The urge-to-cough and cough motor response modulation by the central effects of nicotine

Abstract

The urge-to-cough is a respiratory sensation that precedes the cough motor response. Since affective state modulates the perception of respiratory sensations such as dyspnoea, we wanted to test whether nicotine, an anxiolytic, would modulate the urge-to-cough and hence, the cough motor response. We hypothesized that withdrawal from and administration of nicotine in smoking subjects would modulate their anxiety levels, urge-to-cough and cough motor response to capsaicin stimulation. Twenty smoking (SM) adults (8F, 12M; 22+/-3 years; 2.9+/-2.0 pack years) and matched non-smoking (NS) controls (22+/-2 years) were presented with randomized concentrations of capsaicin (0-200 microM) before and after nicotine (SM only) gum and/or placebo (SM and NS) gum. Subjects rated their urge-to-cough using a Borg scale at the end of each capsaicin presentation. Cough number and cough motor pattern were determined from airflow tracings. Subjects completed State-Trait Anxiety Inventory (STAI) questionnaires before and after gum administration. SM subjects that withdrew from cigarette smoking for 12 h exhibited an increase in anxiety scores, a greater number of coughs and higher urge-to-cough ratings compared to NS subjects. Administration of nicotine gum reduced anxiety scores, cough number and urge-to-cough ratings to match the NS subjects. There was no effect of placebo gum on any of the measured parameters in the SM and NS groups. The results from this study suggest that modulation of the central neural state with nicotine withdrawal and administration in young smoking adults is associated with a change in anxiety levels which in turn modulates the perceptual and motor response to irritant cough stimulants.

Fig. 1

Average number of expulsive events in the NS (top) and SM (middle) groups before (closed squares) and after (open circles) placebo gum administration, and following nicotine gum administration in the SM group (bottom). Symbols indicate significant differences: € significantly different from 0, 5, 15, 25, 50, 100 µM capsaicin (pre- and post-trials); * significantly different from 0, 5, 10, 25, 50 µM capsaicin (pre- and post-trials); # significantly different from 0, 5, 10, 25 µM capsaicin (pre- and post-trials); & significantly different from 0, 5, 10 µM capsaicin (pre- and post-trials); § significantly different from 0, 5, 10, 25 µM capsaicin (pre-trial only); ¥ significantly different from the corresponding pre-trial value.

Fig. 2

Comparison of post-trial expulsive events following placebo gum administration in NS (open triangles) and SM (closed squares) groups, and in the SM group following nicotine gum administration (closed circles). * indicates significant differences from the corresponding post-trial nicotine (SM) and post-trial placebo (NS) values. There were no differences between post-trial nicotine (SM) and post-trial placebo (NS) values.

Fig. 3

Cough motor patterns before (solid) and after (hatched) placebo gum administration in NS subjects (top), SM subjects (middle) and after nicotine gum administration in SM subjects (bottom). The total number of cough reaccelerations (CR) and expiratory reflexes (ER) at 100, 150 and 200 µM of capsaicin was summed for each group and condition.

Fig. 4

Average urge-to-cough ratings before (closed squares) and after (open circles) placebo gum administration in the NS (top) and SM (middle) groups, and following nicotine gum administration in the SM group (bottom). Symbols indicate significant differences: € significantly different from 0, 5, 15, 25, 50, 100 µM capsaicin (pre- and post-trials); * significantly different from 0, 5, 10, 25, 50 µM capsaicin (pre- and post-trials); # significantly different from 0, 5, 10, 25 µM capsaicin (pre- and post-trials); & significantly different from 0, 5, 10 µM capsaicin (pre- and post-trials); § significantly different from 0, 5, 10, 25 µM capsaicin (pre-trial only); ¥ significantly different from the corresponding pre-trial value.

Fig. 5

Comparison of post-trial expulsive events following placebo gum administration in the NS (open triangles) and SM (closed squares) groups, and in the SM group following nicotine gum administration (closed circles). * indicates significant differences from the corresponding post-trial nicotine (SM) and post-trial placebo (NS) values. There were no differences between post-trial nicotine (SM) and post-trial placebo (NS) values.

Fig. 6

Relationship between the average number of expulsive events and the average urge-to-cough ratings before (closed squares) and after (open circles) placebo gum administration in the NS (top) and SM (middle) groups, and following nicotine gum administration in the SM group (bottom). For every incremental increase in the urge-to-cough ratings, approximately one expulsive event was produced. There were no differences in this relationship (i.e. slope) between groups (SM vs NS) or treatment (nicotine vs placebo).

Fig. 7

Relationship between the average number of expulsive events and the average urge-to-cough ratings following placebo gum administration in the NS (open triangles) and SM (closed squares) groups, and in the SM group following nicotine gum administration (closed circles). Nicotine withdrawal or administration did not change the sensitivity (i.e. slope) of the cough response to urge-to-cough ratings. However, nicotine withdrawal increased the magnitude of this relationship such that SM subjects rated higher urge-to-cough sensations and produced a greater number of coughs at high capsaicin concentrations compared with NS subjects. Administration of nicotine reduced this effect so that the SM response was the same as that for the NS subjects.

Fig. 8

Capsaicin concentration at the urge-to-cough and the cough thresholds before and after placebo gum administration in the NS (solid bars) and SM (hatched bars) groups, and in the SM group before and after nicotine gum administration (open bars). The urge-to-cough threshold occurred at a lower capsaicin concentration compared with the cough threshold. There were no differences between groups (NS vs SM), treatments (nicotine vs placebo) or trials (pre- vs post-trial). * indicates a significant difference from the corresponding urge-to-cough threshold.