Introduction Oesophageal acid infusion in humans induces primary and secondary hyperalgesia due to peripheral and central sensitisation, respectively.1 Pregabalin is a centrally acting modulator of voltage-sensitive calcium channels which reduces neuropathic pain by attenuating the release of multiple neurotransmitters2 in the CNS. Its efficacy in reducing acid-induced oesophageal hypersensitivity has not been explored.
Methods Single-centre, placebo-controlled, double-blind, randomised, two-period, cross-over study of 15 healthy volunteers (21–52 years, 9 males) attending on three visits. On visit 1, after oesophageal manometry, pain thresholds (PTs) to oesophageal electrical stimulation were determined using bipolar ring electrodes positioned in the proximal and distal oesophagus. Thereafter, a 30 min infusion of HCL was performed in the distal oesophagus. PT was measured again at both sites at 30 and 90 min after the acid infusion. The same methods were repeated for three visits. Participants were then given either pregabalin or placebo after visits 1 and 2. The intervals were at least; 1 week between visits 1 and 2, and 2 weeks between visits 2 and 3 (to allow time for drug washout). The dose of pregabalin used was 75 mg bd for 3 days, 150 mg bd for 1 day and 150 mg od.
Results The median decrease in PT at 30 min after acid, compared to baseline in the proximal oesophagus was significantly less after treatment with pregabalin. This pattern was maintained even at 90 min after acid, but to a lesser degree (Abstract 061). The subjective score of pain to acid infusion was also reduced while on placebo compared to pregabalin (VAS median of 3 vs 1, p=0.0270). The baseline PTs before acid infusion at placebo and pregabalin visits were not significantly different (p=0.42). There were no differences in the change in post-acid PT between pregabalin and placebo in the distal oesophagus.
Conclusion Pregabalin prevents the development of secondary hyperalgesia in the proximal oesophagus after distal oesophageal acidification, both on objective and subjective assessments of pain. It has no significant effect on the site of acid exposure, indicating that it acts to reduce central sensitisation and is not analgesic. Studies of pregabalin in patients with acid-induced oesophageal hypersensitivity are warranted.