Protective effect and mechanism of injection of glutamate into cerebellum fastigial nucleus on chronic visceral hypersensitivity in rats

Abstract Aims We investigated the effects of chemical stimulation of cerebellum fastigial nucleus (FN) on the chronic visceral hypersensitivity (CVH) and its possible mechanism in rats. Main methods We stimulated the FN by microinjecting glutamate into the FN, in order to explore whether the cerebellum fastigial nucleus played a role on CVH in rat. The model of CVH was established by colorectal distension (CRD) in neonatal rats. Abdominal withdrawal reflex (AWR) scores, pain threshold, and amplitude of electromyography (EMG) were used to assess the hyperalgesia. Key findings We showed that microinjection of l -glutamate (Glu) into the FN markedly attenuated hyperalgesia. The protective effect of FN was prevented by pretreatment with the glutamate decarboxylase inhibitor, 3-mercaptopropionic acid (3-MPA) into the FN or GABA A receptor antagonist, bicuculline (Bic) into the LHA (lateral hypothalamic area). The expressions of protein Bax, caspase-3 were decreased, but the expression of protein Bcl-2 was increased after chemical stimulation of FN. These results indicated that the FN participated in regulation of CVH, and was a specific area in the CNS for exerting protective effects on the CVH. In addition, LHA and GABA receptor may be involved in this process. Significance Our findings might provide a new and improved understanding of the FN function, and might show an effective treatment strategy for the chronic visceral hypersensitivity.