Distinct modulation of tracheal and laryngopharyngeal cough via superior laryngeal nerve in cat
Introduction
Superior laryngeal nerve (SLN), a branch of the vagus nerve, innervates laryngeal musculature and mucosa. As such, SLN is significantly involved in vocalization, respiration, swallowing and coughing (Paraskevas et al., 2012; Cha et al., 2017). The SLN bifurcates into the internal branch, which conveys afferent fibers from the laryngeal mucosa, and the external branch, which provides the only efferent fibers to the cricothyroid muscle participating in meticulous control of the voice (Sakorafas et al., 2012; Cha et al., 2017). Animal studies showed that the types of reflex response to stimulation of airway mucosa vary with the site of stimulation (Widdicombe, 1954; Nishino et al., 1996) and also species (Korpas and Tomori, 1979; Tatar et al., 1994). Apnea inducable from the larynx represents respiratory arrest, expiration reflex (typical by a short strong expiratory effort) is produced by brief single touch of the glottis. Swallow, capable of removing material from the pharyngeal region “downwards “to the stomach is characterized by coordinated sequence of activity of pharyngeal, laryngeal and esophageal muscles including contraction of cricopharyngeus (upper esophageal sphincter) and inspiratory muscles, e.g. the diaphragm, producing “swallow breath “(Pitts et al., 2013). Intact complete swallow is generetad by afferent signals conducted by several nerves from the area including pharyngeal and esophageal branches of the vagus nerve and SLN, although swallow can also be produced experimentally by electrical stimuli exclusively to the SLN (Dick et al., 1993; King et al., 2020; Umezaki et al., 2020). SLN stimulation in rodents that are no able to cough e.g. rat is exclusively triggers swallowing and is use to decipher the central mediation of swallowing (Hashimoto et al., 2019; Fuse et al., 2020) Cough, the main cleaner of the respiratory tract, being coordinated sequence of powerfull inspiration and expiration is inducable from all laryngeal (up to pharyngeal) area, through all trachea to the large bronchi (Widdicombe, 1954; Korpas and Tomori, 1979; Tatar et al., 1994).
The differences in reflex responses from different sites of larynx may be explained by an uneven distribution of airway receptors responsible for the reflex response (Nishino et al., 1996). Sensory deficit in the area of the larynx correlates with the occurrence of swallowing dysfunction and the development of aspiration pneumonia (Ding et al., 1993). On the other hand, percutaneous SLN block is an effective treatment for neurogenic cough (Simpson et al., 2018).
Cooling or a section of the nerve (e.g. vagotomy) represents an experimental technique, which can partially or completely abolish coughing (Klassen et al., 1951; Widdicombe, 1954; Adams et al., 1987; Tatar et al., 1994; Canning et al., 2004). Irrespective of the number and type of receptors engaged, the action potential initiation and propagation in afferent nerves depends on activation of a limited number of voltage-gated sodium channel subtypes (Brozmanova et al., 2019; Bennett et al., 2019), which are temperature dependent (Collins and Rojas, 1982; Sarria et al., 2012). Cooling of the related nerve can simulate a production of the cough reflex with lower excitability (less afferent drive), but without direct suppression of cough receptor activity as their response to mechanical touch was not altered. A section of the nerve represents a model of total interruption of the nerve conduction including primary drive as well as afferent feedback (Simera et al., 2016).
Considering the differences in the anatomy and afferent innervation of the larynx and the lower airways as well as the hypothesis that the laryngopharyngeal cough reflex might be qualitatively different from cough elicited from the lower airways, we attempted to determine the effects of unilateral and bilateral cooling (< 5 °C) and the bilateral transsection of the SLN on mechanically induced tracheobronchial and laryngopharyngeal cough in anaesthetized cats. We expected to find more pronounced changes in the laryngopharyngeal cough response including alterations in temporal characteristics of the reflex.
Section snippets
Experimental protocol
All procedures were performed in accordance with the laws, rules, and regulations of the Slovak Republic and with the Directive 2010/63/EU of the European Parliament. Protocols were approved by the Ethics Committee of Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava. Experiments were performed on 12 spontaneously breathing cats (3 females and 9 males; 4.19 ± 0.23 kg) anesthetized with sodium pentobarbital (Pfannenschmidt GmbH; initial dose 38 mg/kg, i.p., 1−3 mg/kg
Spatio-temporal analysis data
Mechanical stimulation of the tracheobronchial mucosa resulted in repetitive coughing (12.7 ± 2.5 TB per 10 s stimulation in control for bilateral cooling, 9 cats; Fig. 1A). The single stimulus to the laryngopharyngeal mucosa resulted in LPh (1.26 ± 0.31 LPh per stimulus in control for bilateral cooling, 7 cats; Fig. 2A, Table 1). We analyzed 420 TB and 49 LPh in control, 286 TB and 25 LPh during unilateral SLN cooling, 143 TB and 13 LPh during bilateral SLN cooling, 121 TB before and 100 TB
Discussion
The main finding of our study in anesthetized cats is that laryngopharyngeal cough significantly, but not exclusively, depends on the intact afferent drive via SLN, while tracheobronchial cough has no modulation via this nerve.
The SLN conducts afferent, efferent and feedback impulses from/to the laryngeal musculature and mucosa and has a key role in vocalization, respiration, and crucial glottic reflexes associated with deglutition, coughing, and vomiting (Paraskevas et al., 2012; Cha et al.,
Acknowledgements
This work was supported by grants VEGA1/0275/19; VEGA1/0092/20.
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