μ-Opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbances

Abstract

Mu-opioid receptor agonists depress tidal volume, decrease chest wall compliance, and increase upper airway resistance. In this study, potential neuronal sites and mechanisms responsible for the disturbances were investigated, dose-response relationships were established, and it was determined whether general anesthesia plays a role. Effects of micro-opioid agonists on membrane properties and discharges of respiratory bulbospinal, vagal, and propriobulbar neurons and phrenic nerve activity were measured in pentobarbital-anesthetized and unanesthetized decerebrate cats. In all types of respiratory neurons tested, threshold intravenous doses of the micro-opioid agonist fentanyl slowed discharge frequency and prolonged duration without altering peak discharge intensity. Larger doses postsynaptically depressed discharges of inspiratory bulbospinal and inspiratory propriobulbar neurons that might account for depression of tidal volume. Iontophoresis of the micro-opioid agonist DAMGO also depressed the intensity of inspiratory bulbospinal neuron discharges. Fentanyl given intravenously prolonged discharges leading to tonic firing of bulbospinal expiratory neurons in association with reduced hyperpolarizing synaptic drive potentials, perhaps explaining decreased inspiratory phase chest wall compliance. Lowest effective doses of fentanyl had similar effects on vagal postinspiratory (laryngeal adductor) motoneurons, whereas in vagal laryngeal abductor and pharyngeal constrictor motoneurons, depression of depolarizing synaptic drive potentials led to sparse, very-low-frequency discharges. Such effects on three types of vagal motoneurons might explain tonic vocal fold closure and pharyngeal obstruction of airflow. Measurements of membrane potential and input resistance suggest the effects on bulbospinal Aug-E neurons and vagal motoneurons are mediated presynaptically. Opioid effects on the respiratory neurons were similar in anesthetized and decerebrate preparations.

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

“…Fentanyl, in doses of 20 -40 g/kg, was previously shown to consistently abolish membrane potential hyperpolarization and respiratory rhythmic phrenic nerve discharges, so that caudal expiratory neurons fire tonically during phrenic nerve apnea (16). In all three experiments of the present study, 30 g/kg doses of fentanyl produced tonic discharges (n ϭ 3 cells, one from each experiment; see Fig.…”

“…Another issue investigated was whether or not D 1 R agonists alleviate opioid-evoked tonic discharges of caudal medullary expiratory neurons, an effect that was previously observed in pentobarbital-anesthetized and unanesthetized decerebrate cats (16), in chloralose-anesthetized dogs (18) and in motor nerve fibers that innervate the expiratory muscles of the chest wall in decerebrate rabbits (12). Because caudal medullary expiratory neurons provide excitatory synaptic drive to expiratory motoneurons (19), prevention of tonic discharges by D 1 R agonists would suggest effectiveness against chest wall rigidity caused by opiates…”

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

“…A single preparation was employed to test the effects of each antitussive drug. Drug concentrations were in the same range as those previously used in in vivo preparations (4,13,19,21,22,35,50,56). All drugs were dissolved in 0.9% NaCl solution.…”

Postoperative Apnea Induced by Fentanyl and Other Multiple Respiratory-Modulating Factors

“…Besides, we experienced a difficulty in mechanical ventilation via a face mask at the onset of apnea. It indicated that opioid-induced laryngeal closure might take some role in the respiratory arrest [16]- [19]. The aforementioned mechanisms are only speculative, and we are unable to propose explicit mechanisms that produced apnea in the patient.…”