Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

BACKGROUND: Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. RESULTS: In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. CONCLUSION: These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in clinical pain therapy

Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

BACKGROUND: Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. RESULTS: We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. CONCLUSION: These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli

COVID-19 prevention and control measures and experiences during the 14th National Games of China: a qualitative interview study

BackgroundThe 14th National Games was the first sporting mass gathering to be held in China in the context of the COVID-19 pandemic. It may increase the risk of severe acute respiratory syndrome coronavirus 2 transmission. In order to reduce the spread of the virus during the 14th National Games, the Chinese government took a series of public health measures, and ultimately no confirmed cases were found in the 14th National Games venues.ObjectiveThis study aimed to discuss preventive and control measures used to respond to the COVID-19 pandemic during the 14th National Games.MethodsFive experts were selected for this study using a snowball sampling method, and semistructured and in-depth interviews were conducted. Based on grounded theory, the transcriptions were analysed and coded using Nvivo 12 software.ResultsA theoretical model of the COVID-19 prevention and control measures at the 14th National Games of China was constructed. The model contains seven main components: the health risks of mass gatherings, crowd management, emergency medical care, allocation of emergency medical resources, pandemic emergency drills, the pandemic prevention and control management platform (Quanyuntong app), and emergency response plans.ConclusionThe study showed that the deployment of emergency medical resources was the most important for mass gatherings. This study not only expanded the applications of grounded theory but also serves as a reference for future scholars when conducting more in-depth empirical studies on public health countermeasures for mass gatherings and can inform organizers when holding mass gatherings

Knowledge, attitudes, and practices associated with bioterrorism preparedness in healthcare workers: a systematic review

IntroductionBioterrorism is an important issue in the field of biosecurity, and effectively dealing with bioterrorism has become an urgent task worldwide. Healthcare workers are considered bioterrorism first responders, who shoulder essential responsibilities and must be equipped to deal with bioterrorism. This study aims to extract and summarize the main research components of the bioterrorism knowledge, attitude, and practice dimensions among healthcare workers.MethodThis study utilized a systematic review research design based on the PRISMA 2020 guidelines. A literature search was conducted in the PubMed, Web of Science, and Scopus databases for peer-reviewed literature, and the Mixed Methods Appraisal Tool (MMAT) version 2018 was used to assess the quality of the literature.ResultA total of 16 studies were included in the final selection. Through the analysis and summary of the included studies, three main aspects and 14 subaspects of the knowledge dimension, three main aspects and 10 subaspects of the attitude dimension, and two main aspects and six subaspects of the practice dimension were extracted.ConclusionThis study conducted a literature review on bioterrorism knowledge, attitudes, and practices for healthcare workers based on the PRISMA 2020 guidelines. The findings can guide improvements in health literacy and provide beneficial information to professional organizations that need to respond effectively to bioterrorism