[Neural control of the respiratory nasal mucosa].
Knipping S,Riederer A,Berghaus A
HNO
Respiratory nasal mucosa fulfils the function of pretreating the inspired air. The periodic nasal cycle and pathologic functional disturbances of the endonasal tissue influence the nasal passages. The secretion of the seromucous glands and extravasation from the blood vessels are essential for mucocilliary transport. These physiological mechanisms are partially controlled by neural regulation. Besides classic neurotransmitter neuropeptides such as VIP, CGRP, SP and NPY, nitric oxide also shares this role. A network of sensory, sympathetic and parasympathetic nerve fibres protects the respiratory mucous membranes from external and internal irritation. In addition, blood vessels and glands are influenced by endothelial and humoral factors. For the different types of rhinitis, sensory neuropeptides and inflammatory mediators take part in the pathomechanisms and can lead to a so called neurogenic inflammation of the nasal mucosa.
10.1007/s00106-004-1061-9
[Immunohistochemical study of the neuroanatomy of the nasal turbinate in man. Innervation pattern of the blood vessels].
Riederer A,Knipping S,Fischer A,Grevers G,Zietz C
Laryngo- rhino- otologie
The complex vasculature of the human nasal mucosa plays an important role in the protection of the lower respiratory airways. It has to react to different external and internal stimuli and is under control of the autonomic nervous system. The aim of our study was to detect the precise localisation of neural structures in human nasal mucosa vessels under physiological conditions. Silver impregnation and histochemical staining techniques only allowed a partial aspect of autonomic innervation. Modern immunostaining methods with antibodies to neuron-specific enolase (NSE) and S-100 protein proved to be better for the demonstration of nerve structures. Tissue samples were taken from inferior turbinates received at mucotomy in 42 patients. After fixation the samples were embedded in paraffin wax and cut into serial sections. Additionally frozen sections were performed. The immunocomplexes were visualised by the avidin-biotin-complex (ABC) or by the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. A high density of S-100 and NSE immunoreactivity of neuronal and glial components of autonomic innervation could be demonstrated in the vessels of human nasal turbinates. Branching off relatively thick nerve bundles of the lamina propria fibres extended to the adventitia of the arteries near the periost and formed a periarterial nerve plexus. Fibres of this plexus supplied the smooth muscle tissue of the tunica media. Around veins only a few single nerve fibres could be demonstrated. By using immunocytochemical techniques it is possible to correlate the localisation of the classical neurotransmitters and multiple vasoactive neuropeptides with the corresponding innervation structures of the complex vasculature in human nasal mucosa.
10.1055/s-2007-997080
[Electron microscopy studies of vascular innervation of nasal mucosa in the human].
Riederer A,Grevers G,Welsch U,Herzmann S
Laryngo- rhino- otologie
BACKGROUND:The distribution of neural structures in human nasal vasculature is still not completely understood. To date, immunocytochemical and histochemical studies of the innervation pattern and neurotransmitter distribution have only been performed using light microscopy. The aim of this study was to verify these results by electron microscopy and to obtain new knowledge of the innervation of the individual vessel types. The target was to determine the role of the different vessels in the swelling mechanism in human nasal mucosa. MATERIAL AND METHODS:Specimens were prefixed in glutaraldehyde and postfixed in osmium tetroxide. After dehydration they were embedded in araldite. Ultrathin sections were cut, contrasted with uranylacetate and lead citrate, and studied under EM. RESULTS:Nasal vasculature is controlled by a dense innervation. Amyelinated longitudinal nerve bundles and smaller axon conglomerates are detected in the arterial adventitia. Capacitance vessels (veins) in general show few nerve structures, which, in contrast to arteries, are also located between the smooth muscle cells. Cushion veins, however, reveal a stronger innervation pattern especially in their muscular swelling. In contrast to smaller arterioles, no axons can de demonstrated in capillaries. CONCLUSION:The density of innervation in arteries and cushion veins seems to indicate that these vessel types are the central neural control point for the swelling mechanism in human nasal mucosa. Capillary function, however, does not seem to be directly influenced by the autonomic nervous system.
10.1055/s-2007-997452
Effect of postural change on nasal airway and autonomic nervous system established by rhinomanometry and heart rate variability analysis.
Ko Jen-Hung,Kuo Terry B J,Lee Guo-She
American journal of rhinology
BACKGROUND:Clinically, nasal obstruction is experienced frequently in the supine position, and the nasal autonomic nervous system (ANS) may be involved in the mechanism. The central ANS functions at maintaining cardiovascular hemodynamics. However, during postural change, the corresponding changes of the central ANS may simultaneously change the nasal airway as well. In this study, the relationships between nasal ANS and central ANS were explored using rhinomanometry (RMM) and heart rate variability (HRV) analysis between postural changes. METHODS:Twelve healthy volunteers aged between 19 and 39 years and without a history of allergic rhinitis or significant nasal anatomic obstruction were enrolled for the study. The nasal airway was measured using RMM in a sitting position and then in a supine position; the electrocardiography was simultaneously recorded. RESULTS:In supine position, the total nasal airflow significantly decreased and the airway resistance significantly increased (p<0.05, Wilcoxon signed-rank test). The ratio of low frequency power to high frequency (HF) power of HRV that represents sympathetic modulation significantly decreased in the supine position (p<0.05, Wilcoxon signed-rank test). However, the HF that represents parasympathetic activity did not show significant change with postural change. The correlations of heartbeat interval with total inspiratory airflow and total inspiratory resistance were significant also (p<0.01, Pearson's correlation). CONCLUSION:The central ANS activities significantly correlated with changes to the nasal airway during postural change. The central ANS, especially the sympathetic nervous system, may play a role in controlling nasal airway during postural change.
10.2500/ajr.2008.22.3143
Rhinitis and sleep disorders: The trigeminocardiac reflex link?
Bindu Barkha,Singh Gyaninder Pal,Chowdhury Tumul,Schaller Bernhard
Medical hypotheses
Rhinitis, allergic or non-allergic, is an inflammatory condition of the nose. It is associated with a wide range of sleep disorders that are generally attributed to nasal congestion and presence of inflammatory mediators like cytokines and interleukins. However, the pathophysiological mechanisms behind these sleep disorders remain unclear. On the other hand, the trigeminocardiac reflex (TCR) has recently been linked to various sleep disorders like obstructive sleep apnea, sleep bruxism and rapid eye movement (REM) sleep apnea. TCR can be incited by stimulation of the trigeminal nerve or the area innervated by its branches including the nasal mucosa. Trigeminal nasal afferents can be activated on exposure to noxious stimuli (mechanical or chemical) like ammonia vapors, carbon-dioxide, nicotine, hypertonic saline, air-puffs and smoke. In rhinitis, there is associated neuronal hyper-responsiveness of sensory nasal afferents due to inflammation (which can be suppressed by steroids). This may further lead to increased occurrence of TCR in rhinitis. Moreover, there is involvement of autonomic nervous system both in rhinitis and TCR. In TCR, parasympathetic over activity and sympathetic inhibition leads to sudden onset bradycardia, hypotension, apnea and gastric motility. Also, the autonomic imbalance reportedly plays a significant role in the pathophysiology of rhinitis. Thus, considering these facts we hypothesize that the TCR could be the link between rhinitis and sleep disorders and we believe that further research in this direction may yield significant development in our understanding of sleep disorders in rhinitis.
10.1016/j.mehy.2017.04.019
Role of the autonomic nervous system in the development of cardiovascular changes during nasal apnoea and lung inflation.
Javorka K,Tomori Z
Physiologia Bohemoslovaca
The role of the sympathetic system in the development of bradycardia during nasal apnoea and the role of the sympathetic and parasympathetic system in the development of cardiovascular changes during and immediately after lung inflation were determined in anaesthetized rabbits. Transection of the cervical cord (C5-7) completely blocked the hypertensive response to chemical stimulation of the nasal mucosa. The degree of nasal bradycardia was 72% lower than in stimulation of the controls. Propranolol had no effect on the hypertensive reaction, but inhibited nasal bradycardia, which was 68% lower than in the controls. Lung inflation induced tachycardia, which was only non-significantly reduced by bilateral vagotomy. Vagotomy inhibited the bradycardiac response to removal of occlusion of the trachea and the subsequent rise in blood pressure, however. Cervical cord transection likewise did not reduce inflation-induced tachycardia, but it significantly influenced the heart rate during the second phase of prolonged inflation, when the heart is affected by hypoxia. Inflation-induced tachycardia was likewise not influenced by bilateral vagotomy associated with cervical cord transection. Similar cardiac responses also occur in the presence of the simple increase in pericardial pressure produced by left pneumothorax without lung inflation.
Neurology of allergic inflammation and rhinitis.
Canning Brendan J
Current allergy and asthma reports
Afferent nerves, derived from the trigeminal ganglion, and postganglionic autonomic nerves, derived from sympathetic and parasympathetic ganglia expressing many different neurotransmitters, innervate the nose. Reflexes that serve to optimize the air-conditioning function of the nose by altering sinus blood flow, or serve to protect the nasal mucosal surface by mucus secretion, vasodilatation, and sneezing, can be initiated by a variety of stimuli, including allergen, cold air, and chemical irritation. Activation of nasal afferent nerves can also have profound effects on respiration, heart rate, blood pressure, and airway caliber (the diving response). Dysregulation of the nerves in the nose plays an integral role in the pathogenesis of allergic rhinitis. Axon reflexes can precipitate inflammatory responses in the nose, resulting in plasma extravasation and inflammatory cell recruitment, while allergic inflammation can produce neuronal hyper-responsiveness. Targeting the neuronal dysregulation in the nose may be beneficial in treating upper airway disease.
10.1007/s11882-002-0021-2
Autonomic function and dysfunction of the nose and sinuses.
Loehrl Todd A
Otolaryngologic clinics of North America
Patients with inflammatory disorders of the upper airway exhibit varying degrees of ANS dysfunction, including the sympathetic, parasympathetic,and sensory components. Current evidence is insufficient with regard to the exact role of ANS dysfunction and its relationship to these disorders.Thus, the interaction of the ANS and sinonasal inflammation deserves further study.
10.1016/j.otc.2005.08.004
Nasal 'pressure' receptors.
Tsubone H
Nihon juigaku zasshi. The Japanese journal of veterinary science
This study was performed to identify, recording from single fibers of the ethmoidal nerve, nasal receptors which respond to changes in the upper airway pressure during nasal occlusion. In 15 anaesthetized rats breathing through the nose, three consecutive nasal occlusions were performed while recording the afferent activity of ethmoidal nerve fibers, the EMG activity of an external intercostal muscle, temperature in the nose and upper airway pressure. Twenty-two afferent fibers were activated during the three inspiratory efforts with occlusions applied at end-expiration, when the upper airway was subjected to negative pressure (-1.93, -2.16 and -2.22 kPa at the 1st, 2nd and 3rd effort, respectively). The number of impulses was 24, 22 and 20 (n = 22) at the 1st, 2nd and 3rd effort, respectively. The pressure threshold were measured as -0.73, -0.87 and -0.96 kPa (n = 22) in each effort. Three fibers were also stimulated by positive pressure during occlusions performed at end-inspiration. In 5 rats breathing through a tracheostomy, maintained negative (-0.1-3.7 kPa) and positive (0.8-3.0 kPa) pressures were applied to the isolated upper airway. All the 12 fibers tested were activated by the maintained negative pressure, whereas three of them were also activated by the maintained positive pressure. However, none of fibers tested were stimulated by tracheal occlusions. These results indicate that the ethmoidal branch of the trigeminal nerve contains fibers connected to nasal 'pressure' receptors, mostly 'negative pressure' receptors, that may play a role in the maintenance of upper airway patency.
Neuroregulation of the nose and bronchi.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
The vascular beds, submucosal glands, and airway vasculature are the three primary effector tissues in the airways, and all are under the control of the parasympathetic (vagal) and sympathetic nervous systems. Parasympathetic nerves play a more important role in smooth muscle contraction and gland secretion. The complex neurogenic mechanisms initiated by activation of sensory nerves have been clarified to a large extent by studies on experimental animals. For example, inflammation or an allergic response will cause neurogenic inflammation due to axon reflexes; central nervous reflexes will modulate activity in all of the effector tissues; and these reflex responses will be modulated by local reflexes via parasympathetic ganglia. Similar mechanisms are suspected in humans, but their importance still needs to be fully established.
10.1111/j.1365-2222.1996.tb00656.x
Vasomotor rhinitis update.
Lal Devyani,Corey Jacquelynne P
Current opinion in otolaryngology & head and neck surgery
PURPOSE OF REVIEW:This review was conducted to examine new data on vasomotor rhinitis, a common clinical problem. RECENT FINDINGS:Recent publications highlight advances in the study of the pathophysiology of vasomotor rhinitis. Electron microscopic and ultracytochemical evaluation of the nasal mucosa in vasomotor rhinitis demonstrates an emerging role of neuropeptides and nitric oxide in the pathogenesis of vasomotor rhinitis. Ozone, cigarette smoke, and other environmental factors may trigger neurogenic mechanisms that lead to vasomotor rhinitis. Objective tests have documented the presence of hypoactive sympathetic autonomic dysfunction. Such assessments also suggest autonomic dysfunction as a possible link between vasomotor rhinitis and gastroesophageal reflux disease. Recent publications propose nasal secretory protein analysis as a possible diagnostic tool. Evidence-based review of treatment outcomes shows topical sprays of azelastine, budesonide, and ipratropium to be of benefit in vasomotor rhinitis. SUMMARY:A better understanding of the role of nitric oxide and neuropeptides in the pathogenesis of vasomotor rhinitis has opened new avenues in research, diagnosis, and management. Clinical diagnosis may be aided by the analysis of nasal secretory proteins. Effective treatments include antihistamine, anticholinergics, and steroid nasal sprays.
10.1097/01.moo.0000122310.13359.79
The role of the autonomic nerves in the control of nasal circulation.
Lung M A
Biological signals
Patients suffering from allergic or vasomotor rhinitis usually show nasal mucosal hyperaemia, engorgement, hyperrhinorrhoea and obstruction of the nasal airway. The nasal mucosa is drained by two venous systems which are anatomically and functionally separate. The nasal mucosa receives tone discharges from the sympathetic nerves but not from the parasympathetic nerves. Sympathetic nerve stimulation causes constriction of the resistance vessels via the alpha-adrenergic mechanism and constriction of the capacitance vessels via the alpha-adrenergic mechanism and some non-adrenergic and non-cholinergic mechanism; the capacitance vessels are under more prominent sympathetic influence than the resistance vessels. Parasympathetic nerve stimulation causes non-cholinergic dilatation of both resistance and capacitance vessels; dilatation is more pronounced in the posterior venous system. Simultaneous optimal stimulation of the autonomic nerves resulted in vasoconstriction, especially of the capacitance vessels. Hence, nasal congestion may be related more to a withdrawal of sympathetic discharge than to an overactivity of the parasympathetic nerves.
10.1159/000109439
The role of the nervous system in rhinitis.
Sarin Seema,Undem Bradley,Sanico Alvin,Togias Alkis
The Journal of allergy and clinical immunology
The nose provides defensive and homeostatic functions requiring rapid responses to physical and chemical stimuli. As a result, it is armed with a complex nervous system that includes sensory, parasympathetic, and sympathetic nerves. Sensory nerves transmit signals from the mucosa, generating sensations, such as pruritus; motor reflexes, such as sneezing; and parasympathetic and sympathetic reflexes that affect the glandular and vascular nasal apparatuses. Reflexes directed to the nose are also generated by inputs from other body regions. Hence all symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways. In addition, neural signals generated in the nose can influence distal physiology, such as that of the bronchial tree and the cardiovascular system. Neural function can be chronically upregulated in the presence of mucosal inflammation, acutely with an allergic reaction, or even in the absence of inflammation, as in cases of nonallergic rhinitis. Upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation, a phenomenon that depends on the release of neuropeptides on antidromic stimulation of nociceptive sensory nerves. The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to be playing a role. Neurotrophins, such as the nerve growth factor, are prime candidates as mediators of neural hyperresponsiveness. The many interactions between the nervous and immune systems contribute to nasal physiology but also to nasal disease.
10.1016/j.jaci.2006.09.013
The Body, the Brain, the Environment, and Parkinson's Disease.
Journal of Parkinson's disease
The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson's disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson's disease and open the door toward the ultimate goal -prevention.
10.3233/JPD-240019