Microinjection of codeine into the region of the caudal ventral respiratory column suppresses cough in anesthetized cats

Abstract

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20-32 nl) in the cVRC reduced cough number by 29% (P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% (P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% (P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30-40 nl) on ABD activity induced by a microinjection of D,L-homocysteic acid (30 mM, 27-40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC D,L-homocysteic acid microinjection (30 mM, 28-32 nl) by 47% (P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid.

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

“…The results also support the hypothesis (42) that several neural substrates involved in cough regulation (12,16,17,31,44,46,48,56,57) may be sites of action of antitussive drugs. They are consistent with previous suggestions (12,17,42,44,49,51) and extend previous findings on the action of antitussive drugs on the cVRG (42,51).…”

“…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).…”

“…J Appl Physiol 109: 1002-1010, 2010. First published July 22, 2010 doi:10.1152/japplphysiol.00406.2010.-We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern.…”

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

“…Noticeably, increases in the cough-related T E were also observed after N-methyl-D-aspartate (NMDA) receptor blockades within the caudal NTS (41,43). On the basis of the differential effects of antitussive drugs on the cough and breathing pattern, Bolser and colleagues (7,50) have proposed the presence of a cough-gating mechanism controlling inspiratory and expiratory burst amplitude as well as cough number, but not phase duration. Present and previous results from our laboratory (e.g., 13, 14, 39 -43) are, at least in part, consistent with this view.…”

“…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).…”