sildenafil-citrate and Irritable-Bowel-Syndrome

Visceral tone supposedly affects gut sensitivity in irritable bowel syndrome (IBS). Sildenafil increases nitric oxide and influences visceral compliance.. To evaluate the effects of sildenafil tone inhibition on rectal sensitivity.. Eight controls and 21 IBS patients (Rome II) were enrolled in a double-blind study, after dosing with placebo or sildenafil (50 mg p.o.). Thresholds for first sensation, first desire to defecate, pain and supraliminar pain were the sensory endpoints, measured with a barostat and 600-mL rectal bag. Pain (100-mm VAS) and depression-anxiety (Hamilton questionnaire) were scored.. Irritable bowel syndrome rectal compliance and sensory-endpoint thresholds were similar to controls. Five IBS patients had pain threshold lower than controls 95% confidence interval (hypersensitive). Depression score was greater in IBS than controls (11.9 ± 1.3 vs. 6.3 ± 2.5, P = 0.036). In IBS, pain intensity was nonsignificantly higher (37.6 ± 5.3 mm vs. 23.4 ± 8.5 mm, P = 0.064) and supraliminar pain intensity was greater (45.6 ± 5.4 mm vs. 25.9 ± 5.1 mm, P = 0.044) than controls. IBS rectal relaxation increased volume (155.4 ± 41.3 mL vs. 118.8 ± 47.7 mL, P = 0.004) and tension (193.1 ± 118.6 mmHg mL(-1) vs. 133.2 ± 98.1 mmHg mL(-1) , P = 0.019) for triggering first desire to defecate but not for other perceptions. Sildenafil increased volume for both first desire to defecate and pain in the hypersensitive IBS patients. Sildenafil increased rectal compliance only in diarrhoea-IBS. Mixed-IBS obtained higher anxiety (12.9 ± 1.3 vs. 5.9 ± 3.1, P < 0.05) and depression scores (13.9 ± 1.9 vs. 6.3 ± 2.5, P < 0.05) and reported more intense supraliminar pain (53.6 ± 9.8 mm vs. 25.9 ± 5.1 mm, P < 0.05) than controls.. Rectal relaxation following dosing with sildenafil 50 mg increased the first desire to defecate threshold in IBS as a whole, but decreased pain only in the hypersensitive subset. Mixed-IBS presented higher supraliminar pain and anxiety-depression scores.

Topics: Adult; Defecation; Double-Blind Method; Female; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Mood Disorders; Muscle Tonus; Nitric Oxide; Pain Measurement; Pain Threshold; Phosphodiesterase 5 Inhibitors; Piperazines; Psychiatric Status Rating Scales; Purines; Rectum; Severity of Illness Index; Sildenafil Citrate; Statistics, Nonparametric; Sulfones

Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro. Sildenafil stimulates the nitric oxide guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS).. In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration of sildenafil (50 mg p.o.). Perception was scored on a graded scale of 0-6. At the end of a distension series an anatomic questionnaire was filled out by the subjects.. Sildenafil significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/- 25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased by sildenafil both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged.. Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated.

Topics: Adult; Case-Control Studies; Cyclic GMP; Female; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Middle Aged; Muscle Tonus; Nitric Oxide; Piperazines; Pressure; Probability; Prospective Studies; Purines; Rectum; Reference Values; Sensitivity and Specificity; Sensory Thresholds; Severity of Illness Index; Sildenafil Citrate; Statistics, Nonparametric; Sulfones