Vagal neuropathy:
Cough reflex hypersensitivity is manifested by the occurrence of coughing attacks, often triggered by low-threshold stimuli to which the patient is exposed during normal daily activities. Cough reflex hypersensitivity is observed in all respiratory diseases (acute or chronic) when cough is a predominant feature. At the same time, neuroinflammation is one of the most important causes of cough reflex hypersensitivity (17). Cranial nerves, including the vagus nerve, may be affected by inflammatory neuropathic processes. The vagus nerve extensively innervates the respiratory and digestive tracts. Dysfunction of the vagus nerve can cause cough (18).
Chronic neuropathy of the laryngopharyngeal nerve, which is a branch of the vagus nerve, manifests as symptoms of laryngeal irritation such as chronic cough, stridor, pharyngeal irritation, dysphonia, and foreign body sensation in the throat. In patients suffering from laryngeal neuropathy, there is increased sensitization of the cough reflex with abnormal neuropathic responses to receptor stimuli. Laryngopharyngeal neuropathy can lead to alterations in the afferent branches of the laryngeal and digestive reflex arcs. Consequently, various stimuli such as acids may trigger the symptoms. This may be accompanied by paradoxical vocal fold movements as part of a syndrome of irritated larynx, in which hypersensitivity of afferent reflexes is a common mechanism (19). Neuropathy of the vagus nerve may also affect other motor branches of the vagus nerve and cause paresis or paralysis of the vocal folds, paradoxical vocal fold movements, or other sensory branches causing chronic cough and other symptoms such as scratchy throat, sore throat, laryngeal paresthesias, and laryngospasm. These symptoms can be aggravated and provoked by talking, laughing, irritating inhalants, and palpation of the larynx (20).
Vagus nerve dysfunction may occur after viral infections or exposure to irritants or may be caused by chronic diseases such as asthma. In asthma, increased levels of substance P and neurokinin A in induced sputum samples are indicative of neuronal activation of the airways. Besides, levels of the neuropeptide calcitonin gene-related peptide (NCRP) in bronchoalveolar lavage from children with chronic cough are positively correlated with capsaicin cough reflex sensitivity. There is increased expression of NCRP in the nerves supplying the airways in patients with chronic cough (21). In diseases associated with persistent coughs, such as idiopathic pulmonary fibrosis, there are high levels of nerve growth factor in the airways of patients, which has important neuroinflammatory consequences and maybe one of the factors responsible for the chronicity of cough (22). Vitamin B12 deficiency can cause sensory neuropathy leading to dysfunction of the pharynx and larynx, which can trigger a chronic cough. Vitamin B12 supplementation can improve histamine threshold and significantly increase cough threshold in patients with chronic cough due to vitamin B12 deficiency but has no significant effect on individuals without deficiency (23). Vitamin B12 deficiency-related cough should be kept in mind in patients treated with proton pump inhibitors or cytotoxic drugs. Considering chronic cough as a neuropathic disorder, just like neuropathic chronic pain, will significantly change the possible strategies for the diagnosis and management of chronic cough (24).
Neurological Conditions Associated with Diminished Cough Reflex Sensitivity:
Because it is a reflex that predominantly involves the brainstem and is modulated by the cerebral cortex, the cough may be diminished in various neurologic disorders affecting both the peripheral and central nervous systems. A diminished cough reflex (dystonia) is associated with a high risk of developing pneumonia and an increased rate of morbidity and mortality in these disorders.