Mechanisms of Probiotic VSL#3 in a Rat Model of Visceral Hypersensitivity Involves the Mast Cell-PAR2-TRPV1 Pathway

  • Ying-Jie Li
  • Cong DaiEmail author
  • Min JiangEmail author
Original Article



Mast cells (MCs), PAR2 and TRPV1, play a key role in the regulation of visceral pain. Several studies have found that probiotics regulate visceral sensitivity.


The purpose of the current study was to explore the role of MC-PAR2-TRPV1 in VH and the mechanism of VSL#3 in a rat model of VH.


A total of 64 rats were randomly divided into eight groups: Control VH, VH + ketotifen, VH + FSLLRY-NH2, VH + SB366791, VH + VSL#3, VH + VSL#3 + capsaicin, and VH + VSL#3 + SLIGRL-NH2. The rat model of VH was induced by acetic acid enema and the partial limb restraint method. VH was assessed by the abdominal withdrawal reflex score. MCs in colonic tissue were detected by the toluidine blue staining assay. The expression of PAR2 and TRPV1 in DRGs (L6–S1) was measured by immunohistochemistry and Western blotting.


The established VH was abolished by treatment with ketotifen, a mast cell stabilizer FSLLRY-NH2, a PAR2 antagonist SB366791 a TRPV1 antagonist, and probiotic VSL#3 in rats. The administration of ketotifen or probiotic VSL#3 caused a decrease in mast cell number in the colon and decreased PAR2 and TRPV1 expression in DRGs. Intrathecal injection of FSLLRY-NH2 or SB366791 caused decreased expression of PAR2 and/or TRPV1 in DRGs in VH rats. SLIGRL-NH2, a PAR2 agonist, and capsaicin, a TRPV1 agonist, blocked the effects of probiotic VSL#3.


The probiotic VSL#3 decreases VH in rat model of VH. The mechanism may be related with the mast cell-PAR2-TRPV1 signaling pathway.


Irritable bowel syndrome Probiotics VSL#3 Visceral hypersensitivity Mast cells PAR2 TRPV1 



This research was supported by the National Nature Science Foundation of China (No. 81300273), the Fund for Scientific Research of The First Hospital of China Medical University (No. FSFH2O1702) and the Liaoning Science and Technology Foundation (No. 20170541052).

Compliance with ethical standards

Conflict of interest

The author declares that they have no conflict of interest.

Supplementary material

10620_2018_5416_MOESM1_ESM.tif (8 mb)
HE staining of colonic segments A. Control group B. VH group C. VH + ketotifen group D. VH + FSLLRY-NH2 group E. VH + SB366791 group F. VH + VSL#3 + SLIGRL-NH2 group G. VH + VSL#3 + capsaicin group H. VH + VSL#3 group; n = 8 per group. Scale bar, 200 μm (TIFF 8219 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastroenterology, First Affiliated HospitalChina Medical UniversityShenyang CityChina

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