The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects

Abstract

Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin-induced cough in 80 healthy volunteers (mean age 25 yrs).Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33×10 -4 M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces.The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit.These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances.

Antitussive Drugs—Past, Present, and Future

“…In cough evoked by capsaicin, codeine (30 and 60 mg p.o.) had no effect on the sensation of urge to cough or on cough number , and there is no additional effect apparent when capsaicin cough is voluntarily suppressed (Hutchings and Eccles, 1994). As in animal studies, inhaled codeine (50 mg) also failed to inhibit capsaicin-induced cough in normal volunteers (Fuller et al, 1988).…”

Abnormal White Matter Integrity in Chronic Users of Codeine-Containing Cough Syrups: A Tract-Based Spatial Statistics Study

“…Changes in the axial and radial diffusivities (axial, principal longitudinal direction, 1 , and radial, transverse diffusion component, [ Ќ ϭ (2 ϩ 3) / 2]) of clusters showing significant FA decrease were calculated. VOI masks were first extracted on the basis of clusters showing significant intergroup FA differences.…”

“…It has been frequently used as an antitussive agent. 1 It has relatively specific central inhibition of the cough center in the medulla and does not cause respiratory depression. Although codeine is a less addictive opiate than heroin, continued use can result in physical and psychological dependence.…”

Neurophysiology of the cough reflex

“…In experimental animals, breathing can be depressed by general anaesthetics with little decrease in the power of cough reflex, and antitussive drugs can suppress cough with little depression of breathing [10,11]. In humans, induced and natural cough can be suppressed voluntarily, although it is not known at what site in the central nervous system the suppression takes place [12][13][14].…”