BACKGROUND Octreotide, a somatostatin analogue, has antinociceptive activity in several models. We studied whether octreotide modifies perception of rectal distention in healthy volunteers and examined its mechanism of action. METHODS Octreotide (100 micrograms, subcutaneously) and placebo were injected in double-blind fashion. Rectal balloons measured volumes that evoked increasing levels of perception. Octreotide's effects on rectal sensation were compared with actions on rectal resistance, rectal motor activity, afferent and efferent anal activity, and somatic perception. RESULTS After octreotide administration, threshold perception, pressure, urgency, and maximal tolerated volume were reported at 62 +/- 4, 185 +/- 11, 269 +/- 17, and 362 +/- 25 mL, which were greater than after administration of placebo (25 +/- 4, 95 +/- 9, 153 +/- 10, and 211 +/- 13 mL, P < 0.01). Rectal pressures, which increased from 9.2 +/- 1.2 mm Hg at 30 mL to 20.2 +/- 1.7 mm Hg at 180 mL after administration of placebo, were not modified by octreotide; this shows a lack of effect on rectal resistance. However, in addition to enhancing volumetric tolerance, maximally tolerated pressures were increased to 42.4 +/- 5.1 mm Hg (P < 0.01) by octreotide. Octreotide increased phasic rectal contractions but did not change anal pressures or block the rectoanal inhibitory reflex, confirming that local rectal reflex arcs are unaffected. Perception of thermal or electrical cutaneous stimulation was unaffected by octreotide showing selectivity for visceral afferent pathways. CONCLUSIONS Octreotide reduces sensation of rectal distention via inhibition of visceral afferent pathways. In contrast, afferent pathways involved in local reflexes and cutaneous perception are not inhibited by octreotide.