Randomised clinical trial: pregabalin attenuates the development of acid-induced oesophageal hypersensitivity in healthy volunteers - a placebo-controlled study.
BACKGROUND
Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown.


OBJECTIVE
To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in healthy humans.


METHODS
Placebo-controlled, double-blind, randomised, cross-over study of 15 healthy volunteers (six women, age 21-56 years). After oesophageal manometry, baseline pain thresholds (PTs) to proximal oesophageal electrical stimulation were determined using bipolar ring electrodes. A 30-min infusion of HCl was performed in the distal oesophagus followed by PT measurements at 30 and 90 min. This protocol was repeated after administration of pregabalin (dosing schedule: 75 mg twice daily for 3 days then 150 mg twice daily for 1 day and then 150 mg on the morning of study) or placebo.


RESULTS
T0 PTs were similar in patients after receiving placebo or pregabalin [mean (s.d.) 32.9 mA (20.5) vs. 34.1 (15.7), P = 0.42]. Pregabalin reduced development of acid-induced hypersensitivity in the proximal oesophagus at 30 min [mean change in PT (C.I.) placebo -6.2 mA (-11.3 to +1.3) vs. pregabalin +0.20 mA (-2.7 to +3.3)] and 90 min [placebo -3.7 mA (-10.0 to +2.0) vs. pregabalin +0.7 mA (-4.7 to 7.3)] overall P = 0.001. Pregabalin reduced median visual analogue scale score for acid-induced pain (1/10 vs. placebo 3/10, P = 0.027).


CONCLUSIONS
Pregabalin attenuates development of secondary hypersensitivity in the proximal oesophagus after distal oesophageal acidification; it may thus have a role in treatment of patients with proven oesophageal pain hypersensitivity.
Wingate Institute, Centre for Digestive Diseases, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
Y C
YC
Chua
K S
KS
Ng
A
A
Sharma
J
J
Jafari
S
S
Surguy
E
E
Yazaki
C H
CH
Knowles
Q
Q
Aziz
D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004935:Esophageal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D006967:Hypersensitivity / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D006851:Hydrochloric Acid