Contribution of medullary raphé to control of coughing—Codeine trials in cat

Poliaček, Ivan; Simera, Michal; Veternik, Marcel; Machac, Peter; Baráni, H; Visnovcova, N; Halašová, Erika; Jakus, J

doi:10.1016/j.resp.2012.08.010

Cited by 7 publications

(14 citation statements)

References 54 publications

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“…The magnitude of this change suggests that the physiological significance of the prolongation may be limited. Similar changes in temporal characteristics of cough motor pattern (that included also prolongations of CTE and C-TE2) were seen when codeine was microinjected in the medullary raphé (Poliacek et al, 2012). …”

Section: Discussionmentioning

confidence: 54%

“…Systemic and intra-vertebral delivery as well as local application of codeine in other brainstem regions resulted in no significant modulation of cough inspiratory activity (Bolser et al, 1999; Bolser and Davenport, 2002; Poliacek et al, 2010; Poliacek et al, 2012). However, codeine microinjections into the rNTS and mainly in the FTL reduced cough amplitudes of DIA activity.…”

Section: Discussionmentioning

confidence: 91%

“…We eliminated this cough trial from the analysis due to unstable and reduced coughing. This transient reduction in cough excitability after a delay or gap between tracheobronchial stimulation trials occurred regularly even in vehicle treated animals (Poliacek et al, 2010, 2012, 2017). …”

Section: Methodsmentioning

confidence: 90%

“…Hradec Králové, Czech Republic) were performed in the NTS or FTL. The drug was dissolved in artificial cerebrospinal fluid that was prepared in our laboratory (aCSF; ALZET Osmotic Pumps, California, USA; Poliacek et al, 2012). Single barrel glass micropipettes (tip diameter 15–60 μm) were used for pressure microinjection of solutions.…”

Section: Methodsmentioning

confidence: 99%

“…However, this population of expiratory pre-motoneurons, transmitting expiratory motor drive from the brainstem circuits to the spinal motoneurons (Iscoe, 1998), is relatively insensitive to codeine and unlikely to be responsible for cough suppression (Poliacek et al, 2010). In response to challenge of the medullary raphé with codeine, the excitability and motor output of tracheobronchial cough was depressed by a small amount (Poliacek et al, 2012). Considering that codeine is one of the most widely prescribed drugs to treat cough, there is still a poor understanding of its mechanisms (Haji et al, 2012, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

Poliaček

Simera

Veternik

et al. 2017

Respiratory Physiology & Neurobiology

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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 33 mM, 54 ± 16 nl 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 (3.3 mM 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 (33 mM 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.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Poliaček

Simera

Veternik

et al. 2017

Respiratory Physiology & Neurobiology

Self Cite

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Differential Effects of Kainic Acid Lesions in Medullary Raphe on Cough and Sneeze in Anesthetized Rabbits

Simera

Poliaček

Veternik

et al. 2013

Neurobiology of Respiration

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The effects of microinjections of the excitatory neurotoxin kainic acid (2 mg/ml; 49 ± 1 nl) on the mechanically induced tracheobronchial cough, sneeze, and solitary expulsions from the trachea were examined in 11 anesthetized rabbits. Kainic acid was injected into the medulla (1.6-2.8 mm rostral to the obex, 1.4-1.6 and 2.9-3.2 mm below the dorsal medullary surface). Blood pressure, esophageal pressure (EP), and electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD) were recorded. Kainic acid reduced the number of coughs (means ± SE) from 3.8 ± 2.0 to 0.9 ± 0.7 (p = 0.016), the amplitude of DIA cough from 90 ± 11 to 42 ± 13 % (p = 0.004), ABD EMG moving average from 103 ± 9 to 37 ± 15 % (p = 0.006), and inspiratory from 0.67 ± 0.13 to 0.36 ± 0.12 kPa (p = 0.013) and expiratory EP from 1.70 ± 0.54 to 0.89 ± 0.46 kPa (p = 0.008). Kainic acid had no effect on the number of sneeze reflexes nor did it affect solitary expulsions from the trachea. These effects were accompanied by significant increases in systemic blood pressure and respiratory rate. Spatiotemporal analysis of the cough and sneeze reflexes revealed increases in the duration of cough active expiratory phase, in the intervals between maxima of DIA and ABD EMG discharges, and in the active portion of total cough phase duration. Our findings suggest a diverse role of raphe neurons in the central control of motor airway responses such as coughing and sneezing. A complex function of raphe neurons in the generation of the cough motor pattern also is suggested.

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