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Neurokinin‐1 receptor antagonism in a human model of visceral hypersensitivity
Author(s) -
WILLERT R. P.,
HOBSON A. R.,
DELANEY C.,
HICKS K. J.,
DEWIT O. E.,
AZIZ Q.
Publication year - 2007
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2006.03190.x
Subject(s) - medicine , hyperalgesia , placebo , tachykinin receptor 1 , allodynia , anesthesia , crossover study , substance p , visceral pain , threshold of pain , gastroenterology , stimulation , pharmacology , receptor , nociception , pathology , neuropeptide , alternative medicine
Summary 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.