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


OBJECTIVE
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.
Willert
R P
RP
GI Sciences Group, Manchester University, CSB, Hope Hospital, Salford, UK.
Hobson
A R
AR
Delaney
C
C
Hicks
K J
KJ
Dewit
O E
OE
Aziz
Q
Q
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000209:etiology*; D010147:Pain Measurement; D017288:Pain Threshold; D014781:Viscera
D064729:Neurokinin-1 Receptor Antagonists