Influence of Codeine on Swallow in the Anesthetized Cat: Evidence for Peripheral and Central Actions of Opioids to Induce Dysregulation of Deglutition

Abstract

Systemic administration of opioids has been associated with aspiration and swallow dysfunction in humans. The extent to which these outcomes are due to solely central, or both central and peripheral actions, of these drugs is unknown. Codeine is a commonly prescribed opioid that has both central and peripheral actions to affect the cough reflex in animal models. We speculated that systemic administration of codeine would induce dysfunctional swallowing and that this effect would have a peripheral component. Experiments were conducted in spontaneously breathing, anesthetized cats (n=19). The animals were tracheotomized and EMG electrodes were placed in upper airway and chest wall respiratory muscles for recording swallow related motor activity. The animals were allocated into three groups: vagal intact (VI), cervical vagotomy (CVx), and supra‐nodose ganglion vagotomy (SNVx). A dose‐response to intravenous codeine (0.1–10 mg/kg) was performed in each animal. Swallowing was elicited by injection of 3 ml of water into the oropharynx. Results demonstrated a significant dose‐related increase in spontaneous swallowing (per 7 minute period between doses) in each group (VI: vehicle 0.2±0.2 to 10 mg/kg codeine 6.6±4.0, SNVx: vehicle 0.2±0.2 to 10 mg/kg codeine 4.0±2.3, CVx: vehicle 2.3±1.3 to 13±6.0 10 mg/kg codeine). Additionally, the number of induced swallows after vehicle was significantly higher in the VI group than in SNVx (p<0.04), and in the CVx compared to the SNVx group at 10mg/kg (p<0.05). Codeine also demonstrated dose‐dependent effects on upper airway motor drive during the induced swallow trials. The thyropharyngeus muscle EMG activation was significantly increased in the VI and CVx groups by 2–4 fold in a dose‐related manner (p<0.01). Also, in the CVx group, the geniohyoid muscle EMG activation was significantly increased (p<0.05). Under control conditions the presence of spontaneous swallows is rare, and their presence in response to codeine supports a strong central action and likely a dysregulation of the inhibitory influences on the swallow pattern generator. Unlike cervical vagotomy, section of the vagus nerve rostral to the nodose ganglion eliminates superior laryngeal nerve afferents. At the highest dose of codeine, the reduced spontaneous swallow number in the SNVx group relative to CVx is consistent with a peripheral excitatory action of codeine either on pharyngeal/laryngeal receptors or in the nodose ganglion itself.Support or Funding InformationSupported by OT2OD023854‐01, HL109025, HL131716.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.