Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans

To determine the site of action of opiates in humans, we have studied the effect of systemic and inhaled opiates on cough and increase in respiratory resistance (Rrs) caused by inhaled capsaicin. In 13 subjects, a range of doses of capsaicin inhaled in single breaths given in random order produced a reproducible dose-cough response. Inhalation of a dose of capsaicin that caused fewer than two coughs increased Rrs by 28% (21-35, mean 95% confidence interval). Inhaled codeine (50 mg) and morphine (10 mg) did not alter the cough response. In contrast, both drugs increased base-line Rrs by 24% (16-44) and 13% (3-23), respectively, and significantly reduced the increase in Rrs after inhaled capsaicin (P less than 0.05). Oral codeine (60 mg) significantly (P less than 0.05) reduced the number of coughs at 1 and 2 h but did not alter base-line Rrs or its increase after capsaicin. Intravenous morphine (0.15 mg/kg) significantly reduced the sensitivity of the cough response (P less than 0.05), which was reversed by naloxone. However, there was no significant drug effect on either the base-line Rrs or its increase after capsaicin. Systemic dosing of opiates is therefore required to reduce the cough reflex, whereas inhaled opiates may reduce the increase in Rrs after inhaled capsaicin.