Effect of long-term treatment with octreotide on rectal sensitivity in patients with non-constipated irritable bowel syndrome.
ABSTRACT Acute administration of octreotide reduces visceral perception and therefore has been suggested as potential treatment for irritable bowel syndrome. Whether prolonged treatment with octreotide also reduces visceral sensitivity and improves gastrointestinal symptoms remains, however, unknown.
To investigate the effect of a slow release preparation of octreotide on rectal sensitivity and symptoms in irritable bowel syndrome patients.
Forty-six non-constipated irritable bowel syndrome patients (52% female, 19-63 years) participated. Before and after 8 weeks of treatment with octreotide (Sandostatin LAR 20 mg i.m.) or placebo, patients underwent a barostat study to assess the rectal sensitivity. During a 2-week run-in period and treatment, abdominal pain, defecation frequency, consistency and symptom relief were scored weekly.
Octreotide, but not placebo, significantly increased the threshold for first sensation. Thresholds for urge to defecate and discomfort/pain and rectal compliance were not altered by either treatment. Octreotide improved stool consistency compared with placebo (loose stools after eight weeks: octreotide: 52%, placebo: 81%, P < 0.05). In contrast, abdominal pain and defecation frequency were not affected.
Although the threshold of first rectal sensation increased and stool consistency improved, long-term treatment with octreotide, at least at the current dose used, has no visceral analgesic effect and fails to improve irritable bowel syndrome symptoms.
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ABSTRACT: Irritable bowel syndrome (IBS) patients exhibit enhanced sensitivity to rectal distention. The somatostatin analog reduces perception of rectal distention in healthy volunteers without modifying rectal resistance. We evaluated whether octreotide has similar effects on rectal perception and resistance in diarrhea-prone IBS patients. Octreotide (100 micrograms s.c.) and placebo were injected in double-blind fashion in eight IBS patients. Rectal balloons measured volumes that evoked increasing levels of perception and intrarectal pressures. After placebo, threshold perception, pressure, urgency and maximal tolerated volume were reported at 18 +/- 5, 46 +/- 8, 72 +/- 7 and 102 +/- 10 ml by the IBS patients, values less than we have observed in healthy volunteers. With octreotide, these sensations were perceived at higher volumes (40 +/- 10, 89 +/- 16, 167 +/- 20 and 202 +/- 25 ml, P < .05) that approximated responses in healthy volunteers. IBS patients exhibited higher rectal pressures at each volume and showed a trend to higher rectal resistance (0.13 +/- 0.02 mmHg/ml) than we have observed in healthy volunteers. These abnormalities were normalized by octreotide. Octreotide did not block the rectoanal inhibitory reflex confirming a lack of effect on local rectal reflex arcs. As with healthy volunteers, IBS patients with diarrhea experience reduced perception of rectal distention after octreotide. Octreotide also reduces elevated rectal pressures in IBS patients, in contrast to healthy volunteers. Thus, octreotide shows potential therapeutic benefit in IBS via dual effects on visceral afferent pathways and rectal wall stiffness.Journal of Pharmacology and Experimental Therapeutics 03/1994; 268(3):1206-11. · 3.89 Impact Factor
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ABSTRACT: Only a fraction of patients with irritable bowel syndrome (IBS) show hypersensitivity to rectal distention. The current study sought to determine if repetitive high-pressure stimulation of sigmoid mechanoreceptors modulates perception of rectal pain and discomfort. In 14 patients with IBS and 11 healthy controls, perception thresholds for discomfort and pain during rectal sensory tracking and verbal descriptor ratings of the perceived intensity of a rectal tonic stimulus were obtained before and after repetitive high-pressure mechanical sigmoid stimulation. Gastrointestinal and psychological symptoms were assessed by questionnaires. Despite heterogeneity in baseline rectal sensitivity in patients with IBS, after sigmoid stimulation, 100% of patients, regardless of baseline sensitivity, developed rectal hyperalgesia manifested by at least two of the following three criteria: lowered thresholds for pain and discomfort and increased viscerosomatic referral and lower abdominal discomfort outlasting the experimental stimulation. This pattern of responses was not observed in any of the healthy controls. In patients with IBS, repetitive stimulation of sigmoid splanchnic afferents results in the development of central sensitization manifested as hyperalgesia and increased viscerosomatic referral during rectal distention and as spontaneous rectosigmoid hyperalgesia in the absence of applied stimuli. Repetitive sigmoid contractions may induce rectosigmoid hyperalgesia in patients with IBS.Gastroenterology 01/1997; 112(1):55-63. · 12.82 Impact Factor
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ABSTRACT: Impaired accommodation and hypersensitivity to distension of the proximal stomach are considered to be important factors in the pathogenesis of dyspeptic complaints. As fundus relaxing agents may be effective in the treatment of these symptoms, insight into the mediators involved in fundic accommodation and associated perceptual responses is important. Therefore, we studied the effect of nitric oxide (NO) synthase inhibition by N(G)-monomethyl-L-arginine (L-NMMA) on fundic tone, postprandial sensations, and gastric perception in healthy volunteers. Eighteen healthy volunteers participated in a double blind, placebo controlled, randomised study. They underwent a gastric barostat study to evaluate the effect of L-NMMA on meal and distension induced sensations and on fundic relaxation in response to oral meal intake, intraduodenal lipid, and glucagon administration. Compared with placebo, L-NMMA decreased fundic volume after oral meal intake (438 (55) v 304 (67) ml; n=8; p<0.05) and during intraduodenal lipid infusion (384 (37) v 257 (43) ml; n=10; p<0.05) but not after glucagon injection (570 (62) v 540 (52) ml; n=4; p=0.4). In addition, basal fundic volume was significantly reduced by L-NMMA. Scores for nausea and satiation were decreased by L-NMMA after oral meal intake but not during intraduodenal lipid infusion. Perception scores to gastric distension were not altered by L-NMMA. NO is involved in maintaining basal fundic tone and in meal induced fundic relaxation in humans, but not in visceral perception.Gut 09/2002; 51(2):212-8. · 10.73 Impact Factor