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The role of the nervous system in rhinitis

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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.

Section snippets

Sensory nerves

The sensory nerves of the nose arise from the olfactory nerve, as well as from the ophthalmic (through the ethmoidal nerve) and maxillary branches of the trigeminal nerve.1, 2, 3 Nonolfactory sensory nerves consist of both myelinated and unmyelinated fibers. Unmyelinated fibers are slow conducting and, in the vast majority, belong to the nociceptor, C-fiber type. Myelinated fibers are of larger diameter and have faster nerve conduction velocity, and their function has not been fully elucidated.

Nasal symptoms and the nervous system

Fig 1 schematically depicts how nasal symptoms can be produced by neural mechanisms. Exogenous stimuli of various natures (physical or chemical), as well as endogenous biochemical products, can activate sensory nerve endings that are in abundance in the nasal mucosa, interdigitating between epithelial cells. Action potentials are transmitted to the cell bodies of the trigeminal ganglion and further into the midbrain, where secondary synapses eventually lead to the generation of central reflex

Neural hyperresponsiveness in allergic rhinitis

The fact that typical symptoms of rhinitis can be produced through neural mechanisms in the absence of any obvious abnormality in the nasal mucosa indicates that these symptoms are part of the normal function of the respiratory system. Teleologically, they provide primary defenses against external danger signals, whether physical or chemical. The question is why these symptoms are exaggerated in the case of allergic rhinitis. As discussed above, an obvious answer is that the products of

Does nonallergic rhinitis represent a state of neural hyperresponsiveness?

Nonallergic rhinitis consists of a variety of syndromes that are only to some extent distinguishable based on clinical and, in some cases, laboratory characteristics.126, 127 A large subgroup of patients with nonallergic rhinitis have nasal symptoms in the absence of any inflammatory changes in the nasal mucosa or any evidence of an infectious, systemic, or metabolic process. Several terms have been used to describe this group of patients, including nonallergic, noninfectious rhinitis;

Mechanisms of neural hyperresponsiveness in the nose

The mechanisms through which the nervous system can undergo changes that manifest with the hyperresponsiveness phenotype are steadily being unveiled, primarily in animal models.149, 150, 151, 152 Changes in neuronal function can occur at various levels, from sensory nerve endings to sensory ganglia, the central nervous system, autonomic ganglia, or the postganglionic-effector cell junctions. Most of these changes are associated with local inflammatory events, but the mechanisms might differ

The nerves of the nose as a conduit for systemic interactions

Every aspect of the function of the nose, from olfaction to air conditioning to airborne particle trapping, is associated with defensive and homeostatic mechanisms of the body. This widespread and demanding operation has to rely on an effective and fast communication system, through which danger signals can be transmitted to specific response centers. The systemic circulation can certainly play a part in this role; however, the reaction time and the specificity of circulatory signals do not

Conclusions

Chronic rhinitis in its various forms is an extremely common problem. Despite the availability of several forms of treatment, a substantial number of patients with rhinitis are not satisfied with the outcomes and seek additional medical care. To improve our therapeutic modalities, we need to further our understanding of the pathophysiology of rhinitis, both of allergic and nonallergic origin. A central approach toward this goal is to understand how symptoms are generated and what makes a

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    (Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)

    Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MD

    Disclosure of potential conflict of interest: A. Togias has consultant arrangements with AirPharma, Altana, Genentech, GlaxoSmithKline, MedPointe, Merck, and Novartis and is on the speakers' bureau for Genentech, Merck, and Novartis. A. Sanico has consultant arrangements with Merck and AstraZeneca; has received grant support from NIH K23, Merck, and Alcon; and is on the speakers' bureau for Merck, Pfizer, UCB, GlaxoSmithKline, and Aventis. The rest of the authors have declared that they have no conflict of interest.

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