Probiotic Lactobacillus rhamnosus GG (LGG) and prebiotic prevent neonatal inflammation-induced visceral hypersensitivity in adult rats.

BACKGROUND: Increasing evidence indicates a positive effect of probiotics on the nervous system. The objective of this study was to determine if probiotic Lactobacillus rhamnosus GG (LGG) and/or prebiotics polydextrose/galactooligosaccharide (PDX/GOS) can alter the colonic sensitivity in a neonatal rat model of chronic visceral hyperalgesia and to determine whether altered sensitivity is associated with changes in neurotransmitter levels in the brain. METHODS: Chronic visceral hyperalgesia was induced in rats by intracolonic administration of zymosan for 3 days during postnatal day 14-16 (P14-P16). After weaning (P21), these pups were divided into groups that received either (1) control diet (CD), (2) PDX/GOS, (3) LGG, or (4) PDX/GOS + LGG. These diets were continued until visceral sensitivity was tested at P60. The viscero-motor response (VMR) to graded colorectal distension (CRD) was determined by measuring the electromyographic (EMG) activity from the abdominal external oblique muscles. The levels of neurotransmitters and biogenic amines were quantified in the frontal cortex, subcortex, brain stem, and cerebellum. KEY RESULTS: At P60, the VMR to CRD in the neonatal zymosan-treated rats was significantly higher than neonatal saline-treated rats. In contrast, neonatal zymosan-treated rats that received PDX/GOS or LGG did not exhibit visceral hyperalgesia. The levels of serotonin, noradrenaline, and dopamine were significantly altered in LGG-treated rats compared to other groups. CONCLUSIONS & INFERENCES: Results document that in rats LGG can attenuate neonatally induced chronic visceral pain measured in adulthood. Prolonged intake of LGG alters some key brain neurotransmitters and biogenic amines that could be involved in pain modulation.

AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure.

BACKGROUND: We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices. METHODS: In molecular study, we examined GluA1 and GluA2 expression and phosphorylation in membrane preparations and in the isolated postsynaptic densities (PSDs) from rats receiving acute esophageal exposure of either saline (control group) or 0.1 N HCl (experimental group). In electrophysiological study, the effect of selective AMPA receptor (Ca(2+) permeable) antagonist IEM-1460 and CaMKII inhibitor KN-93 was tested on responses of cortical neurons during acid infusion to address the underlying molecular mechanism of acid-induced sensitization. KEY RESULTS: The acid exposure significantly increased expression of GluA1, pGluA1Ser(831) , and phosphorylated CaMKIIThr(286) , in the cortical membrane preparations. In isolated PSDs, a significant increase in pGluA1Ser(831) was observed in acid-treated rats compared with controls. Microinjection of IEM-1460 or KN-93 near the recording site significantly attenuated acid-induced sensitization of cortical neurons. CONCLUSIONS & INFERENCES: The underlying mechanism of acid-induced cortical sensitization involves upregulation and CaMKII-mediated phosphorylation of GluA1. These molecular changes of AMPA receptors subunit GluA1 in the cortical neurons might play an important role in acid-induced esophageal hypersensitivity.