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Codeine Asymmetrically Inhibits The Laryngeal Adductor Reflex
Author(s) -
Musselwhite M. Nicholas,
Shen Tabitha Y.,
Rose Melanie J.,
Olsen Wendy L.,
Pitts Teresa G.,
Bolser Donald C.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06655
Subject(s) - superior laryngeal nerve , anesthesia , reflex , medicine , stimulation , recurrent laryngeal nerve , adductor muscles , electromyography , anatomy , psychiatry , thyroid
The laryngeal adductor reflex (LAR) is a fundamental airway protective behavior that prevents penetration of material from the upper airway into the trachea. Aspiration risk increases in humans after a single dose of an opioid and pneumonia is a common occurrence in opioid users. The LAR consists of a short latency (~10 ms), short duration (~10 ms) burst (R1) and a longer latency (~40ms) burst (R2) in laryngeal electromyogram (EMG) activity. The R1 LAR is thought to be primarily a brainstem reflex. We hypothesized that systemic administration of codeine, one of the most commonly prescribed opioids, would suppress the R1 LAR in an animal model that robustly expresses airway protective behaviors. The LAR was elicited in anesthetized, spontaneously breathing cats (n=13) by electrical stimulation (2 Hz, 0.1 ms pulse duration) of the superior laryngeal nerve (SLN) or mechanical stimulation of the vocal folds with a von Frey filament. Bilateral thyroarytenoid (TA) and midline posterior cricoarytenoid (PCA) muscle electromyograms (EMGs) were recorded. The R1 LAR manifested as a short latency (approx. 10 ms) evoked response consisting of peaks and troughs in both the TA and the PCA EMGs. Codeine (0.1–10 mg/kg, iv) dose dependently inhibited the magnitude of the contralateral TA and PCA LAR by approximately 60% but had no significant effect on the LAR in the ispilateral TA EMG. Similar lateralization of the effect of codeine was observed in animals in which the LAR was elicited by mechanical stimulation of the vocal folds. These effects were similar in animals whether only one or both SLNs were sectioned. In separate animals, the codeine dose response was conducted after pretreatment with the NMDA antagonist, MK‐801 (10 μg/kg) via the vertebral artery. MK‐801 enabled depression of the TA LAR on the ipsilateral side by iv codeine, but did not enhance the reduction in the contralateral TA or PCA LAR relative to animals that only received this opioid. These findings support lateralized suppression of the LAR by opioids that is mediated by central NMDA receptors. The differing effects of codeine on the LAR in the PCA and ipsilateral TA EMGs suggest that opioids may disrupt laryngeal protective actions through asymmetric positioning of the vocal folds. Support or Funding Information Supported by NIH HL131716 and 3OT2OD023854