We have shown previously in normal subjects that a sensory measure, the Urge-to-
Cough rating, increases at concentrations of inhaled
capsaicin that are lower than those necessary to elicit reflex
cough. This finding suggests that the Urge-to-
Cough may represent an index of the
cough response. Research on
cough in the human has most often employed challenge with inhaled
capsaicin to induce reflex
cough. Current measures of
cough sensitivity in the human provide no information regarding the intensity of
cough. The influence of
codeine on
cough perceptual sensitivity and the relationship to
cough intensity with
capsaicin-induced
cough in normal subjects has not been evaluated. This study determined the effect of
codeine on
capsaicin-induced
cough perceptual sensitivity and motor response in normal subjects in a double-blind, placebo-controlled, crossover study. This approach investigated the relevance of
cough sensitivity, intensity, and sensory modalities in the assessment of
cough suppression in humans. This study consisted of three experimental trials: administration of placebo, 30 mg
codeine and 60 mg
codeine. The study was double-blinded. The order of the three trials was randomized. Respiratory motor pattern was recorded with EMGs from the rectus abdominis, lateral abdominal muscles and eighth intercostal space. The subjects leaned into a fume hood to inspire deeply for 2 s once through a mouthpiece connected to the
nebulizer. A modified Borg scale was used to estimate their Urge-to-
Cough. The experimental trial consisted of eight test solutions of 0-200 microM
capsaicin. Each
solution was presented three times in a randomized block order for a total of 24 presentations. The lowest
capsaicin concentration to elicit a
cough was determined. The lowest
capsaicin concentration to elicit an Urge-to-
Cough greater than zero was identified. The Urge-to-
Cough sensitivity was determined from the log-log slope. For placebo, the Urge-to-
Cough was zero with inhalation of the vehicle and no
coughs were observed. The threshold
capsaicin concentration for subjects to report an Urge-to-
Cough was 15.6 microM (+/-2.6 SEM). The
capsaicin concentration threshold for eliciting a
cough was significantly greater, 39.3 microM (+/-5.6 SEM). As the
capsaicin concentration increased, the magnitude estimation of the Urge to-
Cough increased. The slope of the log-log relationship for the Urge-to-
Cough was 0.94 (+/-0.07 SEM). As the
capsaicin concentration increased, the number and intensity of the
coughs increased. The administration of 30 and 60 mg
codeine had no significant effect on the threshold
capsaicin concentration for the Urge-to-
Cough. There was also no significant
codeine effect on the slope of the log-log Urge-to-
Cough relationship. Thirty and sixty milligram
codeine had no significant effect on the relationship between the
capsaicin concentration and the number and intensity of the
coughs. The results of this study demonstrate that the threshold for a subject to perceive an Urge-to-
Cough was less than the
capsaicin concentration that elicits the
cough motor response. There was a direct relationship between the sensory intensity (magnitude estimation of the Urge-to-
Cough) and the
cough number and intensity. Thus, as the sense of an Urge-to-
Cough increased the
cough motor response increased. Neither the 30 nor 60 mg
codeine affected the perceptual or motor sensitivity to
capsaicin-induced
cough. These results showed that the initial threshold for responding to
capsaicin-induced
cough is the perception of an Urge-to-
Cough, followed by a motor
cough response if the
capsaicin is increased above the perceptual threshold. As the
capsaicin concentration increases, both the perceptual need to
cough and the
cough motor response increase. The response of subjects to inhalation of
capsaicin consisted of both a sensory component leading to perception of an Urge-to-
Cough and motor
cough behavior.