Microinjection of DLH into the region of the caudal ventral respiratory column in the cat: evidence for an endogenous cough-suppressant mechanism

Abstract

Poliacek I, Wen-Chi Corrie L, Wang C, Rose MJ, Bolser DC. Microinjection of DLH into the region of the caudal ventral respiratory column in the cat: evidence for an endogenous cough-suppressant mechanism. J Appl Physiol 102: 1014 -1021, 2007. First published November 30, 2006; doi:10.1152/japplphysiol.00616.2006.-The caudal ventral respiratory column (cVRC) contains premotor expiratory neurons that play an important role in cough-related expiratory activity of chest wall and abdominal muscles. Microinjection of D,L-homocysteic acid (DLH) was used to test the hypothesis that local activation of cVRC neurons can suppress the cough reflex. DLH (20 -50 mM, 10 -30 nl) was injected into the region of cVRC in nine anesthetized spontaneously breathing cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Unilateral microinjection of DLH (1-1.5 nmol) elicited bilateral increases in tonic and phasic respiratory ABD EMG activity, and it altered the respiratory pattern and laryngeal motor activities. However, DLH also decreased cough frequency by 51 Ϯ 7% compared with control (P Ͻ 0.001) and the amplitude of the contralateral (Ϫ35 Ϯ 3%; P Ͻ 0.001) and ipsilateral (Ϫ34 Ϯ 5%; P Ͻ 0.001) ABD EMGs during postinjection coughs compared with control. The cough alterations were much less pronounced after microinjection of a lower dose of DLH (0.34 -0.8 nmol). No cough depression was observed after microinjections of vehicle. These results suggest that an endogenous cough suppressant neuronal network in the region of the cVRC may exist, and this network may be involved in the control of cough reflex excitability. excitatory amino acid; brain stem; ventral respiratory group; abdominal; laryngeal CONSIDERABLE PROGRESS HAS been made in the understanding of central cough mechanisms since the first evidence that respiratory neurons in the ventrolateral medulla participated in coughing (14, 21). Our current conceptualization of the neurogenesis of cough holds that there is a common respiratory and cough-generating neuronal network in the brain stem (38,40,41). However, this concept of cough generation cannot explain alterations of cough excitability induced by the administration of antitussive drugs (6, 7) or the elimination of the cough reflex by kainic acid lesions in several brain stem areas that are not involved in respiratory rhythm generation (22,23,35,36). Our laboratory has proposed the existence of a functional element in the cough generation system that we have termed a gate (7). This excitatory element enables a reconfigured respiratory pattern generator to produce single or repetitive coughs and provides excitatory input to expiratory premotoneurons in the medulla (8). Whether the gating mechanism is the sole brain stem control element that regulates coughing or is itself modulated by ...

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

“…9,10,27,43,45,47,53,54). As already mentioned, these responsive structures may comprise, in particular, the caudal ventral respiratory group, in agreement with our previous suggestions (11,43) and those by Bolser and colleagues (9,48). Present results do not allow us to support or to refute the notion of the existence of a coughgating mechanism or any particular pool of neurons specifically relevant to this function.…”

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

“…We also proposed (42) that several neural substrates involved in the regulation of cough (12,16,17,31,44,46,48,56,57) may be sites of action of antitussive drugs. In agreement with our previous suggestion and preliminary results (17,42,44) as well as the proposal by Bolser and colleagues (12,49), the responsive sites may comprise, in particular, the caudal part of the ventral respiratory column (2), i.e., the so-called caudal ventral respiratory group (cVRG), where bulbospinal expiratory neurons are concentrated (6,30,63).…”

“…Interestingly, Poliacek et al (49) showed that unilateral microinjections of DLH into the cVRG of anesthetized cats reduced cough number and associated abdominal thrusts, thus revealing the presence of a cough-suppressant neuronal network within this region. Furthermore, in agreement with previous suggestions (12,17,42,44,49), codeine within the cVRG region proved to have an antitussive effect without a direct action on bulbospinal expiratory neurons (51).The present research was undertaken on pentobarbital-anesthetized, spontaneously breathing rabbits with the main purpose of ascertaining whether the cVRG could be a site of action of different centrally acting antitussive agents and a component of the neural system involved in cough regulation. We used the same antitussive agents already tested within the cNTS (42).…”

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

“…In all instances, no appreciable changes in the pattern of breathing and cough responses were observed. In particular, it is worth noting that galanin and galnon did not cause any significant effect on the cough reflex when microinjected into the caudal ventral respiratory group, a widely recognized site of action of centrally acting antitussive drugs and a neural structure with a prominent role in the regulation of the cough reflex (see e.g., 9,13,14,41,42,48,50).…”

“…Studies undertaken to provide insights into the neural mechanisms subserving the cough reflex may also provide useful suggestions for novel antitussive therapeutic strategies. The cough reflex involves several brain stem structures that also underlie respiratory rhythm generation (e.g., 7,9,10,19,24,27,[47][48][49]55). …”