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Voltage-gated sodium channel plays a critical role in pain sensation and has been considered as a potential target for the development of analgesic drug. Hainantoxin-III(HNTX-III) is a selective inhibitor of neuronal tetrodotoxin-sensitive voltage-gated sodium channels with similar selectivity for Nav1.7, 1.2 and 1.3 but not for Nav1.4 and Nav1.5 from the venom of the spider O. hainana. The aim of the present study is to investigate the analgesic effect of HNTX-III on inflammatory and neuropathic pain models. In the complete Freund's adjuvant (CFA) model and formalin model of inflammatory pain, HNTX-III produced reversal of hyperalgesia comparable with morphine, and in the spared nerve injury model of pain, HNTX-III inhibited allodynia compared with mexiletine. HNTX-III was also evaluated in a motor coordination assay to assess its propensity for central nervous system side effects, indicating it did not induce impairment of motor coordination. Our findings revealed that HNTX-III significantly alleviated chronic neuropathic pain and acute inflammatory pain and provided a potential template for analgesic drug design in future. [ABSTRACT FROM AUTHOR]

Research in the metal oxide nanoparticles and nanotechnology field is growing. Zinc oxide (ZnO) nanoparticles (NPs) have been widely used in the various products and industries. Regarding the probable toxicity of ZnO NPs on central nervous system (neurotoxicity), the current study was designed to investigate the effects of maternal exposure to ZnO NPs during pregnancy on depressive-like behaviors in mice offspring, using two validated animal models of depression. Thirty pregnant female mice were distributed into three groups (n = 10 for each group). The two experimental groups were injected subcutaneously at gestation day 5, 8, 11, 14, and 17 with 100 µl of ZnO NPs solution at doses of 0.5 and 1 mg/ml, respectively. The control group was treated with a similar subcutaneous injection of saline containing 0.05% Tween-80 as vehicle. Neurobehavioral tests including forced swimming test (FST) and tail suspension test (TST) were used to evaluate depressive-like behaviors in 3-week-old and 6-week-old male and female offspring (n = 10/group). The results of this study indicated that subcutaneous injection of ZnO NPs at 0.5 and 1 mg/ml dose dependently increased the immobility time in 3-week-old and 6-week-old mice in both the FST and TST (P < 0.05). Moreover, increasing age also significantly increased the duration of immobility in both the FST and TST (P < 0.05). In addition, sex differences were observed in behavioral responses, such as female mice were more immobile than male mice in both the FST and TST (P < 0.05). In conclusion, these findings demonstrated that the depressive-like effects of ZnO NPs may be due to its neurotoxic influences during neuronal development. [ABSTRACT FROM AUTHOR]

The cerebellum has long been recognized as the primary center of motor coordination in the central nervous system. Cerebellar neuropeptides have been postulated to be involved in such motor coordination, though this role is not fully understood. We herein investigated the localization of novel neuropeptide, 'manserin' in the adult rat cerebellum. Punctate signals of manserin immunoreactivity were observed in the granular layer of the rat cerebellum. Manserin signals were also observed in the fibers and fiber terminals in the granular layer as well as the molecular layer. Manserin did not localize in Purkinje cells. Interestingly, cerebellar manserin was preferentially colocalized with unipolar brush cells, a class of excitatory granular layer interneuron, which are known to be involved in vestibullocerebellar functions. These results indicate that manserin plays pivotal roles in the cerebellar functions. [ABSTRACT FROM AUTHOR]