Effect of the α2δ ligand, pregabalin, on colonic sensory and motor functions in healthy adults

Pregabalin, an α2δ ligand, is usedclinically to treat somatic pain. A prior study suggested that pregabalinreduces distension-induced pain while increasing rectal compliance.We aimed to quantify effects of pregabalin on colonic sensoryand motor functions and assess relationships between sensory effectsand colonic compliance. We conducted a randomized, double-blind,placebo-controlled, parallel-group study of a single oral administrationof 75 or 200 mg of pregabalin in 62 healthy adults (aged 18-75yr). Subjects underwent left colon intubation. We assessed "stressarousalsymptoms", compliance, sensation thresholds, sensation ratingsaveraged over four levels of distension, fasting and postprandialcolonic tone, and phasic motility index (MI). Analysis of covariance(adjusted for age, sex, body mass index, and corresponding predrugresponse) and proportional hazard models were used. There were noclinically important differences among treatment groups for demographics,predrug compliance, tone, MI, and sensation. Treatment wasassociated with reduced energy and increased drowsiness but nochange in tension or relaxation. Sensation ratings averaged over thefour distension levels were lower for gas sensation [overall effect P 0.14, P 0.05 (pregabalin 200 mg vs. placebo)] and for painsensation [overall effect P 0.12, P 0.04 (pregabalin 200 mg vs.placebo)]. The magnitude of the effect of 200 mg of pregabalinrelative to placebo is on average a 25% reduction of both gas and painsensation ratings. Pregabalin did not significantly affect colonic compliance,sensation thresholds, colonic fasting tone, and MI. Thus 200mg of pregabalin reduces gas and pain sensation and should be testedin patients with colonic pain.