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PubMed2004

Immunohistochemical determination of the sympathetic pathway in the orbit via the cranial nerves in humans.

OBJECT: The present study was undertaken to elucidate the extent and precise distribution of the postganglionic sympathetic fibers in the cranial nerves projecting to the orbit and to reconstruct sympathetic routes in the orbit in humans. For this purpose, the authors made an immunohistochemical determination of the sympathetic fibers by using an antibody against norepinephrine-synthetic enzyme, tyrosine hydroxylase (TH). METHODS: Specimens containing the orbit and the cavernous sinus were obtained from formalin-fixed human cadavers. First, it was confirmed that the superior cervical ganglion contained strongly immunostained TH-positive neuronal cell bodies and fibers. After careful dissection of the cranial nerves projecting to the orbit, different segments of each cranial nerve were processed for immunohistochemical analysis for TH. All of the intraorbital cranial nerves contained TH-positive sympathetic fibers, although the amounts were very different in each cranial nerve. At the proximal site of the common tendinous ring, TH-positive fibers were found mainly in the abducent and trochlear nerves. At the distal site of this ring, TH-positive fibers were lost or markedly reduced in number in the abducent and trochlear nerves and were distributed mostly in the ophthalmic and oculomotor nerves. Among the cranial nerves projecting to the orbit, the ophthalmic nerve and its bifurcated nerves--frontal, lacrimal, and nasociliary--contained numerous TH-positive fibers. CONCLUSIONS: The authors conclude that the postganglionic sympathetic fibers are distributed to all cranial nerves projecting to the orbit and that the ophthalmic nerve provides a major sympathetic route in the orbital cavity in humans.

Abducens Nerve↗
PubMed1992

Peptide-containing nerves in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjögren's syndrome patients were compared with those in salivary glands from 7 healthy controls. METHODS: Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P. RESULTS: Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION: This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.

C-Peptide↗
PubMed1996

Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model.

The extent of the sprouting of sympathetic postganglionic fibers in the dorsal root ganglion (DRG) and the peripheral nerves was examined in neuropathic rats at different postoperative times. After the L5 and L6 spinal nerves were ligated on one side, three different pain behavior tests (representing mechanical allodynia, cold allodynia, ongoing pain exacerbated by cold stress) were performed at various time intervals. The sympathetic postganglionic fibers were visualized by immunostaining with antibodies to tyrosine hydroxylase (TH). In the neuropathic rats, all three pain behaviors were fully developed within 3 days after the surgery, maintained up to 2 weeks, and then started to decline gradually afterward. At 20 weeks after neuropathic surgery, pain behaviors were reduced significantly compared to the peak response, but were still higher than the presurgery levels. Sympathectomy, performed 4 days after neuropathic surgery, almost completely abolished the signs of mechanical allodynia and ongoing pain behaviors, and it reduced the behaviors of cold allodynia to approximately half. The numerical density of sympathetic fibers in the DRG of an injured segment was significantly higher at 1, 4, and 20 weeks after neuropathic surgery as compared to the normal, suggesting that there is sprouting of sympathetic fibers in the DRG after peripheral nerve injury. Sprouting of sympathetic fibers in the DRG was extensive as early as 2 days after the spinal nerve ligation, and the sprouted fibers were almost completely eliminated after sympathectomy. The data suggest that sympathetic innervation of the DRG may play an important role in the development and maintenance of sympathetically maintained neuropathic pain.

Animals↗
PubMed2001

Peripheral effects of morphine in neuropathic rats: role of sympathetic postganglionic nerve fibers.

We studied the contribution of peripheral opioid receptors to the morphine-induced antinociception in rats with a spinal nerve ligation-induced neuropathy. Intraplantar (i.pl.) injection of morphine produced a stronger suppression of nociceptive reflex responses of the neuropathic limb following ipsilateral, than contralateral, administration, whereas the morphine-induced effect on the control limb was independent of the injection side. Antinociception induced by systemically administered morphine was significantly attenuated by i.pl. injection of a peripherally acting opioid receptor antagonist in neuropathic but not in sham-operated rats. Following chemical sympathectomy with 6-hydroxydopamine, antinociception was achieved at a lower dose ipsilaterally, than contralaterally, following i.pl. administration of morphine, and the morphine-induced antinociception was attenuated by a peripherally acting opioid receptor antagonist. These results indicate that peripheral opioid receptors may contribute to the morphine-induced antinociception in the spinal nerve ligation-induced model of neuropathy. Sympathectomy of the neuropathic limb may underlie, at least partly, the increased peripheral efficacy of morphine in neuropathy.

Analgesics, Opioid↗
PubMed2005

Ultrastructural identification of a sympathetic component in the hypoglossal nerve of hamsters using experimental degeneration and horseradish peroxidase methods.

We employed experimental degeneration, tract-tracing with wheatgerm agglutinin conjugated with horseradish peroxidase (WGA-HRP) and electron microscopy to explore the postganglionic sympathetic fibers in the hypoglossal nerve of hamsters. Quantitative results of normal untreated animals at the electron microscopic level showed the existence of unmyelinated fibers, which made up about 20% of the total fibers in the nerve, being more numerous on the left side. The nerve fibers were preferentially distributed at the periphery of the nerve. Following superior cervical ganglionectomy, most of the unmyelinated fibers underwent degenerative changes. Tract-tracing studies showed that some of the unmyelinated fibers were labeled by WGA-HRP injected into the superior cervical ganglion (SCG). It is suggested that the unmyelinated fibers represent the postganglionic sympathetic fibers originated from the SCG.

Animals↗
PubMed1998

Comparison of sympathetic sprouting in sensory ganglia in three animal models of neuropathic pain.

Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after peripheral nerve injury. Therefore, one possible contributing factor of sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting in the DRG after peripheral nerve injury. The present study compared the extent of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in three rat neuropathic pain models: (1) the chronic constriction injury model (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the segmental spinal nerve ligation injury model (SSI). All three methods of peripheral nerve injury produced behavioral signs of ongoing and evoked pain with some differences in the magnitude of each pain component. The density of sympathetic fibers in the DRG was significantly higher at all examined postoperative times than controls in the SSI model, while it was somewhat higher than controls only at the last examined postoperative time (20 weeks) in the CCI and PSI models. Therefore, data suggest that, although sympathetic changes in the DRG may contribute to neuropathic pain syndromes in the SSI model, other mechanisms seem to be more important in the CCI and PSI models at early times following peripheral nerve injury.

Animals↗
PubMed1996

Muscle reflex stimulates sympathetic postganglionic efferents innervating triceps surae muscles of cats.

Two neural mechanisms contribute to the cardiovascular responses to exercise. The first, central command, proposes a parallel activation of central locomotor and brain stem circuits controlling cardiovascular function. The second, the muscle reflex, proposes that contraction-activated group III and IV afferents increase cardiovascular function. In humans, whole nerve recordings of sympathetic discharge suggest that central command increases sympathetic outflow to skin but not to skeletal muscle and that the muscle reflex increases sympathetic outflow to skeletal muscle but not to skin. We therefore tested the hypothesis that the muscle reflex, but not central command, increases the discharge of single sympathetic postganglionic efferents innervating the triceps surae muscles of decerebrate unanesthetized cats. Central command was evoked by electrical stimulation of the mesencephalic locomotor region. The reflex was evoked by electrical stimulation of the tibial nerve, which in turn contracted the triceps surae muscles. Hexamethonium abolished spontaneous and evoked activity, verifying that the recordings were from sympathetic postganglionic fibers. The discharge of 13 efferents was increased by static contraction (from 0.6 +/- 0.2 to 1.0 +/- 0.3 imp/s; P < 0.05) but was not increased by central command (from 0.6 +/- 0.2 to 0.8 +/- 0.2 imp/s; P > 0.05). Nevertheless, the discharge of nine efferents, not increased by central command before alpha-adrenergic blockade (from 0.5 +/- 0.2 to 0.9 +/- 0.4 imp/s; P > 0.05), was increased after blockade (from 1.3 +/- 0.2 to 3.2 +/- 0.8 imp/s; P < 0.05). We conclude that the muscle reflex stimulates sympathetic postganglionic efferents innervating the vasculature of skeletal muscle. Furthermore, baroreceptors appear to buffer the central command-induced increases in the discharge of these efferents.

Animals↗
PubMed1993

[Markedly decreased cardiac uptake with 123I-MIBG scintigraphy in a case of pure progressive autonomic failure].

A 70-year-old man with about 25 years' history of autonomic nervous system disturbances including orthostatic hypotension is presented. He had had no extrapyramidal and cerebellar signs, and was diagnosed as having pure progressive autonomic failure. His cardiac imaging with 123I labeled MIBG (metaiodobenzylguanidine) showed extremely diminished uptake, but the imaging with 201-thallium showed a normal cardiac uptake. Those results indicate non-cardiac disease-associated (neurogenic) postganglionic sympathetic fiber abnormality innervating the heart. Also, adrenomedullary imaging with 123I labeled MIBG showed no adrenal image, which suggests the possibility that there should be dysfunction in the adrenal medulla of this patient. This imaging study is thought to be useful for evaluating autonomic nervous system function in neurologic diseases.

3-Iodobenzylguanidine↗
PubMed2003

Control of postganglionic sympathetic efferent fibers by neurokinin 1 receptors in rats.

Substance P (SP) is released peripherally from nociceptive terminals and has a direct effect on vascular cells. The present study suggests an indirect effect as well. In normal rats and rats with one hindpaw inflamed for 48 h following intraplantar injection of complete Freund's adjuvant, neurokinin 1 (NK1) receptors were immunohistochemically localized on postganglionic sympathetic axons. The percentage of NK1-labeled axons in the gray rami from normal rats was 35.0+/-5.0; in inflamed rats this percentage increased significantly to 49.1+/-2.3. These data suggest a sensory-sympathetic reflex, where SP activates these peripheral sympathetic receptors with subsequent release of noradrenaline and other compounds to affect vascular cells indirectly. This control is enhanced after inflammation.

Animals↗
PubMed1993

The amplitude of synchronized cardiac sympathetic nerve activity reflects the number of activated pre- and postganglionic fibers in anesthetized cats.

In order to obtain information regarding the number of pre- and postganglionic fibers that are firing, we measured cardiac sympathetic nerve activity (CSNA) before and after the successive sectioning of T1-T5 thoracic rami in anesthetized cats. Total activity from the area was measured under the mean CSNA curve. Peak amplitude, width and periodicity of the synchronized discharge was analyzed from the CSNA curve by the method we developed. Total CSNA decreased to 91 +/- 6%, 63 +/- 6%, 27 +/- 10%, 8 +/- 6% and < 1% of the control due to successive section of the T5, T4, T3, T2 and T1 rami, respectively. The peak amplitude of synchronized CSNA decreased to 95 +/- 6%, 73 +/- 8%, 40 +/- 5% and < 10% of the control value, due to section of the T5, T4, T3 and T2 rami, respectively. The control width was 107 +/- 8 ms and decreased to 106 +/- 1 ms, 92 +/- 6 ms and 68 +/- 5 ms by successive section of the respective T5, T4 and T3 rami. However, periodicities of 80-120 ms (Tc rhythm) and 140-500 ms (Tb rhythm) of synchronized CSNA remained unchanged after section of the T3-T5 rami. The total CSNA decreased gradually due to decreases in the peak amplitude and width of synchronized CSNA with the successive section of preganglionic fibers. These results indicate that the peak amplitude of synchronized CSNA reflects the number of pre- and post-ganglionic fibers that are firing and suggest that the number of preganglionic neurons which activate the cardiac fibers naturally was largest in the T3 segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1991

[Microneurographic study of sympathetic nerve activity of the lower leg in lumbar spine diseases].

Sympathetic nerve activity was recorded with micro-neurography, and this activity in lumbar spine disease was evaluated. The recording was made with 2-5 omega impedance tungsten microelectrodes in human common peroneal nerve. Sympathetic nerve activity was expressed as bursts numbers per minute, and bursts per 100 heart beats. For the skin sympathetic nerve activity, reflex latencies were 0.80 +/- 0.16 seconds. These values were clearly longer than those of myelinated A fiber, reflecting the conduction velocities of unmyelinated C fiber that forms postganglionic sympathetic fiber. Muscle sympathetic nerve activity in lumbar spine disease with leg symptoms increased in comparison with other subjects. These results suggest this condition induces latent ischemia of the leg that may cause coldness or numbness in the leg.

Action Potentials↗
PubMed1999

Light and electron microscopic immunocytochemical study on the innervation of the pineal gland of the tree shrew (Tupaia glis), with special reference to peptidergic synaptic junctions with pinealocytes.

Conventional and immunocytochemical, light- and electron-microscopic studies on the innervation of the pineal gland of the tree shrew (Tupaia glis) were made. Neuropeptide Y (NPY)-immunoreactive fibers, which were abundantly distributed in the gland, disappeared almost completely after superior cervical ganglionectomy, suggesting that these fibers are mostly postganglionic sympathetic fibers. By contrast, tyrosine hydroxylase (TH)-immunoreactive fibers, which were less numerous than NPY-fibers, remained in considerable numbers in ganglionectomized animals, indicating the innervation of TH-positive fibers from extrasympathetic sources. Bundles of substance P (SP)- or calcitonin gene-related peptide (CGRP)-immunoreactive fibers, entering the gland at its distal end, were left intact after ganglionectomy. SP-fibers were numerous, but CGRP-fibers were scarce in the gland. SP-immunoreactive fibers were myelinated and nonmyelinated, and were regarded as peripheral fibers because of the presence of a Schwann cell sheath. NPY- and SP-immunoreactive fibers and endings were mainly localized in the pineal parenchyma. NPY-immunoreactive endings synapsed frequently, and SP-positive ones did less frequently, with the cell bodies of pinealocytes. The results suggest that NPY and SP directly control the activity of pinealocytes. Sections stained for myelin showed that thick and less thick bundles of myelinated fibers entered the gland by way of the habenular and posterior commissures, respectively. Under the electron microscope, the bundles were found to contain also unmyelinated fibers. A considerable number of nerve endings synapsing with the cell bodies of pinealocytes remained in ganglionectomized animals; these endings were not immunoreactive for TH or SP. Such synaptic endings may be the terminals of commissural fibers.

Animals↗
PubMed1988

Distribution of noradrenergic nerve fibers in canine nasal mucosa following selective neurectomies.

In this study, we have used noradrenergic histofluorescence and selective neurectomies of the vidian, ethmoid and caudal nasal nerves to evaluate the distribution of postganglionic sympathetic fibers in the canine nasal mucosa. In conjunction with the histochemical localization of the noradrenergic fibers in the nasal mucosa after vidian neurectomy, the norepinephrine content of the mucosa was also evaluated using high-performance liquid chromatography. Unilateral neurectomy of the superior cervical ganglion (SCG) resulted in the unilateral disappearance of all noradrenergic histofluorescence in the nasal mucosa, while no morphological changes in noradrenergic fibers could be identified after neurectomy of the cervical sympathetic trunk 1 cm below the SCG. Ethmoid neurectomy caused the disappearance of noradrenergic fibers of the upper third of the nasal mucosa, while vidian neurectomy resulted in a partial loss of noradrenergic fibers in the lower two-thirds of the nasal mucosa. The loss was chiefly in the area adjacent to venous sinusoids and was responsible for 50% of the norepinephrine content of this tissue. We concluded that all the postganglionic sympathetic fibers are from the ipsilateral SCG. Some of them travel via the ethmoid nerve and innervate the upper third of the nasal mucosa. The remaining fibers travel via the vidian nerve and perhaps the vessel walls of the supplying arteries and innervate the lower two-thirds of the nasal mucosa. The vidian nerve chiefly innervates the venous sinusoids of the lower two-thirds of the nasal mucosa.

Adrenergic Fibers↗
PubMedDate not supplied

Sympathetic skin response in Parkinson's disease.

Sudomotor function in 83 patients with Parkinson's disease (PD) was evaluated using the sympathetic skin response (SSR) and sweat response to intradermal acetylcholine (ACh) injection. The incidence of abnormal SSRs (36.1%) increased, and the size of the response decrease with the severity of the illness. Neither the incidence of abnormal SSRs nor the amplitudes of the responses were influenced by levodopa or an anticholinergic agent. The SSR therefore can be used to evaluate the sudomotor efferent pathway in PD patients. In all the patients who had no SSR response, the local sweat response to ACh showed a reduced number of excitable sweat glands and low sweat volume. One patient, whose local sweat response to ACh was markedly impaired, had unmyelinated and acetylcholinesterase-positive fiber densities that were in the normal range in his biopsied sural nerve. The abnormal sweat response to ACh is considered to reflect the dysfunction of postganglionic sympathetic fibers in PD patients.

Acetylcholine↗
PubMed1996

Neural control of the pineal gland.

The rhythm in melatonin production by the mammalian pineal gland is generated by the circadian timing system. The components of that system which mediate the function are: (1) visual projections through the retinohypothalamic tract to the circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus; (2) the SCN which generates a circadian signal transmitted by SCN projections to the parvocellular autonomic component of the paraventricular nucleus; (3) paraventricular nucleus projections to the upper thoracic intermediolateral cell column; (4) preganglionic sympathetic fibers to the superior cervical ganglion; (5) postganglionic sympathetic fibers from the superior cervical ganglion to the pineal.

Animals↗
PubMed1987

Retrograde axonal transport of true blue dye by the peripheral autonomic nerves in canine nasal mucosa.

In this study we employed retrograde axonal transport of (E)-2,2'-vinylendi-benzofuran-5-carboxamidin-diaceturate+ ++ or true blue (TB) to study the peripheral autonomic innervation of the canine nasal mucosa. After injection of TB into the nasal mucosa, labeled neurons were found in the ipsilateral sphenopalatine ganglion (SPG) and the superior cervical ganglion (SCG). There were no labeled neurons in the middle cervical or stellate ganglia. This indicated that the origin of the postganglionic sympathetic fibers of the nasal mucosa was only from the ipsilateral SCG. When TB was injected into the nasal mucosa of dogs following a caudal or ethmoidal neurectomy, labeled neurons could still be found in the SPG and SCG. When TB was injected into the nasal mucosa of dogs following ethmoidal and vidian neurectomies or with maxillary neurectomy added, some labeled neurons could still be found in both the ipsilateral SPG and SCG. These results support the concept that another pathway--perhaps perivascular--exists for postganglionic sympathetic fibers other than the vidian and ethmoidal nerves. Labeled neurons were still observed in SPG when TB was applied to the canine nasal mucosa following neurectomy of either the ethmoidal or the caudal nasal nerve. However, retrograde labeled neurons could not be found in SPG following simultaneous neurectomies of the ethmoidal and caudal nasal nerves. These results show that the postganglionic parasympathetic fibers originating in the SPG travel along the ethmoidal and caudal nasal nerves.

Animals↗
PubMed1994

Immunohistochemical studies on sympathetic and non-sympathetic nerve fibers and neuronal cell bodies in the pineal gland of cotton rats, Sigmodon hispidus.

Immunohistochemistry revealed the presence of tyrosine hydroxylase (TH)-, neuropeptide Y (NPY)-, calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive nerve fibers and SP-immunoreactive neuronal cell bodies in the pineal gland of the cotton rat (Sigmodon hispidus). Abundant TH- and NPY-immunoreactive fibers were distributed evenly throughout the gland; less numerous CGRP- and SP-immunoreactive fibers were distributed in the superficial pineal and the stalk, but were scarce in the deep pineal. All the immunoreactive fibers were usually found around blood vessels. Since TH- and NPY-immunoreactive fibers in various pineal regions disappeared completely with superior cervical ganglionectomy, these fibers are all considered postganglionic sympathetic fibers. Intrapineal CGRP- or SP-immunoreactive fibers decreased considerably in number following superior cervical ganglionectomy, suggesting that some sympathetic fibers contain CGRP or SP. Bilateral bundles of nerve fibers under the transverse sinuses, corresponding to the nervi conarii, contained TH-, NPY-, CGRP- and SP-immunoreactive fibers, which continued into those distributed in the pineal capsule. In the nervi conarii, fibers immunoreactive for TH and NPY disappeared after superior cervical ganglionectomy, but those immunoreactive for CGRP and SP persisted. Thus, non-sympathetic, CGRP- and SP-immunoreactive fibers, together with sympathetic fibers, are presumed to enter the gland by way of the nervi conarii. Neuronal cell bodies, containing SP-like immunoreactivity and being possibly parasympathetic in nature, occurred occasionally in the superficial pineal.

Animals↗