SNFGE SNFGE
 
Thématique :
- Intestin/Nutrition/Troubles fonctionnels
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Docteur Pauline JOUET
Coup de coeur :
 
 
Gastroenterology
  2016/01  
 
  2016 Jan 2. pii: S0016-5085(15)01862-4  
  doi: 10.1053/j.gastro.2015.12.034.  
 
  Histamine Receptor H1-mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome.  
 
  Wouters MM, Balemans D, Van Wanrooy S, Dooley J, Cibert-Goton V, Alpizar YA, Valdez-Morales EE, Nasser Y, Van Veldhoven PP, Vanbrabant W, Van der Merwe S, Mols R, Ghesquière B, Cirillo C, Kortekaas I, Carmeliet P, Peetermans WE, Vermeire S, Rutgeerts P, Augustijns P, Hellings PW, Belmans A, Vanner S, Bulmer DC, Talavera K, Vanden Berghe P, Liston A, Boeckxstaens GE  
  http://www.ncbi.nlm.nih.gov/pubmed/?term=Histamine+Receptor+H1-mediated+Sensitization+of+TRPV1+Mediates+Visceral+Hypersensitivity+and+Symptoms+in+Patients+With+Irritable+Bowel+Syndrome.  
 
 

BACKGROUND & AIMS:

Histamine sensitizes the nociceptor TRPV1 and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo controlled trial.

METHODS:

Using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsies collected from 9 patients with IBS (ROME 3 critera) and 15 healthy subjects. Sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsies was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 years; range, 18-65 years; 34 female). After a 2 week run-in period, subjects were randomly assigned to groups given either the HRH1 antagonist ebastine (20 mg/day; n=28) or placebo (n=27) for 12 weeks. Rectal biopsies were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12 week period. Patients were followed for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary endpoint of the study was the effect of ebastine on the symptom score evoked by rectal distension.

RESULTS:

TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared to those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsies from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this effect could be reproduced by histamine and imidazole acetaldehyde. Compared to subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief (ebastine 46% vs placebo 13%; P=.024) and reduced abdominal pain scores (ebastine 39±23 vs placebo 62±22, P=.0004).

CONCLUSION:

In studies of rectal biopsies from patients, we found that HRH1-mediated sensitization of TRPV1 is involved in IBS. Ebastine, an antagonist of HRH1, reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS. Inihbitors of this pathway might be developed as a new treatment approach for IBS. ClinicalTrials.gov no: NCT01144832.

 
Question posée
 
L’hypersensibilité viscérale en cas de syndrome de l’intestin irritable est-elle en rapport avec une sensibilisation des récepteurs nociceptifs TRPV1 par l’histamine ?
 
Question posée
 
L’étude de biopsies rectales chez des patients SII en comparaison à des volontaires sains montre qu’il existe une sensibilisation anormale des récepteurs TRPV1 qui passe par l’activation des récepteurs histaminiques HRH1. De plus chez des patients ayant un SII, l’administration d’ébastine , un antagoniste des récepteurs HRH1, pendant 12 semaines, en comparaison à un placebo, améliore significativement la réponse à une distension rectale (diminution des symptômes) et les symptômes de SII.
 
Commentaires

Une piste de traitement du SII très intéressante devant être confirmée dans des études avec un plus grand nombre de patients …

 
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