• Korean Journal of Psychosomatic Medicine
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• v.20 no.2
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• pp.135-138
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• 2012

The pathophysiology of functional gastrointestinal disorder(FGID) is not completely understood, but the importance of the 'Brain-Gut Axis(BGA)' model in FGID is being increasingly recognized. The BGA model is a bidirectional, hard-wired and homeostatic relationship between the central nervous system(CNS) and the enteric nervous system(ENS) via neural, neurohormonal and neuroimmunological pathways. In addition, the BGA model would provide a rationale for the use of psychotropics on FGID. The authors experienced two cases in which duloxetine, a serotonin-norepinephrine reuptake inhibitor, was effective in relieving FGID symptoms as well as psychiatric symptoms such as depression and hypochondriacal anxiety. Therefore we discuss the vignettes from the perspective of BGA theory. Duloxetine showed efficacy in these two patients by reducing visceral hypersensivity (bottom-up regulation) and by relieving depression and anxiety(top-down regulation).

• The Korean Journal of Pain
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• v.25 no.4
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• pp.228-237
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• 2012

Background: Milnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats. Methods: Sixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20). Results: There were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes. Conclusions: Based on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.

• Molecular & Cellular Toxicology
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• v.4 no.1
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• pp.31-44
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• 2008

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity. Although it has been shown that lateral septum is involved with the FST-related behavior, it is not clear whether antidepressant treatments could alter the FST-induced gene expression profile in the lateral septum. In the present study, the gene expression profiles in response to FST and reboxetine pretreatment were observed in the lateral septum of rats. Reboxetine is known as a most selective serotonin norepinephrine reuptake inhibitor. In addition, we compared the changes in gene expression profile between reboxetine response and nonresponse groups, which were determined by counting FST-related behavior. After FST, lateral septum from controls and reboxetine pretreated group were dissected and gene expression profiles were assessed using an Affymetrix microarray system containing 15,923 genes. Various genes with different functions were changed in reboxetine response group compared with reboxetine nonresponse group, In particular, pleiotrophin, orexin receptor 2, serotonin 2A receptor, neuropeptide Y5 receptor and thyroid hormone receptor $\beta$ were decreased in reboxetine response group, but Lim motif-containing protein kinase 1 (Limk1) and histone deacetylase 1 (HDAC1) were increased. Although further studies are required for direct roles of these genes in reboxetine response, the microarray may provide tools to find out potential target genes and signaling pathways in antidepressant response.