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Neurokinin-1 receptor antagonism in a human model of visceral hypersensitivity.

Abstract：

BACKGROUND:Substance P acting via the neurokinin-1 receptor is involved in the development of hyperalgesia, although studies using neurokinin-1 receptor antagonists (NK-1RA) in human somatic pain have been disappointing. AIM:To evaluate whether Substance P is involved in the development of human visceral pain/hyperalgesia using a selective NK-1RA. METHODS:Using a validated human model of acid-induced oesophageal allodynia, pain thresholds to electrical stimulation (mA) were measured in the proximal oesophagus and the foot (somatic control), pre- and for 4 h postdistal oesophageal acid in 14 healthy subjects, using a double-blind, randomized, two-period, crossover study. Measurements were taken on the third day of dosing with either an oral NK-1RA or matching placebo, with 2 weeks washout between periods. RESULTS:Baseline pain threshold did not differ between treatments (proximal oesophagus 37 +/- 7.4 mA NK-1RA vs. 38 +/- 10.1 placebo P = 0.81, foot 40 +/- 15 mA NK-1RA vs. 38 +/- 14 placebo P = 0.68). NK-1RA did not attenuate the reduction in pain threshold in the proximal oesophagus postacid infusion (AUC-394 +/- 279 NK-1RA vs. -262 +/- 397 placebo P = 0.54). CONCLUSIONS:The lack of effect of NK-1RA on oesophageal pain threshold in our model does not support a role for Substance P in the development of acid-induced oesophageal allodynia.

journal_name

Aliment Pharmacol Ther

journal_title

Alimentary pharmacology & therapeutics

authors

Willert RP,Hobson AR,Delaney C,Hicks KJ,Dewit OE,Aziz Q

doi

10.1111/j.1365-2036.2006.03190.x

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

309-16

issue

3

eissn

0269-2813

issn

1365-2036

pii

APT3190

journal_volume

25

pub_type

杂志文章,随机对照试验

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