Origin of sensory and autonomic innervation of the rat temporomandibular joint: A retrograde axonal tracing study with the fluorescent dye fast blue

Previous studies that have used retrograde axonal tracers (horseradish peroxidase alone or conjugated with wheat germ agglutinin) have shown that the temporomandibular joint (TMJ) is supplied with nerve fibers originating mainly from the trigeminal ganglion, in addition to other sensory and sympathetic ganglia. The existence of nerve fibers in the TMJ originating from the trigeminal mesencephalic nucleus is unclear, and the possible innervation by parasympathetic nerve fibers has not been determined. In the present work, the retrograde axonal tracer, fast blue, was used to elucidate these questions and re-evaluated the literature data. The tracer was deposited in the supradiscal articular space of the rat TMJ, and an extensive morphometric analysis was performed of the labeled perikaryal profiles located in sensory and autonomic ganglia. This methodology permitted us to observe labeled small perikaryal profiles in the trigeminal ganglion, clustered mainly in the posterior-lateral region of the dorsal, medial and ventral thirds of horizontal sections, with some located in the anterior-lateral region of the ventral third. Sensory perikarya were also labeled in the dorsal root ganglia from C2 to C5. No labeled perikaryal profiles were found in the trigeminal mesencephalic nucleus. on the other hand, autonomic labeled perikaryal profiles were distributed in the sympathetic superior cervical and stellate ganglia, and parasympathetic otic ganglion. Our results confirmed those of previous studies and also demonstrated that: (i) there is a distribution pattern of labeled perikaryal profiles in the trigeminal ganglion; (ii) some perikaryal profiles located in the otic ganglion were labeled; and (iii) the trigeminal mesencephalic nucleus did not show any retrogradely labeled perikaryal profiles.

The role of membranous urethral afferent autonomic innervation in the continence mechanism after nerve sparing radical prostatectomy: a clinical and prospective study

Purpose: We evaluated the somatic and autonomic innervation of the pelvic floor and rhabdosphincter before and after nerve sparing radical retropubic prostatectomy using neurophysiological tests and correlated findings with clinical parameters and urinary continence. Materials and Methods: From February 2003 to October 2005, 46 patients with prostate cancer were enrolled in a controlled, prospective study. Patients were evaluated before and 6 months after nerve sparing radical retropubic prostatectomy using the UCLA-PCI urinary function domain and neurophysiological tests, including somatosensory evoked potential, and the pudendo-urethral, pudendo-anal and urethro-anal reflexes. Clinical parameters and urinary continence were correlated with afferent and efferent innervation of the membranous urethra and pelvic floor. We used strict criteria to define urinary continence as complete dryness with no leakage at all, not requiring any pads or diapers and with a UCLA-PCI score of 500. Patients with a sporadic drop of leakage, requiring up to 1 pad daily, were defined as having occasional urinary leakage. Results: Two patients were excluded from study due to urethral stricture postoperatively. We evaluated 44 patients within 6 months after surgery. The pudendo-anal and pudendo-urethral reflexes were unchanged postoperatively (p = 0.93 and 0.09, respectively), demonstrating that afferent and efferent pudendal innervation to this pelvic region was not affected by the surgery. Autonomic afferent denervation of the membranous urethral mucosa was found in 34 patients (77.3%), as demonstrated by a postoperative increase in the urethro-anal reflex sensory threshold and urethro-anal reflex latency (p <0.001 and 0.0007, respectively). Six of the 44 patients used pads. One patient with more severe leakage required 3 pads daily and 23 showed urinary leakage, including 5 who needed 1 pad per day and 18 who did not wear pads. Afferent autonomic denervation at the membranous urethral mucosa was found in 91.7% of patients with urinary leakage. Of 10 patients with preserved urethro-anal reflex latency 80% were continent. Conclusions: Sensory and motor pudendal innervation to this specific pelvic region did not change after nerve sparing radical retropubic prostatectomy. Significant autonomic afferent denervation of the membranous urethral mucosa was present in most patients postoperatively. Impaired membranous urethral sensitivity seemed to be associated with urinary incontinence, particularly in patients with occasional urinary leakage. Damage to the afferent autonomic innervation may have a role in the continence mechanism after nerve sparing radical retropubic prostatectomy.

Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype

AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Morphological and quantitative study of ganglionated plexus of Calomys callosus trachea

Calomys callosus is a wild, native forest rodent found in South America. In Brazil, this species has been reported to harbour the parasitic protozoan Trypanosoma cruzi. The ganglionated plexus of this species was studied using whole-mount preparations of trachea that were stained using histological and histochemical methods. The histological methods were used to determine the position of the ganglia with respect to the trachea muscle and to determine the presence of elastic and collagen fibers. The histochemical method of NADH-diaphorase was used for morphometric evaluations of the plexus. The tracheal plexus lies exclusively over the muscular part of the organ, dorsal to the muscle itself. It varies in pattern and extent between animals. The average number of neurons was 279 and the cellular profile area ranged from 38.37 mu m(2) to 805.89 mu m(2). Acetylcholinesterase (AChE) histochemistry verified that both ganglia and single neurons lie along nerve trunks and are reciprocally interconnected with the plexus. Intensely AChE-reactive neurons were found to be intermingled with poorly reactive ones. Two longitudinal AChE-positive nerve trunks were also observed and there was a diverse number of ganglia along the intricate network of nerves interconnecting the trunks. A ganglion capsule of collagen and elastic fibers surrounding the neurons was observed. Under polarized light, the capsule appeared to be formed by Type I collagen fibers. (C) 2008 Elsevier B.V. All rights reserved.

Sympathetic control of accommodation:evidence for inter-subject variation

Autonomic innervation of ciliary smooth muscle is mediated principally by the parasympathetic nervous system and is supplemented by the sympathetic nervous system. Previous drug and nerve stimulation experiments on humans and animals have demonstrated that sympathetic innervation is inhibitory (via β-2 adrenoceptors), relatively small, slow and augmented by concurrent levels of background parasympathetic activity. These characteristics are pertinent to the sympathetic system having a specific role in our ability to adapt successfully to sustained near vision tasks and, given the clear association between near vision and the onset and development of myopia, to a putative aetiological role in myopia development in pre-disposed individuals. A fifth characteristic, namely the variation between individuals in access to an inhibitory sympathetic facility is therefore of particular interest. A novel method for continuous recording of accommodation, currently employed in a large sample longitudinal study of myopia in young adults, was used following topical instillation of non-selective (timolol) and selective (betaxolol) sympathetic β-adrenoceptor antagonists. Measures of post-task accommodative hysteresis were taken with reference to the time-course of regression of accommodation when open-loop (Difference of Gaussian) conditions were immediately imposed following short (10 s) and long (3 min) duration far (0D) and near (3D above tonic level) tasks viewed through a Badal system. Data confirm earlier informal experimental observations that only one in three individuals are likely to have access to a sympathetic inhibitory facility during sustained near vision. © 2002 The College of Optometrists.

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers

We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

Effect of β-adrenoceptor antagonists on autonomic control of ciliary smooth muscle

Purpose: Pharmacological intervention with peripheral sympathetic transmission at ciliary smooth muscle neuro-receptor junctions has been used against a background of controlled parasympathetic activity to investigate the characteristics of autonomic control of ocular accommodation. Methods: A continuously recording infrared optometer was used to measure accommodation on a group of five visually normal emmetropic subjects under open- and closed-loop conditions. A double-blind protocol between saline, timolol and betaxolol was used to differentiate between the localised action on ciliary smooth muscle and effects induced by changes in stimulus conditions. Data were collected before and 45 min following the instillation of saline, timolol or betaxolol. Open-loop post-task decay was investigated following 3 min sustained near fixation of a stimulus placed 3 D above the subject's pre-task tonic accommodation level. Closed-loop dynamic responses were recorded for each treatment condition while subjects viewed sinusoidally (0.05-0.6 Hz) or stepwise vergence-modulated targets over a 2 D range (2-4 D). Results: Open-loop data demonstrate a rapid post-task regression to pre-task tonic accommodation levels for saline and betaxolol control conditions. A slow positive post-task shift was induced by timolol indicating that sympathetic inhibition contributes to accommodative adaptation during sustained near vision. Closed-loop accommodation responses to temporally modulated sinusoidal stimuli showed characteristic features for both saline and betaxolol control conditions. Timolol induced a reduced gain for low- and mid-temporal frequencies (< 0.3 Hz) but did not affect the response at higher temporal frequencies. Response times to stepwise stimuli increased following the instillation of timolol for the near-to-far fixation condition compared with the controls and was related to the period of sustained prior fixation. Conclusions: Modulation of accommodation under open- and closed-loop conditions by a non-selective β-blocker is consistent with the temporal and inhibitory features of sympathetic innervation to ciliary smooth muscle. Although parasympathetic innervation predominates there is evidence to support a role for sympathetic innervation in the control of ocular accommodation. © 2002 The College of Optometrists.

Autonomic, biometric and oculomotor correlates of myopia in young adults

The principal work reported in this thesis is the examination of autonomic profile of ciliary muscle innervation as a risk factor in myopia development. Deficiency in sympathetic inhibitory control of accommodation has been proposed as a contributory factor in the development of late onset myopia (LOM). Complementary measurements of ocular biometry, oculomotor function and dynamic accommodation response were carried out on the same subject cohort, thus allowing cross-correlation of these factors with. autonomic profile. Subjects were undergraduate and postgraduate students of Aston University. A 2.5 year longitudinal study of refractive error progression in 40 subjects revealed the onset of LOM in 10, initially emmetropic, young adult subjects (age range 18-24 years) undertaking substantial amounts of near work. A controlled, double blind experimental protocol was conducted concurrently to measure post-task open-loop accommodative regression following distance (0 D) or near (3 D above baseline tonic accommodation) closed-loop tasks of short (10 second) or long (3 minute) duration. Closed-loop tasks consisted of observation of a high contrast Maltese cross target; open-loop conditions were imposed by observation of a 0.2 c/deg Difference of Gaussian target. Accommodation responses were recorded continuously at 42 Hz using a modified Shin-Nippon SRW-5000 open-view infra-red optometer. Blockade of the sympathetic branch of accommodative control was achieved by topical instillation of the non-selective b-adrenoceptor antagonist timolol maleate. Betaxolol hydrochloride (non-selective b1-adrenoceptor antagonist) and normal saline were employed as control agents. Retarded open-loop accommodative regression under b2 blockade following the 3 minute near task indicated the presence of sympathetic facility. Sympathetic inhibitory facility in accommodation control was found in similar proportions between LOM and stable emmetropic subjects. A cross-sectional study (N=60) of autonomic profile showed that sympathetic innervation of ciliary muscle is present in similar proportions between emmetropes, early-, and late-onset myopes. Sympathetic facility was identified in 27% of emmetropes, 21% of EOMs and 29% of LOMs.

Behavioural correlates of ocular accomodation and the autonomic nervous system

The binding issue of th is thesis was the examination of workload, induced by relinotopic and spatiotopic stimuli, on both the ocu lomotor and cardiovascular systems together with investigating the covariation between the two systems - the 'eye-heart' link. Further, the influence of refractive error on ocular accommodation and cardiovascular function was assessed. A clinical evaluation was undertaken to assess the newly available open-view infrared Shin-Nippon NVision-K 5001 optometer, its benefit being the capability to measure through pupils = 2.3 mm. Measurements of refractive error taken with the NVision-K were found to be both accurate (Difference in Mean Spherical Equivalent: 0.14 ± 0.35 D; p = 0.67) and repeatable when compared to non-cycloplegic subjective refraction. Due to technical difficulties, however, the NVision-K could not be used for the purpose of the thesis, as such, measures of accommodation were taken using the continuously recording Shin-Nippon SRW-5000 openview infrared optometer, coupled with a piezo-electric finger pulse transducer to measure pulse. Heart rate variability (HRV) was spectrally analysed to determine the systemic sympathetic and parasympathetic components of the autonomic nervous system (ANS). A large sample (n = 60), cross-sectional study showed late-onset myopes (LOMs) display less accurate responses when compared to other refractive groups at high accommodative demand levels (3 .0 0 and 4.0D). Tonic accommodation (TA) was highest in the hypermetropes, fo llowed by emmetropes and early-onset myopes while the LOM subjects demonstrated statistically significant lower levels of TA. The root-meansquare (RMS) value of the accommodative response was shown to amplify with increased levels of accommodative demand. Changes in refractive error only became significant between groups at higher demand levels (3.0 D and 4.0 D) with the LOMs showing the largest magnification in oscilIations. Examination of the stimulus-response cross-over point with the unit ratio line and TA showed a correlation between the two (r = 0.45, p = 0.001), where TA is approximately twice the dioptric value of the stimulus-response cross-over point. Investigation of the relationship between ocular accommodation and systemic ANS function demonstrated covariation between the systems. Subjects with a faster heart rate (lower heart period) tended to have a higher TA value (r = -0.27, p < 0.05). Further, an increase in accommodative demand accompanies a faster heart rate. The influence of refractive error on the cardiovascular response to changes in accommodative demand, however, was equivocal. Examination of the microfluctuations ofacconunodation demonstrated a correlation between the temporal frequency location of the accommodative high Frequency component (HFC) and the arterial pulse frequency. The correlation was present at a range of accommodative demands from 0.0 D to 4.0 D and in all four refractive groups, suggesting that the HFC was augmented by physiological factors. Examination of the effect of visual cognition on ocular accommodation and the ANS confirmed that increasing levels of cognition affect the accommodative mechanism. The accommodative response shifted away from the subject at both near and far. This shift in accommodative response accompanied a decay in the systemic parasympathetic innervation to the heart. Differences between refractive groups also existed with LOMs showing less accurate responses compared to emmetropes. This disparity, however, appeared to be augmented by the systemic sympathetic nervous system. The investigations discussed explored Ihe role of oculomotor and cardiovascular fu nction in workload enviromnents, providing evidence for a behavioural link between the cardiovascular and oculomotor systems.

Sympathetic innervation of ciliary muscle and oculomotor function in emmetropic and myopic young adults

Purpose: Evidence exists for an additional inhibitory accommodative control system mediated by the sympathetic branch of the autonomic nervous system (ANS). This work aims to show the relative prevalence of sympathetic inhibition in young emmetropic and myopic adults, and to evaluate the effect of sympathetic facility on accommodative and oculomotor function. Methods: Profiling of ciliary muscle innervation was carried out in 58 young adult subjects (30 emmetropes, 14 early onset myopes, 14 late onset myopes) by examining post-task open-loop accommodation responses, recorded continuously by a modified open-view infrared optometer. Measurements of amplitude of accommodation, tonic accommodation, accommodative lag at near, AC/A ratio, and heterophoria at distance and near were made to establish a profile of oculomotor function. Results: Evidence of sympathetic inhibitory facility in ciliary smooth muscle was observed in 27% of emmetropes, 21% of early-onset myopes and 29% of late-onset myopes. Twenty-six percent of all subjects demonstrated access to sympathetic facility. Closed-loop oculomotor function did not differ significantly between subjects with sympathetic facility, and those with sympathetic deficit. Conclusions: Emmetropic and myopic groups cannot be distinguished in terms of the relative proportions having access to sympathetic inhibition. Presence of sympathetic innervation does not have a significant effect on accommodative function under closed-loop viewing conditions. © 2005 Elsevier Ltd. All rights reserved.

Drugs and the autonomic nervous system

The nervous systems can initially be divided up into the central and peripheral nervous systems. The central nervous system is the brain and spinal cord and drugs that modify the central nervous system are considered as a subject in systematic pharmacology (therapeutics) section. Everything neural, other that the central nervous system, can be considered peripheral nervous systems. The peripheral nervous systems can be divided into the autonomic(involuntary) nervous system, which is the system that performs without your conscious help, and the somatic or voluntary nervous system, which you can consciously control(Figure 7.1). In addition the autonomic nervous system is divided into the sympathetic and parasympathetic nervous systems...