Pathophysiology of itching and sneezing in allergic rhinitis.

Itching and sneezing represent two of the main bothersome symptoms, apart from nasal obstruction and rhinorrhea in allergic rhinitis. Apparently, activation of the central and peripheral nervous system plays a major role in the pathophysiology of this process. Sensory nerves of the afferent trigeminal system including myelinated Adelta-fibres and thin, non-myelinated C-fibres of the nasal mucosa transmit signals generating sensations, including itching and motor reflexes, such as sneezing. These nerves can be stimulated by products of allergic reactions and by external physical and chemical irritants. Via axon reflex inflammatory neuropeptides including the tachykinins substance P (SP) and neurokinin A (NKA) and the calcitonin gene related peptide are released, leading to vasodilatation, increased vascular permeability (concept of "neurogenic inflammation"), glandular activation, leukocyte recruitment and differentiation of immune cells including mast cells, eosinophils, lymphocytes and macrophages. The present paper describes nasal (micro-) anatomy and innervation and explains the central and peripheral mechanisms initiating itching and sneezing in allergic rhinitis. Further, the role of neuropeptides and neurotrophins with regard to neuronal and immune cell activation which might play a key role in the future treatment of allergic rhinitis are discussed.