naloxone and Colonic-Diseases--Functional

Opioids change gut motility and secretion, causing delayed intestinal transit and constipation. Endorphins play a role in the constipation troubling some patients with irritable bowel syndrome; hence naloxone, an opioid antagonist, may have a therapeutic role.. To assess the efficacy and safety of an oral formulation of naloxone in irritable bowel syndrome patients with constipation.. A randomized, double-blind, placebo-controlled trial was performed. Patients fulfilling the Rome II criteria for irritable bowel syndrome (constipation-predominant and alternating types) were randomized to receive 8 weeks of treatment with naloxone capsules, 10 mg twice daily, or identical placebo.. Twenty-eight patients entered the study, which was completed by 25. 'Adequate symptomatic relief' was recorded in six of 14 on naloxone and three of 11 on placebo. Whilst the differences were not significant, improvements in severity gradings and mean symptom scores for pain, bloating, straining and urgency to defecate were greater with naloxone than placebo for all parameters. In addition, quality of life assessments improved to a greater extent in patients taking naloxone.. Preliminary results suggest that naloxone is well tolerated and beneficial in patients with irritable bowel syndrome and constipation. A larger clinical trial is needed to provide sufficient statistical power to assess efficacy.

Topics: Administration, Oral; Adult; Colonic Diseases, Functional; Constipation; Delayed-Action Preparations; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Quality of Life; Treatment Outcome

The effects of oxytocin on colonic perception of intraluminal distension were evaluated in 26 patients with irritable bowel syndrome (IBS), using a flaccid bag placed in the descending colon and connected to a computerised barostat.. Symptomatic responses (first sensation and pain) were evaluated during isobaric distensions (4 mm Hg increments, five minute duration, five minute interval with return to zero pressure between each step), performed automatically by the barostat, during a continuous infusion of placebo or various doses of oxytocin (10, 20, 30, and 50 mU/min).. The distension pressure (mean (SD)) required to induce a first abdominal sensation was 17.3 (5.5) mm Hg on placebo, 19.9 (5.8) on oxytocin 10 mU/min (NS), 22.3 (6.0) mm Hg on oxytocin 20 mU/min (p < 0.01), 23.1 (6.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 24.0 (7.1) mm Hg on oxytocin 50 mU/min (p < 0.01). The distension pressure required to induce pain was 24.8 (6.3) mm Hg on placebo, 26.0 (5.8) on oxytocin 10 mU/min (NS), 33.3 (7.8) mm Hg on oxytocin 20 mU/min (p < 0.01), 34.2 (7.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 34.3 (7.9) mm Hg on oxytocin 50 mU/ min (p < 0.01). Compliance curves were not different after placebo and oxytocin injection at the different doses. Naloxone did not inhibit the effect of oxytocin. Oxytocin also did not alter somatic perception, characterised by the RIII reflex at the level of the biceps femori.. Oxytocin significantly increases thresholds for visceral perception in IBS patients at doses equal or to greater than 20 mU/min, possibly by acting at the level of visceral afferents.

Topics: Adult; Colon; Colonic Diseases, Functional; Dose-Response Relationship, Drug; Electric Stimulation; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxytocin; Pain Threshold; Perception; Pressure; Reflex

Topics: Adolescent; Adult; Clinical Trials as Topic; Colonic Diseases, Functional; Female; Humans; Male; Middle Aged; Naloxone; Random Allocation

Topics: Adult; Aged; Amides; Antidiarrheals; Chlorobenzenes; Chronic Disease; Clinical Trials as Topic; Colitis, Ulcerative; Colonic Diseases, Functional; Crohn Disease; Diarrhea; Drug Evaluation; Female; Gastrointestinal Agents; Humans; Isonipecotic Acids; Male; Middle Aged; Naloxone; Nitriles; Piperidines; Placebos; Reflex, Pupillary

To study the effects of mu and kappa opioid receptor agonists and antagonists on the isolated colon strips of rats with cathartic colon.. Cathartic colon model was established by feeding rats with contact laxatives, and effects of mu and kappa opioid receptor agonists and antagonists on electricity-stimulated contraction of isolated colon strips of rats with cathartic colon were observed.. Compared with control group, exogenous mu and kappa agonists inhibited significantly electricity-stimulated contraction of strips of cathartic colon (8.50+/-0.89 mm, 6.24+/-0.91 mm, 3.35+/-0.6 mm vs 11.40+/-0.21 mm P<0.01; 8.98+/-0.69 mm, 6.89+/-0.71 mm, 4.43+/-0.99 mm vs 11.40+/-0.21 mm, P<0.01). In contrast, the exogenous mu antagonist significantly enhanced electricity-stimulated contraction of isolated colon strips (13.18+/-0.93 mm, 15.87+/-0.98 mm, 19.46+/-1.79 mm vs 11.40+/-0.21 mm, P<0.01), but kappa antagonist had no effect on the isolated colon strips of rats with cathartic colon.. Mu and kappa opioid receptors are involved in the regulation of colon motility of rats with cathartic colon.

Topics: Analgesics, Opioid; Animals; Cathartics; Colon; Colonic Diseases, Functional; Constipation; Electric Stimulation; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Female; Gastrointestinal Motility; In Vitro Techniques; Male; Muscle Contraction; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, kappa; Receptors, Opioid, mu

This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome.

Topics: Animals; Animals, Newborn; Behavior, Animal; Colonic Diseases, Functional; Defecation; Disease Models, Animal; Eating; Female; Gastrointestinal Motility; Hyperalgesia; Male; Maternal Deprivation; Naloxone; Narcotic Antagonists; Nociceptors; Pain Threshold; Pregnancy; Rats; Rats, Long-Evans; Stress, Psychological; Weight Gain

1. Noxious colo-rectal distension was applied in conscious rats by acute balloon inflation and the effects observed as abdominal muscle contraction with the threshold typically between 10-40 mmHg. The effects of 5-HT3 receptor antagonists on responses to noxious colo-rectal distension were then studied in both normal rats and those pretreated with 5-hydroxytryptophan (5-HTP). 2. Granisetron and ondansetron (10 micrograms kg-1 and 1 mg kg-1, s.c.) had no effect on visceromotor thresholds to colo-rectal distension in normal rats. 3. Hypersensitivity of the colo-rectum was achieved by systemic administration of a low dose of 5-HTP (10 mg kg-1, s.c.) which lowered the distension pressure required to induce the visceromotor reflex; analysis of variance showed a highly significant treatment effect (F1,11 = 84.26, P < 0.001). 4. Granisetron, zatosetron, bemesetron and renzapride equi-potently increased the threshold values at which distension evoked a visceromotor reflex after dosing with 5-HTP, with a maximal response 3.6 to 4.2 fold above saline controls, at 10 micrograms kg-1, s.c. Metoclopramide (10 micrograms kg-1) also raised the level of distension required to elicit a response. By comparison, tropisetron caused a small, non-significant increase in visceromotor threshold values and only at high doses (1 mg kg-1), whilst ondansetron and BRL 46470 had no significant effects at doses up to 10 mg kg-1. 5. The response to granisetron (10 micrograms kg-1, s.c.) in 5-HTP-treated rats was unaltered by pre-administration of naloxone (5 mg kg-1, s.c.). 6. These results suggest that a 5-HT3-like receptor modulates 5-HTP- evoked visceral hypersensitivity.However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5-HT3 receptor.

Topics: 5-Hydroxytryptophan; Animals; Colon; Colonic Diseases, Functional; Hypersensitivity; Male; Muscle, Smooth; Naloxone; Physical Stimulation; Pressure; Rats; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists

Topics: Adult; Antidepressive Agents; Benzodiazepines; Colonic Diseases, Functional; Dextromethorphan; Diagnosis, Differential; Humans; Loperamide; Naloxone; Parasympatholytics