Scalp nerve block with ropivacaine has been shown to provide perioperative analgesia. However, the best concentration of ropivacaine is still unknown for optimal analgesic effects. We performed a prospective study to evaluate the effects of scalp nerve block with varied concentration of ropivacaine on postoperative pain and intraoperative hemodynamic variables in patients undergoing craniotomy under general anesthesia. Eighty-five patients were randomly assigned to receive scalp block with either 0.2% ropivacaine, 0.33% ropivacaine, 0.5% ropivacaine, or normal saline. Intraoperative hemodynamics and post-operative pain scores at 2, 4, 6, 24 hours postoperatively were recorded. We found that scalp blockage with 0.2% and 0.33% ropivacaine provided adequate postoperative pain relief up to 2 h, while administration of 0.5% ropivacaine had a longer duration of action (up to 4 hour after craniotomy). Scalp nerve block with varied concentration of ropivacaine blunted the increase of mean arterial pressure in response to noxious stimuli during incision, drilling, and sawing skull bone. 0.2% and 0.5% ropivacaine decreased heart rate response to incision and drilling. We concluded that scalp block using 0.5% ropivacaine obtain preferable postoperative analgesia compared to lower concentrations. And scalp block with ropivacaine also reduced hemodynamic fluctuations in craniotomy operations. About 10% to 20% patients undergoing craniotomy suffered severe pain and more than 30% experienced moderate pain as per Guilfoyle et al. 1. These experiences with pain may disturb patient sleep patterns and prolong hospital stays 2. Abrupt increases in heart rate (HR) and blood pressure (BP) resulting from dramatic stimuli like incisions, drilling, and screwing cause potential morbidities and mortalities due to elevation of intracranial pressure (ICP) in patients 3,4. Generally, opioids are used for relieving hemodynamic fluctuations and reducing postoperative pain, however, it may delay recovery time, contribute to extreme sedation, and interfere with postoperative neurological examinations. In addition, adverse effects of opioids such as nausea and vomiting, and respiratory depression may result in a rise of ICP or mask the signs of increased ICP. Since there is such an emphasis on controlling the adverse effects of opioid administration, postoperative pain after craniotomy is frequently uncontrolled 1. Easing hemodynamic perturbation and relieving postoperative pain are important concerns of neuroanesthesiologists and are also necessary components of the Enhanced Recovery After Surgery (ERAS). With advances in modern anesthesia come the development of short-acting analgesics, mainly remifentanil, transition analgesics, and conjunction analgesics that can be used instead of opioids to treat postoperative pain 5. Scalp never block (SNB), the blockage of nerves that innervate the involved region of the scalp about surgery 6 , was developed due to its potential benefits for effective regional anesthesia administration 7 , which promotes d...

Primary damage or dysfunction of the nervous system may cause or initiate neuropathic pain. However, it has been difficult to establish an effective treatment for neuropathic pain, as the mechanisms responsible for its pathology remain largely unknown. Autophagy is closely associated with the pathological process of neurodegenerative diseases, neuropathic injury and cancer, among others. The aim of the present study was to examine the changes in the autophagy-lysosomal pathway and discuss the effects of autophagy on allodynia, hyperalgesia and astrocyte activation in neuropathic pain. A neuropathic pain model was induced by chronic constriction injury (CCI) in rats. Inducers and inhibitors of autophagy and lysosomes were used to assess autophagy, allodynia, hyperalgesia and astrocyte activity. Neuropathic pain was found to induce an increase in the levels of the autophagy-related proteins, LC3II and Beclin 1 and, and in those of the lysosomal proteins, lysosomal-associated membrane protein type 2 (LAMP2) and Ras-related protein Rab-7a (RAB7), whereas p62 levels were found to decrease from day 1 to 14 following CCI. The autophagy inducer, rapamycin, further increased the LC3II, Beclin 1, lysosomal-associated membrane protein 2 (LAMP2) and Ras-related protein Rab-7a (RAB7) expression levels, and decreased the p62 expression levels, which were accompanied by alleviation of allodynia, hyperalgesia and astrocyte activation in the rats subjected to CCI; the autophagy inhibitor, 3-methyladenine, reversed these effects. The use of the lysosomal inhibitors, bafilomycin and chloroquine, resulted in the accumulation of LC3II and Beclin 1, a decrease in the levels of LAMP2 and RAB7, and the exacerbation of allodynia, hyperalgesia and astrocyte activation in rats with neuropathic pain. On the whole, the findings of this study indicate that neuropathic pain activates autophagy, which alleviates mechanical and thermal hyperalgesia and suppresses astrocyte activity. Therefore, neuropathic pain induced by CCI in rats appears to be mediated via the autophagy-lysosomal pathway.

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Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.