Behavioral and regional brain responses to inhalation of capsaicin modified by painful conditioning in humans.
Cough is a defense mechanism that protects the airways and lungs in response to airway irritation. The sensory neurons involved in detecting airway irritants and the neural pathways mediating cough share similarities with those that encode pain from the body. Painful conditioning stimuli applied to one body site are known to reduce the perception of pain at another. However, whether the neural regulation of cough is influenced by painful stimuli is not known.What are the behavioral and neural outcomes of painful conditioning stimuli on urge-to-cough (UTC) and cough evoked by inhaled capsaicin?Sixteen healthy participants underwent psychophysical testing and functional magnetic resonance imaging while completing a series of capsaicin inhalations to induce an UTC and cough. The responses associated with capsaicin inhalation without pain were compared with those after the application of painful conditioning stimuli.There were significant decreases behaviorally of 18.7±17.3% (p<0.001) and 47.0±30.8% (p<0.001) in participants UTC ratings and cough frequencies respectively during the application of pain. UTC ratings were reduced by 24.2±36.5% (p<0.005) and increased by 67±40% (p<0.001) for capsaicin and saline inhalation respectively during the scanning session. Painful conditioning stimuli were associated with widespread decreases in regional brain responses to capsaicin inhalation (p<0.001). Several brain regions showed levels of reduced activation due to painful conditioning that correlated with related changes in behavioral responses during scanning (R2 = 0.53).Pain-related decreases of cough and UTC are accompanied by widespread changes in brain activity during capsaicin inhalation, suggesting that pain can modify the central processing of inputs arising from the airways. A mechanistic understanding of how cough and pain processing interact within the brain may help develop more effective therapies to reduce unwanted coughing.