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

Abstract

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.

Inhibitory modulation of the cough reflex by acetylcholine in the caudal nucleus tractus solitarii of the rabbit

“…Several brainstem areas appear to contribute to the generation and regulation of cough responses in mammals (e.g. Gestreau et al, 1997;Bongianni et al, 1998;Jakus et al, 2008;Mutolo et al, 2002b;Poliacek et al, 2004Poliacek et al, , 2005Poliacek et al, , 2014Shannon et al, 2004;Simera et al, 2013; see also Mutolo, 2017). Recent findings obtained mainly in the rabbit (for review see Mutolo, 2017) have led to the proposal that two medullary structures play a prominent role in the control of cough reflex responses and are sites of action of antitussive or protussive drugs, i.e.…”