Background: Visceral hypersensitivity has been evidenced in patients with irritable bowel syndrome (IBS) but its mechanisms remain poorly elucidated. We investigated the spinal transmission of nociceptive signals in IBS patients by analysing the effects of rectal distensions on electromyographic recordings of the somatic nociceptive flexion (RIII) reflex, an objective index of spinal nociceptive processes. Methods: Fourteen IBS and 10 healthy volunteers were included in the study. Slow ramp (40 ml/min) and rapid phasic (900 ml/min, 10, 20, 30, and 40 mm Hg) rectal distensions were randomly performed while the RIII reflex evoked by electrical stimulation of the sural nerve at the ankle was continuously recorded from the ipsilateral biceps femoris. Results: In healthy volunteers, significant progressive inhibition of the RIII reflex was observed during slow ramp distension (61 (13)% of control values) while biphasic effects (facilitation and inhibition) were observed during rapid distensions. In contrast, in IBS patients, the RIII reflex was significantly facilitated during slow ramp distension (139 (15)% of control values) and inhibitions induced by rapid distensions were significantly reduced. Volumes of distension and rectal compliance were similar in both groups. Conclusions: Our results provide direct evidence that a hyperexcitability of spinal nociceptive processes is present in a large subgroup of IBS patients.
Chronic constipation is a common symptom that regularly affects the quality of life of adult patients. Its treatment is mainly based on dietary rules, laxative drugs, perineal rehabilitation and surgical treatment. The French National Society of Coloproctology offers clinical practice recommendations on the basis of the data in the current literature, including those on recently developed treatments. Most are noninvasive, and the main concepts include the following: stimulant laxatives are now considered safe drugs and can be more easily prescribed as a second-line treatment; biofeedback therapy remains the gold standard for the treatment of anorectal dyssynergia that is resistant to medical treatment; transanal irrigation is the second-line treatment of choice in patients with neurological diseases, but it may also be proposed for patients without neurological diseases; and although interferential therapy may be a new promising treatment, it needs further evaluation.
Hypersensitivity during rectal distension has been demonstrated in irritable bowel syndrome (IBS). Studies performed in animals and indirect data in humans suggest that cholecystokinin (CCK) could modulate visceral sensations. The aim of this study was to assess the effects of i.v. infused sulphated cholecystokinin octapeptide (CCK-OP) on rectal sensitivity in response to distension. In eight healthy subjects, rectal sensitivity and compliance were determined during a randomized double-blind study, with four sessions each separated by 7 days. Sensory thresholds and rectal compliance were assessed during slow-ramp (40 mL min-1) and rapid-phasic distensions (40 mL s-1, 5 mmHg stepwise, 1-min duration), and were compared before and during continuous infusion of either saline or CCK-OP at 5, or 20 or 40 ng kg-1 h-1. During rapid phasic distension but not during slow ramp distension, CCK-OP at 40 ng kg-1 h-1 produced a significant decrease in sensory thresholds compared with the basal period. Rectal compliance was not modified by any infusion. At pharmacological doses, CCK-OP decreases sensory thresholds during rapid phasic distension that may preferentially stimulate serosal mechanoreceptors, but has no effect on mucosal mechanoreceptors stimulated during slow ramp distensions. Modulation of rectal sensitivity by CCK could be implicated in the pathogenesis of the rectal hypersensitivity observed in IBS.
Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by partial ferrochelatase deficiency, resulting in protoporphyrin overproduction which is responsible for painful skin photosensitivity. Chronic liver disease is the most severe complication of EPP, requiring liver transplantation in some patients. Data from a mouse model suggest that cytotoxic bile formation with high concentrations of bile salts and protoporphyrin may cause biliary fibrosis by damaging bile duct epithelium. In humans, cholestasis is a result of intracellular and canalicular precipitation of protoporphyrin. To limit liver damage two strategies may be considered: the first is to reduce protoporphyrin production and the second is to enhance protoporphyrin excretion. Bile salts are known to increase protoporphyrin excretion via the bile, while heme arginate is used to decrease the production of porphyrins in acute attacks of hepatic porphyrias. The Griseofulvin-induced protoporphyria mouse model has been used to study several aspects of human protoporphyria including the effects of bile salts. However, the best EPP animal model is an ethylnitrosourea-induced point mutation with fully recessive transmission, named ferrochelatase deficiency (Fech(m1Pas)). Here we investigate the effect of early ursodesoxycholic acid (UDCA) administration and heme-arginate injections on the ferrochelatase deficient EPP mouse model. In this model UDCA administration and heme-arginate injections do not improve the protoporphyric condition of Fech(m1Pas)/Fech(m1Pas) mice.
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