In a person who had a sympathectomy, the sympathetic component of the baroreceptor mechanism is absent

The baroreceptor reflex is only a short-term regulator of blood pressure because the receptors adapt by raising the threshold and lowering discharge rate.
8. Describe the reflex compensations when someone suddenly stands up from a supine position. What would happen in a patient who just had a sympathectomy?

Sudden standing causes pooling of blood in the leg veins. This results in decreased venous return to the heart, which leads to decreased cardiac output (Frank-Starling mechanism), which leads to decreased MAP. This decrease in MAP is detected by the carotid sinus baroreceptors, which relay a message to the medullary cardiovascular control center, which increases sympathetic outflow and decreases parasympathetic outflow, this causes:

* An increase in HR and myocardial contractility, tending to restore cardiac output.
* Vasoconstriction in skeletal musculature, skin, kidneys and gut, reducing blood flow to these organs and increasing TPR.
* Venoconstriction decreasing capacitance and increasing venous return

A patient with a sympathectomy would experience what's referred to as orthostatic hypotension (which might lead to syncope). Orthostatic hypotension is a decrease in arterial pressure when going from supine to a standing position. A person with a normal baroreceptor mechanism will try to restore MAP. In a person who had a sympathectomy, the sympathetic component of the baroreceptor mechanism is absent.

Heart Physiology II

M.A.S.T.E.R. Learning Program, UC Davis School of Medicine
Date Revised: Jan 16, 2002
Revised by: Gordon Li and Carolyn Nguyen

blunted hypoxic pulmonary vasoconstriction due to partial interruption of the sympathetic nerve supply to the lung by bilateral thoracic sympathectomy

Anaesth Intensive Care. 2003 Oct;31(5):581-3.

Orthodeoxia--an uncommon presentation following bilateral thoracic sympathectomy.

van Heerden PV, Cameron PD, Karanovic A, Goodman MA.

Source

Departments of Intensive Care and Vascular Surgery, Sir Charles Gairdner Hospital, Pharmacology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia.

Abstract

We present a case of orthodeoxia (postural hypoxaemia) which resulted from a combination of lung collapse/consolidation and blunted hypoxic pulmonary vasoconstriction due to partial interruption of the sympathetic nerve supply to the lung by bilateral thoracic sympathectomy.

http://www.ncbi.nlm.nih.gov/pubmed/14601286

Bezold-Jarisch Reflex and Sympathectomy

Much attention has been focused on the Bezold-Jarisch Reflex as the cause of sudden acute bradycardia during spinal or epidural anesthesia. The basis of this reflex is a decrease in stretch tension on mechanoreceptors located in the left ventricle. A sudden empty left ventricle triggers this paradoxical reflex which resulst in increased parasympathetic activity. Sympathetic output is also inhabited. Anything that decreases left ventricular end-diastolic volume suddenly, such as spinal anesthesia may rigger his reflex.
   By contrast, bradycardia that is slow on onset, developing after administration of spinal anesthesia, has been recognized and attributed to decreased activity of the cardioaccelerator nerves to the heart. This is a different phenomenon than the sudden bradycardia or asystole in the patient presented above. Complete sympathectomy of the heart itself reduces heart rate by about 20%.

Complications of regional anesthesia

Brendan T. Finucane

Springer, 2007 - 506 pages

An unopposed vagal tone secondary to sympathectomy

1.) An unopposed vagal tone secondary to sympathectomy. This sympathectomy occurs 2-6 dermatomes higher than sensory block, so that a sensory block of T6 can conceivably inhibit all of the sympathetic innervation to the heart.

2.) The Bezold-Jarisch reflex – which may be widely under appreciated phenomenon. You’ll be surprised how many clinicians are not well versed in this essential physiology.

Sympathectomy → reductions in venous tone → profound decreased venous return. This activates mechanoreceptors embedded within the walls of the myocardium → stimulating vagal afferents → vasomotor center of medulla → increased vagal tone to the heart, thus slowing or stopping the heart entirely to allow enough filling time to generate an effective stroke volume.
http://allnurses.com/certified-registered-nurse/sympathectomies-and-atropine-124910.html

A drastic reduction in tissue noradrenaline, adrenaline, and dopamine levels occurred after sympathectomy

Selective upper abdominal sympathectomy increased basal acid output in rats but was without effect on stimulated acid output, serum gastrin concentration, and gastric mucosal histidine decarboxylase activity. The sympathectomy was verified by fluorescence histochemistry and determination of tissue catecholamines. A drastic reduction in tissue noradrenaline, adrenaline, and dopamine levels occurred after sympathectomy, and fluorescence microscopy showed a complete loss of adrenergic nerve fibers. Vagotomy reduced catecholamine levels in the stomach wall by 50% but did not affect the catecholamine content in the pancreas and small bowel. Surprisingly, combined vagotomy and upper abdominal sympathectomy resulted in lower catecholamine levels than sympathectomy alone in extragastric but not in gastric tissues.

http://www.ncbi.nlm.nih.gov/pubmed/6515311

A depression in the heart rate and decrease in response to stress is expected to some degree in all patients after sympathectomy

A depression in the heart rate with resultant drop in the heart rate product and decrease in response to stress is expected to some degree in all patients. Some series have described this finding in most patients, whereas others report at least a 10% drop in heart rate in all patients. This is a possible major cause for postoperative dysfunction and should be cautiously sought after. Patients with resting heart rate that is below 50 to 60 beats/min should undergo electrocardiography. It is recommended that if the heart rate is low on a subsequent electrocardiogram as well, that a tilt test should be performed to exclude patients in whom there is an inordinately high risk of postoperative bradycardia.

In conclusion, thoracoscopic sympathectomy can be done as an outpatient procedure safely and efficiently. Debate continues about the correct transection levels, but at this time there is a consensus that division or clipping is equal to resection. Although the procedure has several severe side effects, they are rare. The predominant complication remains compensatory sweating, which may occur regardless of the level transected or the indication. Future clinical trials should compare some of the different techniques to achieve a global consensus of the surgical approach.

http://ats.ctsnetjournals.org/cgi/content/full/85/2/S764

The biology and control of surface overhealing

Lesions of “surface overhealing” include keloid, hypertrophic scar, and burn scar. All are characterized by overabundant collagen deposition. The biology of these lesions is reviewed, suggesting that abnormal collagen metabolism results from alterations in the inflammatory/immune response. Practical and theoretical treatment plans are outlined based on methods that alter collagen metabolism, the inflammatory/immune system or rely on physical alterations (surgery, pressure).
http://www.springerlink.com/content/3g2mr5r32m438125/

mechanisms of the post-sympathectomy syndrome and of the action of these drugs are uncertain

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

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

post-sympathectomy syndrome

Sympathectomy. Some patients with CRPS have good pain relief from sympathetic nerve blocks, but the pain relief does not last long. For these patients, doctors might suggest a sympathectomy (killing the sympathetic nerves leading to the painful body part, either by using surgery or chemicals). Some patients get longer pain relief after the sympathectomy, but others do not. Also, there is the slight chance that patients who get a sympathectomy for CRPS of the leg might develop a new pain syndrome, called post-sympathectomy syndrome. 

http://www.stoppain.org/pain_medicine/content/chronicpain/crps.asp

dennervation sensitization increases the arrhythmia susceptibility

The NA content in the heart was not measured but it is likely to be small at least at the 10-day period. It is known that three days after chemical sympathectomy NA content is only 7% of normal value [6]. Second, the development of adrenoceptor supersensitivity in the transplanted heart was demonstrated clearly with enhanced heart rate responses to NA or propranolol (at Day 10) [1]. As dennervation sensitization increases the arrhythmia susceptibility [6], it is thus possible that, in the presence of receptor supersensitivity, adrenergic activation occurs by either increase in circulating catecholamines and possibly local release of residual NA, which might still have been sufficient to contribute to arrhythmia development.
Role of sympathoadrenergic mechanisms in arrhythmogenesis
Xiao-Jun Du* and Anthony M. Dart
Baker Medical Research Institute, Melbourne, Victoria, Australia 
Cardiovascular Research 1999 43(4):832-834;

Sympathectomy altered electroactivity on the heart

The influences on the cardiac autonomic nerve system of the ETS of upper thoracic sympathetic nerve were seen to be of a lesser degree at rest. However, the response to sympathetic stimulation was suppressed after the surgery.

Eur J Cardiothorac Surg 1999;15:194-198

http://ejcts.ctsnetjournals.org/cgi/content/full/15/2/194

reduced high-frequency power after sympathetic blockade

Alternatively, reduced high-frequency power after sympathetic blockade may also be explained by diminished “accentuated antagonism,” a phenomenon described more than three decades ago (4). Heart rate response to vagal nerve stimulation is accentuated when sympathetic tone is elevated, and vice versa. Thus, cardiac sympathetic withdrawal by high spinal or epidural blockade may have resulted in diminished beat-to-beat fluctuations of R-R intervals without alteration of actual vagal nerve activity. To draw a definitive conclusion regarding the mechanism, determinations of central vagal/sympathetic outflow would be mandatory by an animal experiment.
http://www.anesthesia-analgesia.org/content/100/4/1216.2.full

1. 1.↵ 
   Tanaka M, Goyagi T, Kimura T, Nishikawa T. The effects of cervical and lumbar epidural anesthesia on heart rate variability and spontaneous sequence baroreflex sensitivity. Anesth Analg 2004;99:924–9.

    

   Abstract/FREE Full Text
2. 2.↵ 
   Introna R, Yodlowski E, Pruett J, et al. Sympathovagal effects of spinal anesthesia assessed by heart rate variability analysis. Anesth Analg 1995;80:315–21.

   Abstract/FREE Full Text
3. 3.↵ 
   Malliani A, Pagani M, Lombardi F, et al. Cardiovascular regulation explored in the frequency domain. Circulation 1991;84:482–92.

    

   Abstract/FREE Full Text
4. 4.↵ 
   Levy MN. Sympathetic-parasympathetic interactions in the heart. Circ Res1971;29:437–45.

    

   FREE Full Text

the PPG signal and the VLF fluctuations of the PPG parameters enable the assessment of the change in sympathetic nervous system activity after sympathectomy

The photoplethysmographic (PPG) signal, which measures cardiac-induced changes in tissue blood volume by light transmission measurements, shows spontaneous fluctuations. In this study, PPG was simultaneously measured in the right and left index fingers of 16 patients undergoing thoracic sympathectomy, and, from each PPG pulse, the amplitude of the pulse (AM) and its maximum (BL) were determined. The parameter AM/BL is proportional to the cardiac-induced blood volume increase, which depends on the arterial wall compliance. AM/BL increased after the thoracic sympathectomy treatment (for male patients, from 2.60±1.49% to 4.81±1.21%), as sympathetic denervation decreases arterial tonus in skin. The very low-frequency (VLF) fluctuations of BL or AM showed high correlation (0.90±0.11 and 0.92±0.07, respectively) between the right and left hands before the thoracic sympathectomy, and a significant decrease in the right-left correlation coefficient (to 0.54±0.22 and 0.76±0.20, respectively) after the operation. The standard deviation of the BL or AM VLF fluctuations also reduced after the treatment, indicating sympathetic mediation of the VLF PPG fluctuations. The study also shows that the analysis of the PPG signal and the VLF fluctuations of the PPG parameters enable the assessment of the change in sympathetic nervous system activity after thoracic sympathectomy.
http://www.springerlink.com/content/w7n21366239753l5/

sympathectomy leads to qualitative alterations in localized bone modeling and remodeling

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

http://www.ncbi.nlm.nih.gov/pubmed/8723974

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.