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

Abstract

Pregabalin, an α2δ ligand, is used clinically to treat somatic pain. A prior study suggested that pregabalin reduces distension-induced pain while increasing rectal compliance. We aimed to quantify effects of pregabalin on colonic sensory and motor functions and assess relationships between sensory effects and colonic compliance. We conducted a randomized, double-blind, placebo-controlled, parallel-group study of a single oral administration of 75 or 200 mg of pregabalin in 62 healthy adults (aged 18-75 yr). Subjects underwent left colon intubation. We assessed "stress-arousal symptoms", compliance, sensation thresholds, sensation ratings averaged over four levels of distension, fasting and postprandial colonic tone, and phasic motility index (MI). Analysis of covariance (adjusted for age, sex, body mass index, and corresponding predrug response) and proportional hazard models were used. There were no clinically important differences among treatment groups for demographics, predrug compliance, tone, MI, and sensation. Treatment was associated with reduced energy and increased drowsiness but no change in tension or relaxation. Sensation ratings averaged over the four distension levels were lower for gas sensation [overall effect P = 0.14, P = 0.05 (pregabalin 200 mg vs. placebo)] and for pain sensation [overall effect P = 0.12, P = 0.04 (pregabalin 200 mg vs. placebo)]. The magnitude of the effect of 200 mg of pregabalin relative to placebo is on average a 25% reduction of both gas and pain sensation ratings. Pregabalin did not significantly affect colonic compliance, sensation thresholds, colonic fasting tone, and MI. Thus 200 mg of pregabalin reduces gas and pain sensation and should be tested in patients with colonic pain.

Trial registration: ClinicalTrials.gov NCT01094808.

Figures

Fig. 1.

Experimental protocol.

Fig. 2.

Study design and participant demographics and baseline features. BOP, balloon operating pressure; BMI, body mass index.

Fig. 3.

Effect of pregabalin on posttreatment mean sensation ratings of gas (A) and pain (B) on visual analog scale (VAS) over 4 distension pressures. Data shown are means ± SD. A: overall effect of treatment on gas sensation, analysis of covariance (ANCOVA), P = 0.14; 200 mg pregabalin vs. placebo, P = 0.05. B: overall effect of treatment on pain sensation, ANCOVA, P = 0.12; 200 mg pregabalin vs. placebo, P = 0.04.

Fig. 4.

A: symptoms used to evaluate effects of treatment on measures of stress. B: comparisons of posttreatment stress-arousal scores (least-square means adjusted for minor differences in groups observed at baseline) show significant effect of treatment on energy and drowsiness levels. *Overall differences among the 3 groups unadjusted for 2 comparisons. Note that 200 mg of pregabalin differed from placebo (P = 0.031, Dunnett's test), but not 75 mg of pregabalin for energy scores, whereas, for the drowsiness scores, both 75 mg and 200 mg of pregabalin were borderline (P = 0.062 for both, Dunnett's test).