EFFECTS OF THE SOMATOSTATIN ANALOG OCTREOTIDE ON RECTAL AFFERENT NERVES IN HUMANS

Somatostatin (Som) administered intrathecally to humans has been shown to exert potent analgesic effects on somatic pain, and anecdotal evidence suggests that Som may also relieve visceral pain. In the current study, we used rectal balloon distension in seven healthy volunteers to evaluate the effect of the Som analogue octreotide (Oct; 1.25 mug/kg sc) on four pathways mediated by different visceral afferents that originate in the rectum: conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter, and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum tonically (volume ramp at 20-40 and 400 ml/min) or phasically (intermittent pressure steps of 60 s duration). Pressure thresholds for nonnoxious and noxious sensations in response to slow tonic distension were increased in the presence of rectal lidocaine (20 ml of 2% solution), whereas those to phasic distension were unaffected. Oct significantly increased pressure and volume thresholds for nonnoxious and noxious sensations in response to slow tonic distension but did not further increase thresholds in the presence of intrarectal lidocaine. In contrast, no effect of Oct on rectal sensations was observed during rapid tonic or phasic distension. Oct had no effect on any of the monitored reflex responses. The effect of Oct on rectal sensation in the concentration used in this study was not associated with changes in the rectal wall pressure-volume relationship during any distension protocol. These findings indicate that the inhibitory effect of Oct on rectal sensation is likely to represent a direct effect on a subset of extrinsic primary afferent neurons, with receptive fields in the mucosa.