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Additional file 6: TableS1. Immunohistochemistry conditions.

International audience; Aim: Sacral nerve stimulation (SNS) reduces incontinence episodes and improves the quality of life of patients treated for faecal incontinence. However, the exact mechanism of action of this technique remains unclear. The present article reviews the pertinent neuroanatomy and neurophysiology related to SNS and provides explanations for potential mechanisms of action.Method: A systematic review of the literature was performed for studies of the potential mechanisms of action of SNS, using MEDLINE, PubMed, Embase and the Cochrane Library. Articles dealing with the technique, adverse events and economic evaluations of SNS, as well as literature reviews, were excluded, except for reviews dealing with the mechanisms of action of SNS. The following inclusion criteria were used to select articles: (i) articles in English, (ii) randomized, double-blinded, sham-controlled studies, and (iii) cohort studies. Case–control studies or retrospective studies were cited only when randomized or cohort studies could not be found.Results: We propose three hypotheses to explain the mechanism of action of SNS: (i) a somato-visceral reflex, (ii) a modulation of the perception of afferent information, and (iii) an increase in external anal sphincter activity.Conclusion: The mechanism of action of SNS in patients with faecal incontinence almost certainly depends on the modulation of spinal and ⁄ or supraspinal afferent inputs. Further research on humans and animals will be required to gain a better understanding of the mechanisms of action of SNS.

In a previous study, we established that leptin acts on chemosensitive intestinal vagal mechanoreceptors and that its excitatory effects are blocked by the endogenous interleukin-1beta receptor antagonist (Il-1ra). To determine how interleukin-1beta (Il-1beta) is involved in the action of leptin, we studied the effects of this drug on the single vagal afferent activities of intestinal mechanoreceptors in anaesthetized cats. For this purpose, the activity of 34 intestinal vagal mechanoreceptors was recorded via glass microelectrodes implanted in the nodose ganglion. Il-1beta (1 microg) administered into the artery irrigating the upper part of the intestine activated both the 16 leptin-activated units (type 1 units; P0.01) and the 12 leptin-inhibited units (type 2 units; P0.001), but had no effect on the six leptin-insensitive units. Cholecystokinin (CCK, 10 microg) induced an activatory response only in the two types of Il-1beta-sensitive units. When Il-1beta was administered after CCK, its excitatory effects on type 1 units were enhanced, whereas the excitatory effects on type 2 units were abolished. Pre-treatment with Il-1ra (250 microg) blocked all the effects of Il-1beta and the excitatory effects of leptin on type 1 units, whereas it enhanced the inhibitory effects of leptin on type 2 units. It can therefore be concluded that (i) leptin acts on intestinal vagal mechanoreceptors via Il-1beta in the case of the type 1 units and independently of Il-1beta in the case of the type 2 units, and (ii) type 1 and type 2 units belong to two different populations of vagal afferents that transmit different information about ingestion or inflammation to the CNS, depending on the chemical environment.

International audience; Background: Alverine citrate is commonly used in the treatment of painful affections of the colon.Aim: To determine whether alverine citrate acts on the vagal sensory endings.Methods: Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied.Results: The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5±10 lg/kg), substance P (5± 10 lg/kg) or phenylbiguanide (5±10 lg/kg), a 5-HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present.Conclusions: Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti-spasmodic effects.

International audience; Aim: The study aimed to assess, for the first time, the effectiveness of interferential therapy (IFT) in the treat-ment of slow transit constipation in adults and its impact on the quality of life.Method: All consecutive patients with slow transit constipation diagnosed by symptomology and a colonic transit time (CTT) of > 100 h measured with radiopaque markers were included in this prospective study. IFT was performed for 1 h/day over 3 months. Clinical improvement was based on the stool diary and the Knowles–Eccersley–Scott Symptom and Cleveland Clinic Constipation Scores. Quality of life was assessed with the Gastrointestinal Quality of Life Index questionnaire.Results: Eleven patients with a median age of 51 years were included. At the end of the follow-up period, seven (63.6%) had significantly improved after IFT with a median of 0.66 stools per week [interquartile range (IQR) 0.33–0.66] before treatment and 1.66 (IQR1.33–1.66) after (P = 0.007). The Knowles–Eccersley– Scott Symptom score changed from 30 (IQR 27–33) before treatment to 19 (IQR 17–26) after treatment (P = 0.005) and the Cleveland Clinic Constipation Score from 26 (IQR 25–28) to 17 (IQR 13–24; P = 0.005). The CTT improved from 103 h (IQR 101–113) to 98 h (IQR 94–107; P = 0.02). The Gastrointestinal Quality of Life Index score improved from 60 (IQR 57–63) to 95 (IQR 68–100; P = 0.005).Conclusion: IFT is a new non-invasive treatment for slow transit constipation. Further studies to confirm these results with longer follow-up are necessary.