Yanling Zhang

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain.

Metro driver is the prime person who is responsible for metro operation safety. The mental health of a metro driver is very important for the operation of the subway and requires the driver to keep high mental alertness to monitor the surrounding environment and also handle emergencies under uncertain or dangerous conditions. After a long-term occupational strain, a metro driver is likely to suffer from some mental health problems, such as anxiety and depression, that ultimately threaten the lives of passengers. Therefore, in this study, we focus on the psychological symptoms of metro drivers from the angle of occupational strain and neuroticism. A total of 396 metro drivers from Kunming Rail Transit Operation Co., Ltd. in China were investigated through a questionnaire survey. Symptom Checklist-90, Personal Strain Questionnaire, and NEO-Five-Factor Inventory-Neuroticism Subscale were applied to evaluate the psychological symptoms, occupational strain, and neuroticism in metro drivers, respectively. The surveyed data were analyzed by SPSS software. Based on the data, a path structural equation model was established to explore the correlation among occupational strain, psychological symptoms, and neuroticism. The results show that the scores for psychological symptoms and occupational strain are higher than the Chinese adult norm among metro drivers. The occupational strain, neuroticism, and psychological symptoms are all positively correlated in the metro drivers. Occupational stress has a direct influence on the psychological symptom, while neuroticism plays a partial mediation role between occupational strain and psychological symptoms. The results of this study can be applied to optimize the employee selection system and training system for metro operation companies.

Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2, and mutations that disrupt complex function and/or formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases.