Published online Mar 14, 2015. doi: 10.3748/wjg.v21.i10.2959
Peer-review started: September 5, 2014
First decision: September 27, 2014
Revised: October 10, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: March 14, 2015
AIM: To investigate the activity of vesicular glutamate transporter-3 (VGLUT3) in a visceral hyperalgesia rat model of irritable bowel syndrome, and the role of mast cells (MCs).
METHODS: Transient intestinal infection was induced by oral administration of Trichinella spiralis larvae in rats. On the 100th day post-infection (PI), the rats were divided into an acute cold restraint stress (ACRS) group and a non-stressed group. Age-matched untreated rats served as controls. The abdominal withdrawal reflex was used to measure the visceromotor response to colorectal distension (CRD). The expression levels of VGLUT3 in peripheral and central neurons were analyzed by immunofluorescence and western blotting.
RESULTS: VGLUT3 expression in the L6S1 dorsal root ganglion cells was significantly higher in the PI group than in the control group (0.32 ± 0.009 vs 0.22 ± 0.008, P < 0.01), and there was no significant difference in the expression of VGLUT3 between MC-deficient rats and their normal wild-type littermates. Immunofluorescence showed that the expression levels of VGLUT3 in PI + ACRS rats were enhanced in the prefrontal cortex of the brain compared with the control group.
CONCLUSION: VGLUT3 is involved in the pathogenesis of visceral hyperalgesia. Coexpression of c-fos, 5-hydroxytryptamine and VGLUT3 after CRD was observed in associated neuronal pathways. Increased VGLUT3 induced by transient intestinal infection was found in peripheral nerves, and was independent of MCs. Moreover, the expression of VGLUT3 was enhanced in the prefrontal cortex in rats with induced infection and stress.
Core tip: It has been shown that visceral hyperalgesia in response to various stimuli from the gut of irritable bowel syndrome (IBS) patients is an important factor in abdominal pain. Our research indicated that the vesicular glutamate transporter 3 (VGLUT3), which concentrates the excitatory neurotransmitter glutamate into synaptic vesicles in peripheral and central neurons, is involved in the pathogenesis of visceral hyperalgesia. An infection-induced increase in VGLUT3 may be one of the main reasons for visceral hyperalgesia in IBS patients.