Abstract
Background: The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of dyspnea by administering aprepitant, a selective antagonist that blocks NK-1 receptor signaling.
Methods: Sixteen patients (age, 70 ± 6 years) with COPD completed the study. At intervention visits, aprepitant (125 mg) or placebo was administered orally, and patients rated breathlessness during resistive load breathing (RLB). Blood levels of substance P and beta (β)-endorphin were measured.
Results: After aprepitant, but not with placebo, there were significant increases in substance P (+54 ± 39 %) and β-endorphin (+27 ± 17 %); changes were significantly correlated (Spearman r = 0.62; p = 0.01). There were no differences in ratings of breathlessness during RLB between interventions.
Conclusions: Our results do not support a role for the substance P-NK-1 pathway in the perception of dyspnea in patients with COPD. These findings may be explained by opposing effects of excitatory (substance P) and inhibitory (β-endorphin) neuropeptides, released after administration of aprepitant, that affect perception.
- © 2013 ERS