Brain-derived neurotrophic factor (BDNF) is released from activated microglia during neuropathic pain and is hypothesized to downregulate the expression of the potassium chloride cotransporter 2 (KCC2) via the TrkB receptor. Previous studies reported that KCC2 is downregulated 5 min after the plantar injection of formalin in rats; however, the mechanism behind this decrease in KCC2 expression during acute inflammatory pain remains unknown. In this study, we determined whether the TrkB receptor contributes to the expression of KCC2 during the acute pain. Five minutes after the plantar injection of formalin in rats, the ratio of KCC2-immunoreactive area in layer II of the spinal cord significantly decreased on the stimulated side compared to the unaffected side. On the other hand, this response was inhibited by the injection of a kinase inhibitor, K252a, in the subarachnoid space 15 min before the formalin injection. These findings suggest that in acute pain, the TrkB receptor may contribute to the decrease in the expression of KCC2.Cation chloride cotransporters, such as the sodiumpotassium chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2), play an important role in the movement of chlorine ions in neurons (8,14,17). NKCC1 is mainly expressed in the central nervous system, and KCC2 is mainly expressed in the superficial dorsal horn (12). NKCC1 increases intracellular sodium ions (Na + ), potassium ions (K + ) and chlorine ions (Cl − ), whereas KCC2 decreases intracellular K + and Cl − ions. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is present in the dorsal horn of the spinal cord, but the expression level of these cotransporters sometimes reverses the effect of GABA to have an excitatory effect. Compared with adult neural cells, immature neural cells express more NKCC1 and less KCC2; therefore, the intracellular concentration of Cl − is maintained at a high level, and the changes in the direction and amount of Cl − inflow when the GABA-A receptor opens its ion channel reverses the inhibitory effect of GABA to an excitatory effect (14,17). In addition, the excitatory effect of GABA has been confirmed in several experimental pain conditions, such as neuropathic pain (3). Previous reports have shown that in neuropathic pain, brain-derived neurotrophic factor (BDNF), which is released from activated microglia, switches the effect of GABA on spinal cord layer II neurons to the excitatory mode (2) and that via the TrkB receptor, BDNF reduces KCC2 expression in the dorsal horn of the spinal cord (11). These data suggest that in neuropathic pain, the reduced expression of KCC2 may switch the effect of GABA from the inhibitory mode to the excitatory mode and cause the aggravation of pain and that microglia are a major regulator of the expression levels of KCC2. According to recent studies, chloride cation co-

Hepatic resection can cause postoperative thrombocytopenia that may increase the potential risk of epidural hematoma associated with catheter removal, and the presence of co-existing liver disease heightens concerns for postoperative crucial thrombocytopenia.

Volatile anesthetics are speculated to cause postoperative nausea and vomiting via stimulation of the chemoreceptor trigger zone (CTZ). However, the precise mechanism underlying the emetic action of these drugs is not well understood. In this study, we assessed whether isoflurane induced the expression of c-Fos, a neuronal activation marker, in the area postrema (AP), the locus of the CTZ, in rats, which do not have vomiting action. Male rats were exposed to 1.3% isoflurane for 0 to 240 min, or to various concentrations of isoflurane (0, 1.3%, or 2.6%) for 120 min.Finally, the rats were exposed to 1.3% isoflurane for 120 min after ondansetron administration. After the treatments, immunohistochemistry of the rat AP was performed using c-Fos antibody staining. One-way analysis of variance showed that isoflurane exposure significantly increased c-Fos expression in the AP; however, the rats pretreated with 4 mg/kg ondansetron showed significantly decreased c-Fos expression. Moreover, we evaluated the effect of the anesthetic on inducing pica in the rats, and found that kaolin intake was not influenced by isoflurane exposure.Overall, these results suggest that isoflurane activates AP neurons and may be involved in the emetic mechanism of isoflurane. This study further suggests the feasibility of using rats as a model for studying emetic mechanisms of drugs, despite their lack of vomit action.

For several decades, the neurotoxicities of anesthetics to the developing brain have been reported by many researchers focusing on various phenomena such as apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral abnormalities. According to these reports, signals via N-methyl-D-aspartate receptors (NMDA-r) and/or γ-aminobutyric acid type A receptors (GABA-r) are implicated in the anesthetic neurotoxicity. On the other hand, during brain development, NMDA-r and GABA-r are also recognized to play primary roles in neural cell migration. Therefore, anesthetics exposed in this period may influence the neural cell migration of neonates, and increase the number of hilar ectopic granule cells, which are reported to be a cause of continuous neurological deficits. To examine this hypothesis, we investigated immunohistochemically granule cell distribution in the hippocampal dentate gyrus of Wistar/ST rats after nitrous oxide (NO) exposure. At postnatal day (P) 6, 5-bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells. Then, rats were divided into groups (n = 6 each group), exposed to 50% NO at P7, and evaluated at P21. As a result, we found that ectopic ratios (ratio of hilar/total granule cells generated at P6) were decreased in rats at P21 compared with those at P7, and increased in NO exposed rats for over 120 min compared with the other groups. These results suggest that 50% NO exposure for over 120 min increases the ratios of ectopic granule cells in the rat dentate gyrus.