Annals of Otology,Rhinology & Laryngology

The distribution and role of neurotransmitters and neuromodulators in laryngeal innervation are reviewed, and our recent findings regarding the nitrergic innervation of the larynx are demonstrated for the better understanding of the complexity of the laryngeal innervation system. Noradrenergic innervation of the larynx was studied with fluorescence histochemistry and electron microscopy after application of 5-hydroxydopamine. These studies confirmed the existence of noradrenergic innervation for the submucosal glands and blood vessels, and the origin and course of noradrenergic nerve fibers contained in the laryngeal nerves and their destinations in the larynx. Cholinergic innervation of the larynx has not been clarified in detail. Many kinds of neuropeptides have been demonstrated to be involved in laryngeal innervation. Vasoactive intestinal polypeptide originating from intralaryngeal ganglionic neurons participates in laryngeal vasodilation and reduction of laryngeal seromucous secretion. Neuropeptide Y nerve fibers are few in the larynx, and most originate from the superior cervical ganglion. They are distributed around the large or medium-sized blood vessels, especially arteries. They are also associated with excretory structures. Substance P was the first neuropeptide found to be a sensory neurotransmitter in the laryngeal afferent system. It is also involved in regulation of laryngeal blood flow and secretion. Calcitonin gene—related peptide is associated with the sensory, autonomic, and motor innervation of the larynx. The majority of enkephalin nerve fibers are located close to excretory structures, although no information on the physiological significance of enkephalin is available. In addition to the above neuropeptides, the peptides histidine isoleucine, histidine methionine, and helospectin have been shown to exist in the larynx. The nitrergic innervation of the larynx has been recently studied with NADPH-diaphorase histochemistry and immunohistochemistry using antiserum against nitric oxide synthase. Nitric oxide originates from the neurons in the intralaryngeal ganglia and is believed to modulate blood flow and secretion of the larynx. It controls the laryngeal exocrine secretion in cooperation with intrinsic vasoactive intestinal polypeptide and/or extrinsic calcitonin gene—related peptide. Nitric oxide from the nodose ganglion may modulate nociception of the larynx. The existence of nitrergic neurons located in the intrinsic laryngeal muscles has been demonstrated. Many of them are bipolar or pseudounipolar, so they might be sensory in nature. The effect of injury of the recurrent laryngeal nerve on the induction of nitric oxide synthase in the laryngeal motoneurons is also discussed.

In order to characterize the brain stem circuitry that produces vocalization, the activities of brain stem respiratory neurons were recorded extracellularly during vocalization induced by electrical stimulation of the periaqueductal gray in decerebrate cats. After the onset of stimulation, the respiratory rhythm ceases, and a preparatory inspiration is induced. Following this initial inspiration, vocalization characterized by increased activities of the intrinsic laryngeal adductor and the major expiratory muscles is induced. During vocalization, most of the dorsal respiratory group inspiratory neurons increase their firing rates in phase with an increase of diaphragm activity. Inspiratory neurons with a continuous discharge pattern in the rostral ventral respiratory group increase their firing rates to augment intrinsic laryngeal abductor motoneurons and bulbospinal inspiratory neurons in the dorsal respiratory group. On the other hand, most of the bulbospinal augmenting expiratory neurons in the Bötzinger complex cease firing just after the onset of periaqueductal gray stimulation for the remainder of the stimulation period. These results indicate that at least some part of the coordinated activations of intrinsic laryngeal and respiratory muscles during vocalization are mediated via the central respiratory neurons that produce breathing.