Role of the dorsomedial medulla in suppression of cough by codeine in cats

• Published in: Respiratory physiology & neurobiology Vol. 246; pp. 59 - 66
• Main Authors: Poliacek, Ivan, Simera, Michal, Veternik, Marcel, Kotmanova, Zuzana, Bolser, Donald C., Machac, Peter, Jakus, Jan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2017
• Subjects: Abdominal Muscles - drug effects; Abdominal Muscles - physiopathology; Airway defense; Animals; Antitussive Agents - therapeutic use; Blood Pressure - drug effects; Brainstem; Cats; Codeine - therapeutic use; Cough - drug therapy; Diaphragm - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Female; Lateral tegmental field; Male; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Microinjections; Respiratory motor output; Respiratory Muscles - drug effects; Respiratory Muscles - physiopathology; Solitary tract nucleus; Solitary tract nucleus; Lateral tegmental field; Respiratory motor output; Airway defense; Brainstem
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2017.07.011

•Findings on cough control neuronal network in the NTS and FTL.•Location specific antitussive activity of codeine in the rostral NTS and FTL.•Confirmed limited codeine modulation on temporal features of the cough motor pattern.
The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the lateral tegmental field (FTL) was studied. Experiments were performed on 27 anesthetized spontaneously breathing cats. Electromyograms (EMG) were recorded from the sternal diaphragm and expiratory muscles (transversus abdominis and/or obliquus externus; ABD). Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Bilateral microinjections of codeine (3.3 or 33mM, 54±16nl per injection) in the cNTS had no effect on cough, while those in the rNTS and in the FTL reduced coughing. Bilateral microinjections into the rNTS (3.3mM codeine, 34±1 nl per injection) reduced the number of cough responses by 24% (P<0.05), amplitudes of diaphragm EMG by 19% (P<0.01), of ABD EMG by 49% (P<0.001) and of expiratory esophageal pressure by 56% (P<0.001). Bilateral microinjections into the FTL (33mM codeine, 33±3 nl per injection) induced reductions in cough expiratory as well as inspiratory EMG amplitudes (ABD by 60% and diaphragm by 34%; P<0.01) and esophageal pressure amplitudes (expiratory by 55% and inspiratory by 26%; P<0.001 and 0.01, respectively). Microinjections of vehicle did not significantly alter coughing. Breathing was not affected by microinjections of codeine. These results suggest that: 1) codeine acts within the rNTS and the FTL to reduce cough in the cat, 2) the neuronal circuits in these target areas have unequal sensitivity to codeine and/or they have differential effects on spatiotemporal control of cough, 3) the cNTS has a limited role in the cough suppression induced by codeine in cats.