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Neuropathic pain is a complicated clinical syndrome caused by heterogeneous etiology. Despite the fact that the underlying mechanisms remain elusive, it is well accepted that neuroinflammation plays a critical role in the development of neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be involved in the processing of diverse biological events including cellular development, immunity, and tumor invasion etc. Recent studies have shown that Fascin-1 participates in antigen presentation and the regulation of pro-inflammatory agents. However, whether Fascin-1 is involved in neuropathic pain has not been reported. In the present study we examined the potential role of Fascin-1 by using a rodent model of chronic constriction injury (CCI). Our results showed that Fascin-1 increased rapidly in dorsal root ganglions (DRG) and spinal cord (SC) after CCI. The increased Fascin-1 widely expressed in DRG, however, it localized predominantly in microglia, seldom in neuron, and hardly in astrocyte in the SC. Intrathecal injection of Fascin-1 siRNA not only suppressed the activation of microglia and the release of pro-inflammatory mediators, but also attenuated the mechanical allodynia and thermal hyperalgesia induced by CCI. [ABSTRACT FROM AUTHOR]

This study was designed to detect the modulation manner of melatonin on microglial activation and explore herein possible involvement of mammalian target of rapamycin (mTOR) pathway following traumatic brain injury (TBI). ICR mice were divided into four groups: sham group, TBI group, TBI + sal group and TBI + Melatonin group. A weight-drop model was employed to cause TBI. Neurological severity score (NSS) tests were performed to measure behavioral outcomes. Nissl staining was conducted to observe the neuronal degeneration and wet-to-dry weight ratio indicated brain water content. Immunofluorescence was designed to investigate microglial activation. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate proinflammatory cytokine levels (interleukin-beta (IL-1β), tumor necrosis factor-alpha (TNF-α)). Western blotting was engaged to analyze the protein content of mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase (p70S6K) and S6 ribosomal protein (S6RP). Melatonin administration was associated with markedly restrained microglial activation, decreased release of proinflammatory cytokines and increased the number of surviving neurons at the site of peri-contusion. Meanwhile, melatonin administration resulted in dephosphorylated mTOR pathway. In conclusion, this study presents a new insight into the mechanisms responsible for the anti-neuroinflammation of melatonin, with possible involvement of mTOR pathway. [ABSTRACT FROM AUTHOR]