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. 

No significant change in tissue blood flow after sympathectomy

Lumbar sympathectomy is widely used in the treatment of peripheral vascular disease involving the lower extremity. The obvious increase in skin temperature postoperatively has led to the belief that there is a concommitant increase in perfusion of all tissues in the leg. 

Recent evidence suggests that this increase in total blood flow represents, in the main, arteriovenous shunting with a little, if any effect on the nutritive blood flow at the tissue level. Studies aimed at investigating the effect of lumbar sympathectomy on regional tissue circulation have utilized the local clearance of radioactive isotopes. No significant change in the clearance of these substances in muscle have been noted following lumbar sympathectomy in man.

Tissue Blood Flow in the Canine Lower Limb Following Lumbar SympathectomyVASC ENDOVASCULAR SURG November 1972 6: 227-238,

Inflammation after a spinal cord injury (SCI) is nonresolving

Inflammation after a spinal cord injury (SCI) is nonresolving, and can be characterized by quantification of lymphocytes using resolution indexes (Ri) and resolution plateaus (Rp), according to an experimental study published online March 22 in Brain Pathology.

Harald Prüss, M.D., 

http://www.mdnews.com/news/hd/2011_16/hd_651416

It is possible that sympathectomy affects non-immunological processes involved in tumor progression, such as extravasation, development of blood supply

Lacrimal gland, tear film, and dry eye syndromes 2: 

basic science and clinical relevance

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

 0 Reviews

Springer, 1998 - Medical - 1051 pages

Mechanism of adrenal cortex stimulation following cervical sympathectomy

http://www.ncbi.nlm.nih.gov/pubmed/14022522

Effects of right cervical sympathectomy on the ascorbic acid content of adrenals of thyroidectomized female rats

http://www.ncbi.nlm.nih.gov/pubmed/5358480

Consequences of right cervical sympathectomy on thyroid and adrenals in castrated rats

http://www.ncbi.nlm.nih.gov/pubmed/5734998

cervical sympathectomy works systemically through hypothalamus endocrine system

Background: To investigate the general action of stellate ganglion block (SGB), we examined the effects of heat stimulation and cold stress on the behavior and stress hormone of the bilateral cervical sympathectomy rats as a long-term and repeated SGB model. Methods: Wistar's male rats were divided into three groups: control (C), sham operation (S) and sympathectomy (Sx) groups. After 2 weeks, two experiments were done. One was measurement of escape response time from the heat stimulus and the other was hormone measurement. Serum adreno-corticotropic hormone (ACTH), .ALPHA.-melanocyte stimulating hormone (.ALPHA.-MSH) and .BETA.-endorphine (.BETA.-END) levels were measured assigning 3 groups to 2 subgroups with and without cold stress. Results: Escape response time was significantly extended in the Sx group. ACTH in the Sx group was significantly higher than in other groups, but changes of ACTH by cold stress were similar in 3 groups. In the Sx group .ALPHA.-MSH was hardly changed by cold stress while .ALPHA.-MSH was significantly decreased in the S group. Changes of .BETA.-END by cold stress were similar in the S and Sx groups. Conclusions: These results suggest that SGB works systemically through hypothalamus endocrine system and affects stress hormone differently. (author abst.)

http://sciencelinks.jp/j-east/article/200402/000020040204A0020288.php

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.

Influence of cervical sympathectomy and pituitary stalk section upon milk secretion in goats.

Authors

TVERSKOY, G. B.

Journal

Nature 1960 Vol. 186 No. 4727 pp. 782-84

ISSN

0028-0836

DOI

10.1038/186782a0

adult neurogenesis may contribute to the functioning, and phyio- and pathology of the CNS, particularly to the etiology of neurological diseases and disorders

Neuroinflammation is a process in which the brain responds to infections, diseases and injuries [1, 2]. Neuroinflammation involve two types of immune cells: lymphocytes, monocytes and macrophages of the hematopoietic system, and microglial cells of the CNS [3, 4]. Neuroinflammation disrupts the blood-brain barrier (BBB), allowing cells from the hematopoietic system to leave the blood stream and come in contact to the injury site [5]. The immune cells respond to injuries by eliminating debris and, synthesizing and releasing a host of powerful regulatory substances, like the complements, cytokines, chemokines, glutamate, interleukins, nitric oxide, reactive oxygen species and transforming growth factors [6-10]. The substances have both beneficial and harmful effects on the cellular environment, creating further damages [11] (fig. 1). Mature astrocytes are also activated following injury to the CNS [12, 13]. 


Chronic inflammation during depressive episodes could predispose depressive patients to neurodegenerative diseases, later in life [29].
http://www.medsci.org/v05p0127.htm

The cerebral vessels became hypersensitive to epinephrine after cervical sympathectomy

The cerebral vessels became hypersensitive to epinephrine after cervical sympathectomy.
HERTZMAN, A. B., AND DILLON, J. B.
Annual Review of Physiology
Vol. 4: 187-214 (Volume publication date March 1942)

Post-sympathectomy neuralgia is proposed here to be a complex neuropathic and central deafferentation/reafferentation syndrome

http://www.ncbi.nlm.nih.gov/pubmed/8867242

Decreased brain metabolism, rather than an increased intracranial pressure, is the cause of decreased cerebral blood flow after superior cervical sympathetic ganglionectomy

"The reduced brain metabolism and consequently reduced cerebral perfusion in the late 

postsympathectomy period could account for reduction in CSF production (Bering3)."

"In support of the above statement we mention that on the late postsympathectomy (11 to 24 months) group of dogs besides the lowered CBF 

(31.36 ml/100 gm brain weight/minute) and MCP (79.3 mm NS) also a lowered MVP (46.5 mm NS) was found. These data indicate that cervicalsympathectomy has a profound and intricate effect on the dynamics of cerebrovascular fluids and probably, in the background of all observedphenomena, a decreased cerebral metabolism as a sympathectomy effect is the underlying cause. Correspondingly the cerebral metabolic rate ofoxygen (CMR O2) decreased to 2.94 and 2.43 ml of O2/IOO gm brain weight/ minute in the sympathectomized groups." 

"Decreased brain metabolism, rather than an increased intracranial pressure, is the cause of decreased cerebral blood flow after superior 

cervical sympathetic ganglionectomy."

http://archsurg.ama-assn.org/cgi/content/summary/90/3/418

After the sympathectomy, the high night time excretion was clearly abolished

The amount of 6-sulphatoxymelatonin, the chief metabolite of melatonin, in the urine was measured in nine patients, who were subjected to bilateral sympathectomy at the second thoracic ganglionic level for treatment of hyperhidrosis of the palms. All patients showed before surgery a normal 6-sulphatoxymelatonin excretion with a peak in the excretion 
during the night time. After the sympathectomy, the high night time excretion was clearly abolished in five patients but remained high in four patients...
http://www.ncbi.nlm.nih.gov/pubmed/16647807

denervation on protein synthesis and degradation in adult rat diaphragm muscle

Previous studies showed that unilateral denervation (DNV) of the rat diaphragm muscle (DIAm) results in loss of myosin heavy chain protein by 1 day after DNV. We hypothesize that DNV decreases net protein balance as a result of activation of the ubiquitin-proteasome pathway. In DIAm strips, protein synthesis was measured by incorporation of ³H-Tyr, and protein degradation was measured by Tyr release at 1, 3, 5, 7, and 14 days after DNV. Total protein ubiquitination, caspase-3 expression/activity, and actin fragmentation were analyzed by Western analysis. We found that, at 3 days after DNV, protein synthesis increased by 77% relative to sham controls. Protein synthesis remained elevated at 5 (85%), 7 (53%), and 14 days (123%) after DNV. At 5 days after DNV, protein degradation increased by 43% relative to sham controls and remained elevated at 7 (49%) and 14 days (74%) after DNV. Thus, by 5 days after DNV, net protein balance decreased by 43% compared with sham controls and was decreased compared with sham at 7 (49%) and 14 days (72%) after DNV. Protein ubiquitination increased at 5 days after DNV and remained elevated. 

http://jap.physiology.org/content/107/2/438.full

fall in the resting membrane potential (RMP) that was identical to the effect of surgical denervation

ACh blockade using a-BuTx produced a fall in the resting membrane potential (RMP) that was identical to the effect of surgical denervation with respect to the time of onset, rate of development, and extent of change. Blockade of nerve impulses using TTX produced a similar but partial change in the RMP that began later and progressed more slowly than that of denervation. 

Similarly, the increase of extrajunctional ACh receptors following cY-BuTx-induced blockade of ACh transmission was identical to that of surgical denervation. By contrast, the effect of nerve 

impulse block using TTX was less pronounced at equivalent time points. 

Our findings indicate that specific pharmacological blockade of ACh transmission produces 

changes in the RMP and extrajunctional ACh receptors of skeletal muscle that are quantitatively equivalent to those of denervation. This suggests that ACh transmission itself mediates the nerve’s trophic regulation of these muscle properties. 

The Journal of Neuroscience,  Vol. 2, No. 2, pp. 232-243 . February 1982 

The denervation effect of smooth muscles in this instance is related to the delayed response of the smooth muscle

The denervation effect of smooth muscles in this instance is related to the delayed response of the smooth muscles and not the effect of denervation.The result, however, is the same and the four components of denervation (super-duration/delayed response, hyper-excitability, increased susceptibility and super-reactivity) are mimicked exactly by inelastic and inflexible smooth muscles. 

Autonomic nervous system: The autonomic nervous system of most fibromyalgia patients is imbalance with predominate excessive sympathetic outflows. The term dysautonomia is often used to describe these patients' S / S related to the ANS. There are significant problems related to smooth muscle dysfunctions (see effect of relaxin on smooth muscles) and the control of these organs as alluded to in the beginning of this discussion. This has to do with imbalance of the relatively increased sympathetic or decreased parasympathetic tone of the ANS. The inability of the ANS to maintain a homeostatic level of control on the smooth muscles and sphincters of many of the inner organs results in the under/ over performance of these organs. 

http://www.encognitive.com/node/12690