Key result
Capsaicin inhalation in healthy participants activated medullary regions, with activation in cardiorespiratory areas positively correlated with the subjective urge to cough (r2 = 0.47, 0.48).
Why the study?
Although cortical networks activated by airway irritation had been reported, a directed survey of human brain stem areas activated by airway irritation was needed.
Does capsaicin inhalation activate specific brain stem regions associated with airway irritation in healthy humans?
Cross-Sectional (n=15)
Does capsaicin inhalation activate specific brain stem regions associated with airway irritation in healthy humans?
Effect estimate: r2 = 0.47, 0.48
Capsaicin inhalation activates specific brain stem regions in humans, providing foundational knowledge on the processing of airway irritation that may inform novel cough therapies.
Hypothesis-generating for medullary cough circuits in humans; leaves open therapeutic targeting in chronic cough without practice change.
Coughing is an airway protective behavior elicited by airway irritation. Animal studies show that airway sensory information is relayed via vagal sensory fibers to termination sites within dorsal caudal brain stem and thereafter relayed to more rostral sites. Using functional magnetic resonance imaging (fMRI) in humans, we previously reported that inhalation of the tussigenic stimulus capsaicin evokes a perception of airway irritation (“urge to cough”) accompanied by activations in a widely distributed brain network including the primary sensorimotor, insular, prefrontal, and posterior parietal cortices. Here we refine our imaging approach to provide a directed survey of brain stem areas activated by airway irritation. In 15 healthy participants, inhalation of capsaicin at a maximal dose that elicits a strong urge to cough without behavioral coughing was associated with activation of medullary regions overlapping with the nucleus of the solitary tract, paratrigeminal nucleus, spinal trigeminal nucleus and tract, cardiorespiratory regulatory areas homologous to the ventrolateral medulla in animals, and the midline raphe. Interestingly, the magnitude of activation within two cardiorespiratory regulatory areas was positively correlated ( r2 = 0.47, 0.48) with participants’ subjective ratings of their urge to cough. Capsaicin-related activations were also observed within the pons and midbrain. The current results add to knowledge of the representation and processing of information regarding airway irritation in the human brain, which is pertinent to the pursuit of novel cough therapies. NEW & NOTEWORTHY Functional brain imaging in humans was optimized for the brain stem. We provide the first detailed description of brain stem sites activated in response to airway irritation. The results are consistent with findings in animal studies and extend our foundational knowledge of brain processing of airway irritation in humans.
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Bautista et al. (2019) conducted a cross-sectional in Healthy (n=15). Capsaicin inhalation was evaluated on Correlation between magnitude of activation within cardiorespiratory regulatory areas and subjective ratings of urge to cough (r2 = 0.47, 0.48). Capsaicin inhalation in healthy participants activated medullary regions, with activation in cardiorespiratory areas positively correlated with the subjective urge to cough (r2 = 0.47, 0.48).
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