Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (70%) or microarterioles (30%). They were particularly enriched in the immediate vicinity (<0.25 src="http://www3.interscience.wiley.com/giflibrary/12/mgr.gif" align="absbottom" border="0">m) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis. J. Comp. Neurol. 388:444-453, 1997. © 1997 Wiley-Liss, Inc.
Roger Abounader, Edith Hamel ^*Laboratory of Cerebrovascular Research, Montreal Neurological Institute, Montréal, Québec H3A 2B4, Canada

clear association between the head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP)

In support, there is a clear association between the head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP) from the trigeminovascular system. In cluster headache there is, in addition, release of the parasympathetic neuropeptide vasoactive intestinal peptide (VIP) that is coupled to facial vasomotor symptoms. Triptan administration, activating the 5-HT_1B/1D receptors, causes the headache to subside and the levels of neuropeptides to normalise, in part through presynaptic inhibition of the cranial sensory nerves. These data suggest a central role for sensory and parasympathetic mechanisms in the pathophysiology of primary headaches. The positive clinical trial with a CGRP receptor antagonist offers a new promising way of treatment.

Lars Edvinsson^{a, ,} and Rolf Uddman^b

^aDepartment of Internal Medicine, University Hospital, S-221 85 Lund, Sweden

^bDepartment of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden

Accepted 8 September 2004.

Available online 18 November 2004.

Blocks the nerve responsible for narrowing blood vessels

Sympathectomy uses procedures that block or remove the nerve responsible for narrowing blood vessels in the hand.

http://health.nytimes.com/health/guides/disease/scleroderma/treatment-for-raynaud's-phenomenon.html

Review

A 2003 systematic review [1] looked at sympathectomy for facial blushing and the authors concluded:

We did not identify any controlled trials or cohort studies. The evidence about effectiveness, based on three case series, was therefore very limited. The main weakness of these studies was their lack of a comparison group and their resulting inability to exclude a placebo response to surgery. In addition, the methods of assessing outcome were poorly described and not validated, and the range of outcomes assessed was limited. The studies provided very limited evidence that sympathectomy improves blushing. Side effects were common.

A 2007 systematic review [2] of endoscopic thoracic sympathectomy for excessive sweating and facial blushing concluded:

The evidence of the effectiveness of ETS is weak due to a lack of randomized trials. The intervention leads to severe immediate complications in some of the patients, and to persistent side-effects for many of the patients.

http://www.clinicalanswers.nhs.uk/index.cfm?question=6881

Gustatory facial sweating subsequent to upper thoracic sympathectomy

MDShanker Nesathurai^a, , MDDavid T. Harvey^b and MDStanley W. Schatz^c

^aDepartment of Physical Medicine and Rehabilitation, McMaster University, Canada

^bMcMaster University Clinic, Hamilton Civic Hospitals, Henderson General Division, Canada

^cDepartment of Neurosurgery, McMaster University Clinic-Hamilton General Hospital, Hamilton, Ontario, Canada

Received 3 February 1994;

accepted 8 July 1994

Gustatory facial sweating has been described as a consequence of upper thoracic sympathectomy. Patients may also develop compensatory hyperhidrosis, sensory deficits, nipple hypersensitivity, and Horner's syndrome. In this article, we have reviewed three patients with reflex sympathetic dystrophy who developed gustatory facial sweating subsequent to endoscopic T2 and T3 ganglionectomy. This article also discusses the possible mechanisms of gustatory facial sweating.

keyterms: dysesthetic pain, vasomotor instability, hyperhidrosis, denervation supersensitivity.

A dysesthetic syndrome can occur after sympathectomy

Eugenia-Daniela Hord, MD, Instructor, Departments of Anesthesia and Neurology, Massachusetts General Hospital Pain Center, Harvard Medical School

A dysesthetic syndrome can occur after sympathectomy; it usually is transient but sometimes can be persistent.
Chemical sympathectomy is transient and should be used initially for diagnostic purposes to
establish the involvement of SNS and hence inhibition of sympathetic activity (eg, increased limb
temperature or ocular Horner signs) without evidence of sensory somatic blockade (eg,
hypoesthesia to pinprick and cold stimuli).

For chemical sympathectomy, 2 basic techniques are used.
Injections of local anesthetic around sympathetic paravertebral ganglia that project to the
affected body part (sympathetic ganglion block): This will affect all components of the
sympathetic outflow to an extremity (adrenergic vasoconstrictor, cholinergic sudomotor, and adrenergic pilomotor).

Intravenous regional block: This will prevent the release of only norepinephrine from the sympathetic terminals within the region of application (ie, distal to the tourniquet).

Effect of sympathetic denervation on the rate of protein synthesis

Rates of protein synthesis were investigated in skeletal muscles from rats submitted to chemical and surgical sympathectomy. Three models of sympathetic denervation were used: 1) treatment with guanethidine (100 mg·kg^-1·day^-1 sc); 2) lumbar sympathetic denervation (surgical excision of the second and third lumbar ganglia of the sympathetic chain, from which arises the postganglionic fibers to the skeletal muscles of rat hindlimb); and 3) adrenodemedullation. Protein synthesis was estimated in isolated soleus muscle by the rate of incorporation of [¹⁴C]tyrosine (0.1 mM, 0.05 µCi/ml) into total protein. 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. These effects were reverted by addition of 10^-5 M isoproterenol or epinephrine in vitro. Neither clenbuterol nor isoproterenol (10^-7, 10^-6, or 10^-5 M) in vitro affected the rate of protein synthesis in soleus from normal rats. On the other hand, clenbuterol or epinephrine (10^-5 M) increased by 20% the rate of protein synthesis in soleus muscles from adrenodemedullated rats and prevented its decrease in muscles from fasted rats. The data suggest that the sympathetic nervous system stimulates protein synthesis in oxidative muscles, probably through the activation of ₂-adrenoceptors, especially in situations of hormonal or nutritional deficiency.
Luiz Carlos C. Navegantes, Neusa M. Z. Resano, Amanda M. Baviera, Renato H. Migliorini, and Isis C. Kettelhut
Am J Physiol Endocrinol Metab 286: E642-E647, 2004

Evaluation of long-term chemical sympathectomy

AJP - Heart and Circulatory Physiology, Vol 238, Issue 4 527-H532, Copyright © 1980 by American Physiological Society

K. Fronek

Administration of 6-hydroxydopamine (6-OHDA) will produce long-term sympathectomy in newborn animals. This investigation was designed to determine whether or not a long-term sympathectomy can be achieved by repeated administration of 6-OHDA in adult rabbits. Chronic treatment with 6-OHDA lowered blood pressure on average of 9 mmHg; the carotid sinus reflex was depressed, in contrast to the pressure response to intravenously administered epinephrine, which was doubled. In a constant-flow hindlimb preparation, the response to norepinephrine (NE) in 6-OHDA-treated rats was 50% larger and lasted 3 times longer. NE uptake in vitro, which is proportional to the number of adrenergic nerve endings, was found to be diminished by 80-85% in aortas from 6-OHDA-treated animals, and the dose-response curve for NE was slightly shifted to the left. The number of ganglionic cells in the superior cervical ganglia in treated animals was decreased by 80%. In conclusion, results from 6-OHDA-treated adult animals were entirely consistent with the effects of long-term sympathectomy.

Effects of 6-hydroxydopamine on dopamine and noradrenaline content

Naunyn-Schmiedeberg's Archives of Pharmacology

Volume 329, Number 3 / May, 1985

P. Soares-da-Silva¹ and R. Davidson¹

(1)	Laboratorio de Farmacologia, Faculdade de Medicina, P-4200 Porto, Portugal

Received: 29 October 1984 Accepted: 27 January 1985

6-OHDA and pargyline plus 6-OHDA induced a parallel decrease of the noradrenaline and dopamine content in the main trunk of the mesenteric artery, femoral artery and heart. In the proximal branches of the mesenteric artery, renal and splenic arteries 6-OHDA selectively reduced noradrenaline (by 50%) without changes in dopamine levels. Previous treatment with pargyline abolished this selectivity and depleted the tissue levels of both noradrenaline and dopamine by 75%.

The present findings suggest: an independent dopamine presence in the proximal branches of the mesenteric artery, renal artery and splenic artery; that noradrenaline and dopamine are in one and the same structure in the heart, femoral artery and the main trunk of the mesenteric artery; the saphenous vein is more resistant to chemical sympathectomy than arterial blood vessels; the changes in plasma catecholamine concentrations are probably related to a compensatory mechanism initiated at the adrenal medulla.

Alteration of antioxidant status following sympathectomy: Differential effects of modified plasma levels of adrenaline and noradrenaline

Molecular and Cellular Biochemistry
Volume 152, Number 1 / November, 1995
Philip M. Toleikis¹ and David V. Godin
Department of Pharmacology and Therapeutics, The University of British Columbia, V6T 1Z3 Vancouver, B.C., Canada

Differences between adrenalectomy and 6-OH treatment on antioxidant components are suggestive of differential actions of adrenaline and noradrenaline on tissue antioxidant status which may have important implications under conditions associated with elevations in levels of these catecholamines including chronic stress and myocardial infarction.