Obstructive Lung Diseases |

Antagonism of Substance P and Perception of Dyspnea and Pain in Patients With COPD FREE TO VIEW

Aamir Gilani, MD; Donald Mahler, MD; Alex Gifford, MD; Laurie Waterman, MS; Brian Kupchak, PhD; William Kraemer, PhD
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Dartmouth Hitchcock Medical Center, Lebanon, NH

Chest. 2013;144(4_MeetingAbstracts):740A. doi:10.1378/chest.1692026
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SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 27, 2013 at 04:15 PM - 05:15 PM

PURPOSE: Substance P, an excitatory neuropeptide, is present along with its receptor neurokinin (NK)-1 in the peripheral and central nervous systems and augments respiratory rhythm in animal preparations. The primary objective of this study was to investigate whether substance P 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 chronic obstructive pulmonary disease (COPD) inspired through resistances during practice sessions to identify an individualized target load that provoked breathlessness > 50 mm on a 100 mm visual analog scale. At intervention visits, aprepitant (125 mg) or placebo was administered orally, and patients rated the intensity and unpleasantness of breathlessness during resistive load breathing (RLB) and of pain during immersion of the hand into cold water. Blood levels of substance P and beta-endorphin were measured.

RESULTS: There were no differences in ratings of breathlessness during RLB and of pain during cold water immersion between aprepitant and placebo. After aprepitant, but not with placebo, there were significant increases in substance P (+54 ± 39 %) and beta-endorphin (+27 ± 17 %); these changes were significantly correlated (Spearman r = 0.62; p = 0.01).

CONCLUSIONS: Our results do not support a role for the substance P-NK-1 pathway in the perception of dyspnea or pain in patients with COPD. These findings may be explained by opposing effects of excitatory (substance P) and inhibitory (beta-endorphin) neuropeptides, released after administration of aprepitant, that affect perception of noxious stimuli.

CLINICAL IMPLICATIONS: Of the 50 or more neuropeptides identified in humans, at present time only endogenous opioids have been shown to modulate the perception of dyspnea. An enhanced understanding of the neurobiology of dyspnea is important for developing more effective treatments for this distressful and disabling symptom.

DISCLOSURE: The following authors have nothing to disclose: Aamir Gilani, Donald Mahler, Alex Gifford, Laurie Waterman, Brian Kupchak, William Kraemer

Excitatory and inhibitory neuropeptides orchestrate and modulate different parameters of respiratory activity by targeting specific receptors. In vitro testing using animal preparations have identified the effect of different neuropeptides on respiratory rhythm. We tried to investigate the modulation of dyspnea in human subjects.




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