relevance

By David D. Sullivan, Darlene A. Dartt, Michele A. Meneray

Edition: 2, illustrated

Published by Springer, 1998

ISBN 0306458128, 9780306458125

significantly more cholesterol and total lipids in the aorta after sympathectomy

While the vasomotor effect of the sympathetic nervous system (SNS) on the arterial wall is well recognized, its trophic function is not. It is the aim of these studies to demonstrate this all-important function as it relates to the vascular muscle.

Although the exact mechanism by which sympathetic nerve impulses influence the metabolism of the vessel wall is unknown, effects of sympathectomy can be demonstrated. Several lines of evidence indicate that chronic absence of sympathetic innervation in rabbits increases collagen synthesis and decreases activity of tricarboxylic acid cycle enzymes in the vascular wall. When chemically sympathectomized rabbits were fed a 1% cholesterol dietary supplement for 80 days, the aortas of these rabbits contained significantly more cholesterol and total lipids than those from fully innervated controls in spite of insignificant differences in plasma lipids.

In a subsequent series of experiments we analyzed the efficacy of the SNS in two strains of pigeons. White Carneau (WC) pigeons are known by their susceptibility to atherosclerosis of the aorta while Show Racer (SR) pigeons are not. Our results demonstrate that the abdominal aorta of WC pigeons has less sympathetic innervation and it declines faster with age than that of SR pigeons. The results of the described studies documenting the direct trophic influence of the SNS on the arterial wall are reinforced by the similarity to the vessel wall changes induced by partial sympathectomy and natural aging.

Trophic effect of the sympathetic nervous system on vascular smooth muscle

	Annals of Biomedical Engineering
	Springer Netherlands
ISSN	0090-6964 (Print) 1573-9686 (Online)
Issue	Volume 11, Number 6 / November, 1983

increased sensitivity to catecholamines due to sympathetic denervation

Concepts related to the pathophysiology of reflex sympathetic dystrophy syndrome (RSDS) are changing. Although sympathetic influences are still viewed as the most likely mechanism underlying the development and/or perpetuation of RSDS, these influences are no longer ascribed to an increase in sympathetic tone. Rather, the most likely mechanism may be increased sensitivity to catecholamines due to sympathetic denervation with an increase in the number and/or sensitivity of peripheral axonal adrenoceptors. Several other pathophysiological mechanisms have been suggested, including neurogenic inflammation with the release of neuropeptides by primary nociceptive afferents and sympathetic efferents. These neuromediators, particularly substance P, calcitonin gene-related peptide, and neuropeptide Y (NPY), may play a pivotal role in the genesis of pain in RSDS.

Thao Pham^, and Pierre Lafforgue
Joint Bone Spine
Volume 70, Issue 1, 1 February 2003, Pages 12-17

sympathectomy on insulin receptors and insulin action in isolated rat adipocytes

Glucose metabolism, however, was inhibited by chemical sympathectomy: the glucose transport rate was significantly reduced and fatty acid synthesis was nearly totally abolished. Insulin was still effective in stimulating both parameters but failed to restore normal levels. The results suggest that the sympathetic innervation of adipose tissue may exert an inhibitory effect on the number of high-affinity insulin receptors as well as on the sensitivity of the lipolysis to insulin, as both parameters were increased by sympathectomy. To explain the inhibitory effect of 6-hydroxydopamine treatment on glucose transport and fatty acid synthesis, a possible trophic effect of the sympathetic innervation is discussed as well as indirect mechanism counteracting the effects of the chemical sympathectomy.

Effects of chemical sympathectomy on insulin receptors and insulin action in isolated rat adipocytes

HG Joost and SH Quentin

Volume 229, Issue 3, pp. 839-844, 06/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

Effect of autonomic and adrenal manipulation on the serum insulin level

3. Journal of Tissue Research Vol. 4 (1) 83-88 (2004) Pilo, B. and Yadav, V.

Division of Neuroendocrinology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara-390 002 India. Email: bonnypilo@satyam.net.in

Mammalian glucose homoeostasis is partially controlled by glucose sensor mechanisms in the pancreatic endocrine cells and partially through autonomic nerves. The influence of the autonomic nervous system on pancreatic insulin secretion has been studied in the present study. Vagal sectioning decreased serum insulin significantly compared to that of the sham operated rats which could be the reason for the resulting hyperglycaemic condition prevailed in these rats. Bilateral adrenalectomy and chemical sympathectomy singly increased insulin level to the same extent. Even, when vagotomy was performed together with adrenalectomy, insulin level declined but this decrease is not as significant as that in vagotomized rats. Similar result was obtained with rat treated for chemical sympathectomy and vagotomy together and this slight decrease in insulin level could favour marginal hyperglycaemia.

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished; during the second minute of the cold pressor test, vascular resistance had increased by 48±20 percent in the innervated limb, whereas it had decreased by 17±5 percent in the denervated limb (P<0.02> limbs).

Figs. 1 and 2 show that L-NMMA infusion evoked a roughly 3-fold larger increase in vascular resistance in the denervated forearm than in the innervated calf. In the forearm, vascular resistance increased by 58±10 percent during L-NMMA infusion whereas in the calf, it increased only by 21±6 percent (P<0.001, forearm vs. calf). The L-NMMA induced vasoconstriction was reversed by L-arginine, but not by D-arginine, infusion (Table 1). In contrast to L-NMMA, infusion of an equipressive dose of phenylephrine increased the vascular resistance comparably in the denervated and the innervated limb (by 24±3 and 26±7 percent, respectively; P>0.5, forearm vs. calf).

Here we used subjects having undergone thoracic sympathectomy for hyperhydrosis, to probe the role of the peripheral sympathetic nervous system in the modulation of the vascular responsiveness to nitric oxide synthase inhibition. We found that sympathectomy markedly potentiated the vasoconstrictor effect of L-NMMA infusion. The L-NMMA induced vasoconstrictor effect was almost three times larger in the denervated than in the innervated limb. These findings provide the first evidence for an important interplay between the peripheral sympathetic nervous system and the L-arginine–nitric-oxide system in the regulation of the vascular tone in humans, and indicate that sympathetic innervation attenuates the vasoconstrictor effect of nitric oxide synthase inhibition.

Cardiovascular Research 1999 43(3):739-743; doi:10.1016/S0008-6363(99)00084-X
© 1999 by European Society of Cardiology

sympathectomy of peripheral nerves has been demonstrated to augment antibody response following immunization

Chemical sympathectomy of peripheral nerves has been demonstrated to augment antibody response following immunization with specific antigen.

Surgery: Basic Science and Clinical Evidence

By Jeffrey A. Norton, R. Randall Bollinger

Contributor Jeffrey A. Norton

Published by Springer, 2001

Regulation of peripheral inflammation

It is clear that the spinal adenosine effect requires intact somatic connectivity. Information on pain and inflammation in the periphery is transmitted to the nervous system, where increased spinal adenosine levels can suppress peripheral inflammation.
Experimental Neurology
Volume 184, Issue 1, November 2003, Pages 162-168

Sypathetic nervous system (SNS) modulation of immunity

Sypathetic nervous system (SNS) modulation of immunity. The role of the sympathetic nervous system in regulation of immunity is examined in mice that are chemically-denervated by injection of the neurotoxin 6-hydroxydopamine (6-OHDA). This results in a strain-dependant elevation of Th1 and Th2 cytokines and antibody titers. Denervation also results in a robust, but transient, expression of central Fos protein and corticotrophin releasing hormone, as well as an elevation in corticosterone levels in denervated mice. The interrelationships of this HPA axis activation, loss of peripheral sympathetics, and altered immune function is being explored.

Jan A. Moynihan
Associate Professor of Psychiatry, Microbiology and Immunology and of Oncology

Rice PA, Boehm GW, Moynihan JA, Bellinger DL, Stevens SY. Chemical sympathectomy alters numbers of splenic and peritoneal leukocytes. Brain Behav Immun. 16:62-73, 2002.

Rice PA, Boehm GW, Moynihan JA, Bellinger DL, Stevens SY. Chemical sympathectomy increases the innate immune response and decreases the specific immune response in the spleen to infection with Listeria monocytogenes. J Neuroimmunol 114:19-27, 2001.

Surgical sympathectomy listed as neurologic disorder

Other neurologic disorders
- Idiopathic orthostatic hypotension
- Multiple sclerosis
- Parkinsonism
- Posterior fossa tumor
- Shy-Drager syndrome
- Spinal cord injury with paraplegia
- Surgical sympathectomy
- Syringomyelia
- Syringobulbia
- Tabes dorsales (syphillis)
- Wernicke's encephalopathy
Dizziness: Classification and Pathophysiology
The Journal of Manual and Manipulative Therapy, Vol. 12, No 4 (2004)

Post-sympathectomy neuralgia: hypotheses on peripheral and central neuronal mechanisms

Post-sympathectomy neuralgia is proposed here to be a complex neuropathic and central deafferentation/reafferentation syndrome dependent on: (a) the transection, during sympathectomy, of paraspinal somatic and visceral afferent axons within the sympathetic trunk; (b) the subsequent cell death of many of the axotomized afferent neurons, resulting in central deafferentation; and (c) the persistent sensitization of spinal nociceptive neurons by painful conditions present prior to sympathectomy. Viscerosomatic convergence, collateral sprouting of afferents, and mechanisms associated with sympathetically maintained pain are all proposed to be important to the development of the syndrome.

Author Keywords: Deafferentation; Central sensitization; Viscero-somatic convergence; Ectopic discharge; Sympathetically maintained pain

Pain
Volume 64, Issue 1, January 1996, Pages 1-9

Ectopic discharge in injured nerves: comparison of trigeminal and somatic afferent

Brain Research
Volume 579, Issue 1, 1 May 1992, Pages 148-151

inhibition of sympathetic activity and a possible impairment of endothelial function

Alterations in skin microcirculation induced by brachial plexus block can be evaluated by wavelet transform of the laser Doppler flowmetry signal. Brachial plexus block reduces the oscillatory components within the 0.0095- to 0.021- and 0.021- to 0.052-Hz intervals of the perfusion signal. These alterations are related to inhibition of sympathetic activity and a possible impairment of endothelial function.

Anesthesiology:

September 2006 - Volume 105 - Issue 3 - pp 478-484

Clinical Investigations

Endothelial dysfunction, or the loss of proper endothelial function, is a hallmark for vascular diseases, and often leads to atherosclerosis.
http://en.wikipedia.org/wiki/Endothelium

Cervical sympathectomy, the method to create (experimental) vasomotor rhinitis

Unilateral and bilateral experimental vasomotor rhinitis was produced in 4 dogs with cervical sympathectomy unilaterally and bilaterally. We studied this problem from several points of view in order to explain the mechanism of vasomotor rhinitis and the relationship between upper and lower respiratory tract.

Acta Oto-laryngologica

1972, Vol. 73, No. 2-6, Pages 212-217

Axonal injury not only induces muscle weakness and loss of sensation but also leads to adaptive responses and neuropathic pain

Brain Pathol. 1999 Apr;9(2):313-25.
http://www.ncbi.nlm.nih.gov/pubmed/10219748

Peripheral nerve injury triggers a series of responses

Peripheral nerve injury triggers a series of responses in the injured nerve, such as the dissolution of distal axons, the activation of Schwann cells, the production of various proinflammatory mediators, and the infiltration of circulating immune cells. These orchestrated events regulate the degeneration and subsequent regeneration of the injured nerve. In addition, peripheral nerve injury often accompanies chronic pain. Studies in this field have revealed that spinal cord microglia activation plays a critical role in the development of pain hypersensitivity. Recent studies using genetically modified mice indicate that Toll-like receptors (TLRs) are involved in nerve degeneration (Wallerian degeneration) and chronic pain (neuropathic pain) development after nerve injury.
Curr Top Microbiol Immunol. 2009;336:169-86.
PMID: 19688334 [PubMed - indexed for MEDLINE]

Effect of sympathectomy on the expression of NMDA receptors in the spinal cord

The expression of NMDA receptors in the intermediolateral (IML) region of the upper thoracic spinal cord, was studied in 3 week old rats. The effect of section of the cervical sympathetic nerve on neuronal cell number and receptor expression was examined up to two weeks after the operation. Age-matched sham-operated and unoperated animals were used as controls. It was shown using quantitative autoradiography with the NMDA receptor antagonist [(3)H]MK-801 (dizocilpine maleate), that there was a marked downregulation of receptors in all groups of animals, beginning at approximately 4 weeks of age. However after sympathectomy, which resulted in the death of 44% of neurones in the IML by 7 days, there was a significant increase in receptor density per neurone compared to sham-operated controls. In the control animals there was a significant increase in the Kd value of the binding between 21 and 24 days after birth indicating an increased expression of a low affinity receptor, but no such increase was seen after axotomy. The results are consistent with two populations of NMDA receptors being transiently expressed in the IML in developing animals, and the higher affinity receptor being down-regulated between 4 and 5 weeks of age. The presence of the high affinity receptor subtype may predispose neurones to die after axotomy.
J Neurol Sci (1999) 169: 156-60.
http://www.ionchannels.org/showabstract.php?pmid=10540025

Sympathectomy induces adrenergic excitability of cutaneous C-fiber nociceptors

1: J Neurophysiol. 1996 Jan;75(1):514-7.

Catecholamine sensitivity of cat leg vessels after sympathectomy

by GR Ward - 1967
ajplegacy.physiology.org/content/212/2/466.full.pdf

nerve damage causes an inflammatory response

Damage to peripheral nerves often results in pain and hyperalgesia. We suggest that nerve damage causes an inflammatory response in which cells associated with the nerve release inflammatory mediators such as
eicosanoids; these mediators may contribute to the hyperalgesia which results from nerve injury. The cell types most likely to be responsible include macrophages and postganglionic sympathetic neurones.
http://www.springerlink.com/content/pjh3832058475340/
D. J. Tracey1 J. S. Walker1
School of Anatomy, University of New South Wales, 2052 Sydney, NSW, Australia

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system “talk to each other” and this process is essential for maintaininghomeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs.
http://pharmrev.aspetjournals.org/content/52/4/595.abstract

TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses

There is now good evidence to demonstrate that aberrations in tumour necrosis factor (TNF) production in vivo may be either pathogenic or protective and several plausible mechanisms may explain these contrasting activities. According to the classic pro-inflammatory scenario, failure to regulate the production of TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses, which may consequently lead to organ specific inflammatory pathology and tissue damage.
http://www.ncbi.nlm.nih.gov/pubmed/10577971

The NPY Family of Peptides in Immune Disorders, Inflammation, Angiogenesis and Cancer

NPY, NPY receptors and DPPIV in innate immunity and autoimmune disorders

Book	The NPY Family of Peptides in Immune Disorders, Inflammation, Angiogenesis and Cancer
Publisher	Birkhäuser Basel
DOI	10.1007/3-7643-7427-6
Copyright	2005
ISBN	978-3-7643-7159-3 (Print) 978-3-7643-7427-3 (Online) page 71: Lewis rats are much more likely to develop autoimmune disorders after sympathectomy (Dimitrova and Felten, 1995). This finding suggests that if sympathetic regulation were impaired in a genetically predisposed individual, an autoimmune disease might develop. Betrayal by the Brain: The Neurologic Basis of Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Related Neural Network Disorders by Jay A. Goldstein published by The Haworth Medical Press, 1996

Chest wall paresthesia affects a significant but previously overlooked proportion of patients

The rates and characteristics of the paresthesia following needlescopic VATS are similar to those observed after conventional VATS. CONCLUSIONS: Chest wall paresthesia affects a significant but previously overlooked proportion of patients following needlescopic VATS, but has minimal impact on post-operative satisfaction. Needlescopic VATS offers no apparent advantage over conventional VATS with regard to paresthesia.

http://www.ncbi.nlm.nih.gov/pubmed/15691688?dopt=Abstract

Postsympathectomy syndrome

Postsympathectomy limb pain, postsympathectomy parotid pain, and Raeder's paratrigeminal syndrome are pain states associated with the loss of sympathetic fibres and in particular with postganglionic sympathetic lesions. There is a characteristic interval of about 10 days between surgical sympathectomy and onset of pain. It is proposed that this pain in man is correlated with the delayed rise in sensory neuropeptides seen in rodents after sympathectomy. These chemical changes probably reflect the sprouting of sensory fibres and may result from the greater availability of nerve growth factor after sympathectomy. The balance between the sensory and sympathetic innervations of a peripheral organ may be determined by competition for a limited supply of nerve growth factor.

Lancet. 1985 Nov 23;2(8465):1158-60.

http://www.ncbi.nlm.nih.gov/pubmed/2414615

Melatonin levels markedly reduced after sympathectomy

In the patient with hyperhidrosis, a prominent melatonin rhythm was observed preoperatively in the CSF and plasma. After bilateral T1-T2 ganglionectomy, however, melatonin levels were markedly reduced, and the diurnal rhythm was abolished. These results provide direct evidence in humans for a diurnal melatonin rhythm in CSF and plasma as well as regulation of this rhythm by sympathetic innervation.

J Clin Endocrinol Metab 72: 819–823, 1991

Similar pathological effects of sympathectomy and hypercholesterolemia on arterial smooth muscle cells and fibroblasts

Summary: 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. Thus, similar experiments were conducted on hypercholesterolemic rabbits, which were chemically sympathectomized with 6-hydroxydopamine (n=4) or treated with vehicle for control (n=5).

Both intact and sympathectomized BA and FA developed atherosclerotic plaques, but the thickening of the intima was more advanced in sympathectomized animals, as judged by increased plaque frequency and by the phenotypic modulation of SMCs in the intima. 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

Kacem, K.¹ kamel.kacem@fsb.rnu.tn
Sercombe, R.² r.sercombe@orange.fr

Anti-inflammatory role of sympathetic nerves in chronic intestinal inflammation

Sympathectomy reduced acute DSS colitis but increased chronic DSS colitis. Sympathectomy also increased chronic colitis in II10^-/- mice. Conclusions: This study demonstrated a loss of sympathetic and an increase of SP⁺ nerve fibres in Crohn's disease. SEMA3C, a sympathetic nerve repellent factor, is highly expressed in the epithelium of Crohn's disease patients. In chronic experimental colitis, the sympathetic nervous system confers an anti-inflammatory influence. Thus, the loss of sympathetic nerve fibres in the chronic phase of the disease is most probably a pro-inflammatory signal, which might be related to repulsion of these fibres by SEMA3C and other repellents.
Straub, R. H.¹ rainer.straub@klinik.uni-regensburg.de
Gut; Jul2008, Vol. 57 Issue 7, p911-921,

Immunoglobulin producing cells in the rat dental pulp after unilateral sympathectomy

Sympathectomy results in recruitment of cells expressing κ and λ light chains into the dental pulp (P=0.005). Electron microscopy revealed these cells to be mainly plasma cells and Mott cells. We conclude that neural imbalance caused by unilateral sympathectomy recruits immunoglobulin producing cells in the dental pulp. Our results are in agreement with a model of immune regulation in which the sympathetic nervous system exerts a tonic regulatory effect over lymphocyte proliferation and migration. [Copyright &y& Elsevier]
Neuroscience; Jan2006, Vol. 136 Issue 2, p571-577, 7p

Haug, S.R. sivakami.rethnam@biomed.uib.no
Heyeraas, K.J.¹

Effect of sympathetic denervation on the rate of protein synthesis in rat skeletal muscle

Soleus isolated after 2 and 4 days of chemical sympathectomy or after 3 days of lumbar denervation showed a 17–20% statistically significant decrease in in vitro rates of protein synthesis.
American Journal of Physiology: Endocrinology & Metabolism; Apr2004, Vol. 49 Issue 4, pE642-E647, 6p

The effect of cervical sympathectomy on retinal vessel responses to systemic autonomic stimulation

The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in nine patients (eight male; mean age: 31.7 years; range: 19-58 years) with unilateral disruption of their cervical sympathetic tract. All patients had ipsilateral decreased/absent facial sweating and a Horners syndrome, evidence of unilateral sympathetic denervation. Both eyes of each patient were studied and the results were analysed in two groups: the group of nine sympathectomised eyes and the control group of unaffected fellow eyes. During handgrip contraction there was a significant difference in the mean retinal arteriolar constriction (mean +/- SEM) between the group of sympathectomised eyes (4.6 +/- 0.89%) and control eyes (7.1 +/- 1.13%), p less than 0.01. Similarly, there was a significant difference in mean venule constriction during sustained handgrip contraction between the group of sympathectomised eyes (1.5 +/- 0.67%) and control eyes (4.9 +/- 0.98%), p less than 0.05.

Eye (Lond). 1990;4 ( Pt 1):181-9.

PMID: 2323469 [PubMed - indexed for MEDLINE]

lead to hyperfunction of the serotoninergic system and pathology

We studied the balance of activity of sympathetic, parasympathetic, and serotoninergic divisions of the autonomic nervous system in the regulation of the heart function in rabbits. High activities of the sympathetic and parasympathetic system are associated with antagonistic interactions between them. Moderation of activity of these systems could be accompanied by activation of the serotoninergic system. Physiological sympathectomy and parasympathectomy lead to hyperfunction of the serotoninergic system and pathology.

Bulletin of Experimental Biology and Medicine, Vol. 140, No. 5, 2005 PHYSIOLOGY

increased blood supply is associated with decreased vascular permeability

The influence of the sympathetic nervous system on capillary permeability was studied in cats. The dye penetration from the blood through the synovial membrane was tested by perfusing the two knee joints, one of which was deprived of its sympathetic nerve supply by unilateral lumbosacral
sympathectomy.
In confirmation of previous experiments, it was found in a great majority of experiments that, in spite of marked vasodilatation, the dye excretion was considerably reduced on the sympathectomised side.
A permeability factor under the influence of the sympathetic nervous system has been postulated; its character and mechanism is still unknown.
Further unpublished experiments seem to support the view that increased blood supply is associated with decreased vascular permeability.
Res Exp Med (Berl) 173, 1--8 (1978)

Several distinct morphological alterations were observed

The ultrastructure of satellite cells of the rat superior cervical ganglion was studied following preganglionic sympathectomy. Several distinct morphological alterations were observed: (a) enlargement of the intercellular space between the ganglion cells and the satellite cells, (b) dilation of the granular endoplasmic reticulum and loss of attached ribosomes, and (c) swelling of the mitochondria with disorganization of the cristae mitochondriales. The presence of degenerating nerve fibers and synaptic boutons was also noted.

Journal of Neural Transmission 38, 43--57 (1976)

Tumor onset was significantly increased in animals sympathectomized as either neonates or as adults

Tumor Necrosis Factor, or TNF, is a cytokine which helps to kill malignant tumors. Our Norwegian orthodontists went looking into immune metabolism in rat teeth. They infected rats with bacteria which causes sores. They did a one-sided sympathectomy, to see if they could infer the role of the sympathetic nerves here. The result was that sympathetic nerves have an inhibitory effect on IL-1alpha . . .and a stimulatory effect on TNF-alpha in the intact rat pulp. (Bletsa et al. 2004)

"We showed that IL-1alpha was increased but not TNF-alpha . . .on the sympathectomized side. Both IL-1alpha and TNF-alpha were expressed in unexposed pulp. TNF-alpha was significantly decreased in the denervated incisor pulp, whereas the level of IL-1alpha remained unchanged." (Bletsa et al. 2004, emphasis added)

"Accumulating evidence suggests that the sympathetic nervous system modulates inflammatory responses and bone remodeling."(Haug et al. 2003

"Tumor onset time following implantation of MNB cells was significantly increased in animals sympathectomized as either neonates or as adults." (Fink et al. 1987)
http://editthis.info/corposcindosis/Changes_to_Systemic_Function,_part_2

alterations in the relative abundance of TH mRNA mediate changes in TH activity induced by chronic stress or sympathectomy

These results indicate that alterations in the relative abundance of TH mRNA mediate changes in TH activity induced by chronic stress or sympathectomy, and that these changes require an intact sympathetic input.

Journal of Neuroscience Research

Volume 16 Issue 1, Pages 13 - 24

Published Online: 11 Oct 2004

marked dysaesthesia over the front of the chest and in the axilla

Thirty-five patients were followed up after an average of 7.8 years (range 2-17 years). In one patient unilateral reoperation was carried out four months after the first operation. Since the first operation 34 patients had suffered from neither palmar nor axillary sweating. However 20 had permanent compensatory hyperhidrosis, and 15 suffered from gustatory facial sweating, which had usually started within six months of operation. Four, in whom two spinal thoracic nerves had also been resected, reported marked dysaesthesia over the front of the chest and in the axilla, lasting for several years.
http://www.ncbi.nlm.nih.gov/pubmed/1114879

three-phase bone scan (TPBS) after sympathectomy are identical to those reported in early RSD

Three-phase bone scan (TPBS) after sympathectomy are identical to those reported in early RSD and these alterations bear no relationship to the success of sympathectomy regarding pain relief. The mechanisms underlying alterations of TPBS as well as the potential mechanisms of sympathectomy failures are discussed.
The Clinical Journal of Pain: June 1994 - Volume 10 - Issue 2

Long-Term Denervation of Vascular Smooth Muscle Causes Not Only Functional but Structural Change

Rosemary D. Bevan, Hiromichi Tsuru

Department of Pharmacology, School of Medicine, University of California, Los Angeles, Calif.

Address of Corresponding Author

Blood Vessels 1979;16:109-112 (DOI: 10.1159/000158197)

Sympathectomy induces adrenergic excitability of cutaneous C-fiber nociceptors

Bossut DF, Shea VK, Perl ER.

J Neurophysiol 1996;75:514-7.

Sympathectomy resulted in marked reduction of dopamine beta-hydroxylase immunoreactivity

dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine,

Dbh - dopamine beta hydroxylase

Sympathectomy resulted in marked reduction of dopamine beta-hydroxylase immunoreactivity with no appreciable change in galanin immunoreactivity. ...
www.ihop-net.org/UniPub/iHOP/gs/321789.html - 342k

NASA Technical Reports Server

Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy. NASA Center: NASA (non Center Specific) ...
ntrs.nasa.gov/

Serum Dopamine-beta-Hydroxylase (DBH) Activity and Blood Pressure ...

Serum Dopamine-beta-Hydroxylase (DBH) Activity ..... Weinshilboum R, Axelrod J: Serum dopamine-^-hydroxylase: Decrease after chemical sympathectomy. ...
www.psychosomaticmedicine.org/cgi/reprint/36/4/298.pdf

dopamine-ß -hydroxylase activity in the sympathetic ganglia is blocked by surgical decentralization

PNAS | June 15, 1970 | vol. 66 | no. 2 | 453-458
Copyright © 1970 by the National Academy of Sciences

Neurally Mediated Increase in Dopamine-ß -hydroxylase Activity

Perry B. Molinoff, Steven Brimijoin, Richard Weinshilboum, and Julius Axelrod

The development of a sensitive and specific enzymatic assay for dopamine-ß -hydroxylase has enabled us to measure the activity of this enzyme in several tissues where it has not previously been measured. The administration of reserpine leads to an increase in dopamine-ß -hydroxylase activity in the rat adrenal, heart, salivary gland, and in sympathetic ganglia. The increase in the heart is preceded by a small but significant fall. We have confirmed the increase in tyrosine hydroxylase which follows the administration of reserpine and have found that the activity of phenylethanolamine-N-methyltransferase also increases after administration of this drug. The activities of two enzymes not involved in the synthesis of catecholamines, monoamine oxidase and lactate dehydrogenase, are not affected by reserpine treatment. The rise of dopamine-ß -hydroxylase activity in the sympathetic ganglia is blocked by surgical decentralization.

chemical sympathectomy with 6-hydroxy-dopamine reproduces many of the ocular phenomena of surgical sympathectomy

Anterior Segment Chemical Sympathectomy by 6-Hydroxy-Dopamine

I. Effect on Intraocular Pressure and Facility of Outflow

MONTE G. HOLLAND ¹ and JAMES L. MINIS III ¹

¹ Department of Ophthalmology, Tulane University School of Medicine, New Orleans, La.

Histofluorometric techniques have confirmed that topical ocular application of 6-hydroxydopamine, a norepinephrine congener, causes a selective and reversible destruction of sympathetic nerve terminals in the anterior segment. An investigation of the effects of "chemical sympathectomy" on the pupil, intraocular pressure, and facility of outflow showed: the pupil underwent a sequence of changes characteristic of surgical sympathetic denervation, but with a different time course; the intraocular pressure .was significantly lowered, transiently in rabbits and of longer duration in monkeys; the facility of outflow was transiently increased in monkeys and probably in rabbits; the episcleral venous pressure was unchanged in both species. It was concluded that the lowered intraocular pressure and lowered outflow pressure were the result of a reduction of aqueous inflow. There was no unequivocal experimental demonstration of supersensitization to topical norepinephrine or isoproterenol following chemical sympathetic denervation; however, the experiments were not conclusive on this important point. It was concluded that chemical sympathectomy with 6-hydroxy-dopamine reproduces many of the ocular phenomena of surgical sympathectomy. 6-Hydroxy-dopamine is a useful drug for experimental ophthalmology, and may be useful clinically.

(Investigative Ophthalmology and Visual Science. 1971;10:120-143.)
© 1971 by The Association for Research in Vision and Ophthalmology, Inc.

Chemical sympathectomy disrupts the only known neural input to the pineal gland

The Pineal Gland: A Pacemaker within the Circadian System of the House Sparrow
Natille Headrick Zimmerman and Michael Menaker
Proceedings of the National Academy of Sciences of the United States of America, Vol. 76, No. 2 (Feb., 1979), pp. 999-1003 (article consists of 5 pages)

Chemical sympathectomy disrupts the only known neural input to the pineal gland.

Serum dopamine-beta-hydroxylase and depression

Friedhelm Lamprecht¹, Michael H. Ebert¹, Ibrahim Turek^{1, 2} and Irwin J. Kopin¹

(1)	Laboratory of Clinical Science, NIMH, 20014 Bethesda, Maryland

(2)	Maryland Psychiatric Research Center, Catonsville, Maryland

Received: 18 June 1974

Abstract Serum dopamine-beta-hydroxylase (DBH) activity was studied in unipolar and bipolar depressed patients who were free of medication and in normal controls. No significant difference was found. A second group of depressed patients were studied during a course of electroconvulsive shock treatment (ECT). A small, but significant, increase in DBH activity was found 5 min after a single modified convulsion, suggesting release of DBH into the circulation. Also a small, but significant, increase in the baseline level of DBH activity was found at the ninth treatment compared to the first treatment. A single electroconvulsive shock administered to rats produced a significant elevation of both plasma epinephrine and norepinephrine at 1 and 5 min post convulsion and a significant, but smaller, elevation of plasma DBH at 5 min post convulsion in adrenalectomized rats.

Journal	Psychopharmacology
Publisher	Springer Berlin / Heidelberg
ISSN	0033-3158 (Print) 1432-2072 (Online)
Issue	Volume 40, Number 3 / September, 1974

DBH deficiency - depresssion and schizophrenia

Since norepinephrine and its receptor sites have long been postulated to play a role in a number of psychiatric disorders, the essentially normal mood and mental status of adult DBH-deficiency subjects so far encountered has elicited great interest among investigators in the area of depression and schizophrenia.

http://www.mc.vanderbilt.edu/root/vumc.php?site=adc&doc=4792

Dopamine beta-hydroxylase deficiency impairs cellular immunity

Vol. 8, No. 4, 2000

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Free Abstract Article (References) Article (PDF 227 KB)

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Original Paper

Interferon-Gamma Release in Sympathetically Denervated Rat Submaxillary Lymph Nodes
Patricia O. Castrillón^a, Daniel P. Cardinali^b, Agustín Arce^a, Rodolfo A. Cutrera^b, Ana I. Esquifino^a

Autonomic dysfunction and multiple sclerosis

Multiple Sclerosis, Vol. 7, No. 5, 327-334 (2001)
DOI: 10.1177/135245850100700509
© 2001 SAGE Publications

Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability

Peter Flachenecker
Karlheinz Reiners
Miriam Krauser
Annalaska Wolf
Klaus V Toyka
Background: Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS) but the evolution over time and the relationship to clinical characteristics are not yet established.
Objectives: We investigated the correlation of disease activity and progression of disability with composite scores of cardiovascular autonomic dysfunction and serum levels of catecholamines in a cross-sectional study of patients with clinically active and clinically stable MS.
Results: In the cross-sectional study, the number of patients with at least one abnormal sympathetic test was higher in the `active' patient group (39%) than in healthy controls (8%, P50.02) or `stable' patients (0%, P50.04), while no difference was seen in the parasympathetic score. Median catecholamine levels were significantly lower in `active' MS patients than in those with stable disease (norepinephrine, 204 ng/l (interquartile range 158-310 ng/l) vs 363 ng/l (269-507 ng/l), P50.02 and epinephrine, 23 ng/l (16-28 ng/l) vs 32 ng/l (24-107 ng/l), P50.04). In the subgroup of patients studied longitudinally, parasympathetic but not sympathetic dysfunction increased slightly during the follow-up period, with a significant correlation to the increase in clinical disability (r=0.7, P50.002).
Conclusions: Parasympathetic dysfunction was closely related to the progression of disability in patients with MS. In contrast, sympathetic dysfunction was associated to the clinical activity of MS. This is in line with previous observations suggesting that the autonomic nervous system may be intimately linked with the disordered immune regulation in MS.

Rheumatoid arthritis and Autonomic Neuropathy

Rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders may have abnormalities of sympathetic postganglionic function. Some of these patients may have autoantibodies to ganglionic acetylcholine receptors. Autoimmune thyroiditis, as with chronic thyroiditis and Hashimoto thyroiditis, can be associated with some features of Sjögren syndrome such as xerostomia. Patients with systemic sclerosis and mixed connective tissue disorder may have abnormalities of autonomic functioning of esophageal motor activity.

http://www.emedicine.com/NEURO/topic720.htm

Pain following endoscopic sympathectomy

The mean postoperative follow-up period was 11.5 months (range, 3-25 months). The hands of all patients were warm and dry after operation. No conversion to open surgery was necessary, and no operative mortality was recorded in either group. The mean inpatient pain scores were significantly higher in the biportal group (1.2 +/- 0.6) than that in the uniportal group (0.89 +/- 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.
Medical Devices & Surgical Technology Week. Atlanta: Sep 6, 2009. pg. 203

sympathectomy increased the bacterial tissue burden

sympathectomy increased the bacterial tissue burden, which was caused by a reduction in corticosterone tonus, and decreased both interleukin-4 secretion from peritoneal cells and the influx of lymphocytes into the peritoneal cavity. In both models, the peritoneal wall was the critical border for systemic infection. These results show the dual role of the sympathetic nervous system in sepsis. It can be favorable or unfavorable, depending on the innate immune effector mechanisms necessary to overcome infection.
The Journal of Infectious Diseases. Chicago: Aug 15, 2005. Vol. 192, Iss. 4; pg. 560, 13 pgs

peripheral sympathetic denervation may modulate immune function via activation of the hypothalamic-pituitary-adrenal (HPA) axis

Together, these findings suggest that peripheral sympathetic denervation may modulate immune function via activation of the hypothalamic-pituitary-adrenal (HPA) axis.

Ann N Y Acad Sci. 2000;917:923-34.

Increasing evidence suggests that the detrimental effects of glucocorticoid (GC) hypersecretion occur by activation of the hypothalamic-pituitary-adrenal (HPA) axis in several human pathologies, including obesity, Alzheimer's disease, AIDS dementia, and depression. The different patterns of response by the HPA axis during chronic activation are an important consideration in selecting an animal model to assess HPA axis function in a particular disorder.

Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits
Raber J Mol Neurobiol 1998 Aug; 18(1): 1-22

It was concluded that the cervical sympathetic nerves exert important influences on ventilation and upper airway resistance

Eur Respir J 1998; 12: 177–184.

NMDA and Sympathectomy

CONCLUSIONS: NMDA receptor is related to the induction and maitenance of neuropatic pain, and sympathetic nervous system has a main role in the already induced neuropathic pain.
The Effects of NMDA Antagonists and Sympathectomy on the c-Fos mRNA Expression in the Neuropathic Rat.
http://www.koreamed.org/SearchBasic.php?DT=1&RID=47481

Adrenal Tyrosine Hydroxylase: Compensatory Increase in Activity after Chemical Sympathectomy

Destruction of peripheral sympathetic nerve endings with 6-hydroxydopamine causes a disappearance of cardiac tyrosine hydroxylase, accompanied by a twofold increase in adrenal tyrosine hydroxylase and a small increase in phenyl-ethanolanine-N-methyl transferase.
Robert A. Mueller ¹, Hans Thoenen ¹, and Julius Axelrod ¹
Science 31 January 1969:
Vol. 163. no. 3866, pp. 468 - 469
DOI: 10.1126/science.163.3866.468

Changes in Parathyroid Hormone and Calcium Levels

Changes in Parathyroid Hormone and Calcium Levels after Superior Cervical Ganglionectomy of Rats
23-26 h after SCGx there is a significant impairment of homeostatic iPTH responses to low Ca levels which can be overcome by suitable Ca stimulus; (3) circulating catecholamines may affect denervated parathyroid cells, as revealed by the changes in serum iPTH and Ca elicited by - and -adrenoceptor-blocker treatment of SCGx rats.

Daniel P. Cardinali, Marta G. Ladizesky

Vol. 40, No. 4, 1985

Structural changes of arteries after sympathectomy

The findings indicate that in renal hypertensive rats structural changes of both large arteries and veins may develop in the absence of an intact sympathoadrenergic system.

Effect of sympathectomy on arterial and venous changes in renal hypertensive rats

G. Simon
Am J Physiol Heart Circ Physiol 241: H449-H454, 1981;

Tumor necrosis factor-a induces oligodendrocytes apoptosis

Tumor necrosis factor-a induces oligodendrocytes apoptosis, and is known to stimulate the hydrolysis of sphingomyelin to form the lipid mediator, ceramide.
http://www.springerlink.com/content/mu032lj427l85701/

Oligodendrocyte apoptosis and primary demyelination

We demonstrate that local production of TNF (tumor necrosis factor) by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology.
http://www.ncbi.nlm.nih.gov/pubmed/9736029

Denervation resulted in increased production of tumor necrosis factor-α

by TA Callahan - 2002
linkinghub.elsevier.com/retrieve/pii/S0889159100906184

cytokines mediate and control immune and inflammatory responses

Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health.
http://www.ncbi.nlm.nih.gov/pubmed/16166805

Alterations in cytokine and antibody production following chemical sympathectomy

It is becoming clear that immune responses are subject to modulation by the sympathetic nervous system. We examined the effect of chemical sympathectomy (to ablate peripheral sympathetic nerve fibers) on cytokine and Ab production in two strains of mice that are known to differ in their response to a variety of pathogens and in the dominant types of cytokines produced. C57Bl/6J mice produce a strong cell- mediated response, characterized by production of IL-2 and IFN-gamma, whereas BALB/cJ have a dominant humoral response, with production of IL- 4 and IL-10. Animals were denervated by injection with 6- hydroxydopamine and immunized with keyhole limpet hemocyanin, and spleens were removed at various times after immunization. Denervation significantly increased the keyhole-limpet-hemocyanin-stimulated in vitro proliferation and IL-2 and IL-4 production by splenocytes from both strains.
http://www.jimmunol.org/cgi/content/abstract/155/10/4613

dysregulation between the nervous and immune systems might contribute to disease development and progression

Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the ß₂ adrenergic receptor expressed on CD4⁺ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.
http://www.jleukbio.org/cgi/content/abstract/79/6/1093

TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses

There is now good evidence to demonstrate that aberrations in tumour necrosis factor (TNF) production in vivo may be either pathogenic or protective and several plausible mechanisms may explain these contrasting activities. According to the classic pro-inflammatory scenario, failure to regulate the production of TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses, which may consequently lead to organ specific inflammatory pathology and tissue damage.
http://www.ncbi.nlm.nih.gov/pubmed/10577971

Abnormal pain following nerve sprouting

Collectively, our findings indicate that as a result of autonomic sprouting due to CCI of the MN, remaining intact nociceptive fibres may potentially develop sensitivity to sympathetic and parasympathetic stimulation, which may have a role in the generation of abnormal pain following nerve injury.

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Received 22 October 2004, revised 17 February 2005, accepted 23 February 2005

Sympathectomy causes diminished capacity for physical sensation

Results: In the hot-plate analgesia test, sympathectomized rats increased their hot-plate latency time compared with that of sham-operated rats. Density of calcitonin gene-related peptide immunoreactive fibers in sympathectomy side of the lumbar dura mater decreased to 45.5% compared with the contralateral side. The number and size of calcitonin gene-related peptide immunoreactive cells in dorsal root ganglia showed no difference between sympathectomized and contralateral side.

Conclusion: Sympathectomy increased the pain threshold and made the sympathectomized rats hypesthetic.

An Anatomic Study of Neuropeptide Immunoreactivities in the Lumbar Dura Mater After Lumbar Sympathectomy.

Spine. 21(8):925-930, April 15, 1996.

Long-term superior cervical sympathectomy induces mast cell hyperplasia and increases histamine and serotonin content

Nerve fibres and mast cells are often described in close morphological and functional interactions in various organs such as the dura mater. The respective roles of mast cell activation and sympathetic impairment in cluster headache and migraine attacks have been repeatedly suggested. We have thus investigated the long-term effects of sympathectomy on mast cell morphology and content in the rat dura mater.
After unilateral ganglionectomy, the histamine content increased progressively and significantly 30–60 days post-surgery in both hemi-dura, whereas the serotonin content became significantly different from that of sham only 60 days post-surgery in the ipsilateral dura. After bilateral ganglionectomy, the histamine level significantly increased in both hemi-dura 15–60 days post-surgery, whereas the serotonin level had significantly increased at 60 days post-surgery.

These results clearly demonstrate, for the first time, a long-term trophic effect of sympathetic nerve degeneration on mast cells in the dura mater.

A. Bergerot^*, A. -M. Reynier-Rebuffel^†, J. Callebert^‡ and P. Aubineau

Copyright © 1999 IBRO. Published by Elsevier Science Ltd.

Substance P has a proinflammatory role

These studies have been carried out in a large number of patients with long-standing autoimmune diseases. It turned out that sympathetic nerve fibers are lost in chronically inflamed tissue, while substance P-positive nerve fibers sprout into the inflamed area.
Brain Behav Immun. 2007 Jul;21(5):528-34. Epub 2007 May 22.

Sympathectomy suppresses cell-mediated (T helper-1) responses

In vivo, chemical sympathectomy suppresses cell-mediated (T helper-1) responses, and may enhance antibody (T helper-2) responses. Noradrenergic innervation of spleen and lymph nodes is diminished progressively during aging, a time when cell-mediated immune function also is suppressed. In animal models of autoimmune disease, sympathetic innervation is reduced prior to onset of disease symptoms, and chemical sympathectomy can exacerbate disease severity.
Annu Rev Pharmacol Toxicol. 1995;35:417-48.

Norepinephrine activates pain pathways after nerve injury

According to MedicineNet, RSD involves "irritation and abnormal excitation of nervous tissue, leading to abnormal impulses along nerves that affect blood vessels and skin."

Animal studies indicate that norepinephrine, a catecholamine released from sympathetic nerves, acquires the capacity to activate pain pathways after tissue or nerve injury, resulting in RSD.
http://arthritis.about.com/od/rsd/a/rsd.htm

Insulin hypersensitivity produced by sympathectomy

Insulin hypersensitivity has been undeniably produced by hypophysectomy, by adrenalectomy, by sympathectomy, by spinal cord lesions, and by hypothalamic lesions.

THE HYPOTHALAMUS: A REVIEW OF THE EXPERIMENTAL DATA
W. R. Ingram
Psychosom Med, Vol. 1, Issue 1, 48-91, January 1, 1939

Indeed, local sympathectomy influences specific responses in immune organs

Brain Research
Volume 888, Issue 2, 12 January 2001, Pages 227-234

sympathetic denervation is one of the causes of Monckeberg's sclerosis regardless of diabetes mellitus

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.
Diabetologia. 1983 May;24(5):347-50, PMID: 6873514 [PubMed - indexed for MEDLINE]
Goebel FD, Fuessl HS.

Sympathectomy-induced alterations of immunity

Many studies have demonstrated that ablation of the sympathetic nervous system (SNS) alters subsequent immune responses. Researchers have presumed that the altered immune responses are predominantly the result of the peripheral phenomenon of denervation.
Activation of the CNS was determined by immunocytochemical visualization of Fos protein in brains from male C57BL/6 mice at 8, 24, and 48 h following denervation. A dramatic induction of Fos protein was found in the paraventricular nucleus (PVN) of the hypothalamus and other specific brain regions at 8 and 24 h compared to vehicle control mice. Dual-antigen labeling demonstrates that corticotrophin releasing factor (CRF)-containing neurons in the PVN are activated by chemical sympathectomy; however, neurons containing neurotransmitters which may modulate CRF neurons, such as vasopressin, tyrosine hydroxylase, and adrenocorticotropin, do not coexpress Fos. Our findings suggest an involvement of the CNS in sympathectomy-induced alterations of immunity.
Tracy A. Callahan, Jan A. Moynihan and Diane T. Piekut
Brain, Behavior, and Immunity
Volume 12, Issue 3, September 1998, Pages 230-241

chronic sympathectomy on muscle fibre composition

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.

Clin Physiol. 1988 Apr;8(2):181-91.

Supersensitivity to noradrenaline and chronic neuropathic pain conditions

Supersensitivity to noradrenaline contributes to certain vascular disorders (e.g., hypertension) and chronic neuropathic pain conditions (e.g., complex regional pain syndrome). We aimed to develop a procedure for inducing adrenergic supersensitivity that could be used to investigate the role of catecholamines in these clinical conditions.
These observations indicate that prolonged depletion of adrenergic stores by guanethidine induces adrenergic supersensitivity in cutaneous vessels, and that adrenergic supersensitivity enhances thermal hyperalgesia in the presence of noradrenaline.
Autonomic Neuroscience
Volume 88, Issues 1-2, 12 April 2001, Pages 86-93

Results support our hypothesis that blockade of the sympathetic nervous system substantially degrades ligament

2004, vol. 96, n^o2, pp. 711-718 [8 page(s) (article)] (44 ref.)