Peripheral Autonomic Pathways Research Articles

Headache and Autonomic Dysfunction: a Review.

We explore the anatomy of the central and peripheral autonomic pathways involved in primary headache as well as the mechanisms for secondary headache associated with disorders of the autonomic nervous system. The prevalence and clinical presentation of cranial and systemic autonomic symptoms in these conditions will be discussed, with a focus on recent studies. Several small studies have utilized the relationship between headache and the autonomic nervous system to identify potential biomarkers to aid in diagnosis of migraine and cluster headache. Headache in postural orthostatic tachycardia syndrome (POTS) has also been further characterized, particularly in its association with orthostatic headache and spontaneous intracranial hypotension (SIH). This review examines the pathophysiology of primary and secondary headache disorders in the context of the autonomic nervous system. Mechanisms of headache associated with systemic autonomic disorders are also reviewed.

Physiology and Pathophysiology of the Autonomic Nervous System

This article reviews the anatomic, functional, and neurochemical organization of the sympathetic and parasympathetic outputs; the effects on target organs; the central mechanisms controlling autonomic function; and the pathophysiologic basis for core symptoms of autonomic failure. Functional neuroimaging studies have elucidated the areas involved in central control of autonomic function in humans. Optogenetic and other novel approaches in animal experiments have provided new insights into the role of these areas in autonomic control across behavioral states, including stress and the sleep-wake cycle. Control of the function of the sympathetic, parasympathetic, and enteric nervous system functions depends on complex interactions at all levels of the neuraxis. Peripheral sympathetic outputs are critical for maintenance of blood pressure, thermoregulation, and response to stress. Parasympathetic reflexes control lacrimation, salivation, pupil response to light, beat-to-beat control of the heart rate, gastrointestinal motility, micturition, and erectile function. The insular cortex, anterior and midcingulate cortex, and amygdala generate autonomic responses to behaviorally relevant stimuli. Several nuclei of the hypothalamus generate coordinated patterns of autonomic responses to internal or social stressors. Several brainstem nuclei participate in integrated control of autonomic function in relationship to respiration and the sleep-wake cycle. Disorders affecting the central or peripheral autonomic pathways, or both, manifest with autonomic failure (including orthostatic hypotension, anhidrosis, gastrointestinal dysmotility, and neurogenic bladder or erectile dysfunction) or autonomic hyperactivity, primary hypertension, tachycardia, and hyperhidrosis.

Functional organization of peripheral vasomotor pathways.

In this article, we review the functional organization of the peripheral autonomic pathways regulating the vasculature. The final motor neurones in vasomotor pathways tend to be smaller than neurones in other autonomic pathways. This suggests that they have relatively smaller target territories and receive fewer pre-ganglionic inputs than non-vasomotor neurones. Nevertheless, single vasomotor neurones project to large areas of the vasculature separated by up to 7 mm. Different functional pools of vasomotor neurones project to specific segments of the vasculature, allowing for the selective neural control of resistance in vessels in proximal or distal regions of the vascular bed. In many cases, each functional pool of vasomotor neurones utilizes a characteristic combination of cotransmitters. The various pools of final motor neurones in vasomotor pathways receive convergent synaptic input from different pools of pre-ganglionic neurones, many of which also contain neuropeptides which enhance the excitability of the final motor neurones. The excitability of vasomotor neurones regulating gastrointestinal and mesenteric blood flow, also can be increased by the actions of peptides such as substance P that are released from visceral nociceptors. We propose that autonomic pathways regulating the vasculature are organized into 'vasomotor units'. Each vasomotor unit consists of a pre-ganglionic neurone, the final motor neurones it innervates, and the blood vessels that they regulate. The vasomotor units are likely to be grouped into functional pools that can be recruited as necessary to provide highly specific, graded control of blood flow both within and between vascular beds.

Role of nitric oxide in the regulation of cardiovascular autonomic control

Alteration in function of the cardiac autonomic nervous system has proved to be a powerful predictor of cardiac death or serious arrhythmia in patients with cardiac disease, yet little is known about the mechanisms by which this system is regulated. Recent evidence suggests that the gaseous molecule nitric oxide (NO) may act as an important mediator in this pathway. Histochemical staining techniques have identified neuronal populations that contain NO synthase within medullary cardio-regulatory sites and their peripheral autonomic pathways. Drugs that modulate the NO pathway (administered both systemically and into the central nervous system) cause changes in pre- and post-ganglionic sympathetic nerve activity that imply that NO serves to inhibit central sympathetic outflow. There is also evidence that NO may attenuate cardiovascular end-organ responses to sympathetic stimulation. Studies suggest that NO modulates cardiac vagal control, increasing the activity of central vagal motoneurons and, more contentiously, contributing to the bradycardic effects of vagal stimulation. NO also modulates so-called ‘indirect’ vagal inhibition of sympathetic cardiac responses. Additionally, central attenuation of baroreflex-mediated vagal control has been described. There is relatively little information available on the importance of NO in the regulation of human cardiovascular autonomic control. Further well-controlled studies are required.

Role of nitric oxide in the regulation of cardiovascular autonomic control

Alteration in function of the cardiac autonomic nervous system has proved to be a powerful predictor of cardiac death or serious arrhythmia in patients with cardiac disease, yet little is known about the mechanisms by which this system is regulated. Recent evidence suggests that the gaseous molecule nitric oxide (NO) may act as an important mediator in this pathway. Histochemical staining techniques have identified neuronal populations that contain NO synthase within medullary cardio-regulatory sites and their peripheral autonomic pathways. Drugs that modulate the NO pathway (administered both systemically and into the central nervous system) cause changes in pre- and post-ganglionic sympathetic nerve activity that imply that NO serves to inhibit central sympathetic outflow. There is also evidence that NO may attenuate cardiovascular end-organ responses to sympathetic stimulation. Studies suggest that NO modulates cardiac vagal control, increasing the activity of central vagal motoneurons and, more contentiously, contributing to the bradycardic effects of vagal stimulation. NO also modulates so-called 'indirect' vagal inhibition of sympathetic cardiac responses. Additionally, central attenuation of baroreflex-mediated vagal control has been described. There is relatively little information available on the importance of NO in the regulation of human cardiovascular autonomic control. Further well-controlled studies are required.

NITRIC OXIDE AND FIBROBLAST GROWTH FACTOR IN AUTONOMIC NERVOUS SYSTEM: SHORT- AND LONG-TERM MESSENGERS IN AUTONOMIC PATHWAY AND TARGET-ORGAN CONTROL

The freely diffusible messenger nitric oxide (NO), generated by NO synthase (NOS)-containing “nitroxergic” (NO-ergic) neurons, is unique among classical synaptic chemical transmitters because of its “non-specificity”, molecular “NO-receptors” (e.g. guanylyl cyclase, iron complexes, nitrosylated proteins or DNA) in target cells, intracellular targeting, regulated biosynthesis, and growth factor/cytokine-dependence. In the nervous system, expression of NOS is particularly intriguing in central and peripheral autonomic pathways and their targets. Here, anatomical and functional links appear to exist between NOS, its associated catalytic NADPH-diaphorase enzyme activity (NOSaD) and fibroblast growth factor-2 (FGF-2), a pleiotropic cytokine with mitogenic actions, suggesting mutual “short- and long-term” actions. Several recent studies performed in the rat sympathoadrenal system, an anatomically and neurochemically well-defined autonomic pathway with target-specific functional units of sympathetic preganglionic neurons (SPNs) in the spinal cord, provide evidence for this hypothesis. The NO and cytokine signals may interact at the level of gene expression, transcription factors, post-transcriptional control or second messenger cross-talk. Thus, unique biological roles of FGF-2 and the NO system are likely to exist in neuroendocrine actions, vasomotory perfusion control as well as in neurotrophic actions in sympathetic innervation of the adrenal gland. In view of their anatomical co-existence, functional interplay and synchronizing effects on neuronal networks, multiple roles are suggested for both “short- and long-term” signalling molecules in neuroendocrine functions and integrated autonomic target organ control. © 1997 Elsevier Science Ltd. All Rights Reserved.

Retrograde axonal transport of horseradish peroxidase in peripheral autonomic nerves.

An exogeneous marker protein, horseradish peroxidase (HRP) was used to race peripheral autonomic pathways in adult guinea pigs and cats. Small doses of HRP were injected into various organs and after a brief survival period, HRP activity appeared in the perikarya of autonomic neurons that supplied each injection site. After injection of HRP into the anterior chamber of the eye, reaction product was detected in the postganglionic sympathetic neurons of the superior cervical sympathetic ganglion. In another experiment, HRP reaction product was found in the cell bodies of the preganglionic sympathetic neurons that supply the adrenal medulla. These were located in the lateral gray column of the spinal cord at T6 and T7 segmental levels. Reaction product appeared in intramural postganglionic parasympathetic neurons close to an injection site in the wall of the urinary bladder and in a similiar situation in Meissner's ganglia of the ileum. Following injection into the walls of the stomach and ileum, HRP labelled cells were detected in the nodose ganglion of the vagus and in preganglionic parasympathetic neurons in the dorsal motor nucleus of this nerve. After injection into the subepicardial tissue of the heart, reaction product appeared in the stellate ganglion and also in an upper thoracic dorsal root ganglion. These data suggest that HRP is taken up by peripheral autonomic nerves of all types, and then undergoes rapid retrograde axonal transport to the perikaryon. It appears, therefore, that HRP may be useful in tracing both motor and sensory peripheral autonomic pathways.

Peripheral autonomic influence on the motility of the urinary bladder in the cat. II. "Tone".

AbstractThe micturition act was found to be regulated by an antagonistic nervous influence mediated through the two peripheral autonomic pathways to the bladder. The alterations of micturition following section and stimulation of these nerves were recorded by means of a technique (Gjone and Setekleiv 1963, Gjone 1965a, b) which does not interfere with the emptying function of the bladder. By section of the parasympathetic vesical supply the micturition reflex was abolished, whereas micturition was induced by parasympathetic stimulation. In accordance with the results of previous workers, excitatory effects on micturition were thus found to be mediated by this pathway. Following primary section of the sympathetic nerves the micturition threshold was markedly reduced, and by sympathetic stimulation interruption of reflex micturition ensued. By the latter effect, not previously demonstrated, the inhibitory influence of the sympathetic nerves to the bladder, was established. The activity of the so called“internal sphincter” was studied through direct cystoscopic examination as well as by pressure recording from the outlet region. It was concluded that the smooth muscle surrounding the internal urethral orifice acts in phase with and as part of the detrusor musculature, viz., the closure of the bladder outlet is due to relaxation, and its opening is caused by contraction. In support of this view it was noted that urinary continence persisted when the musculature of 1 he bladder neck was divided by a vertical incision, whereas incomplete and prolonged emptying of the bladder ensued subsequent to this procedure.