The analgesic effect of total intravenous anaesthesia with propofol versus inhalational anaesthesia for acute postoperative pain after hepatectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997). METHODS: A prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery. RESULTS: No significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 (p = 0.038, and FDR < 0.1), less nausea (p = 0.011, and FDR < 0.1 on POD 2; p = 0.013, and FDR < 0.1 on POD 3) and constipation (p = 0.013, and FDR < 0.1 on POD 3). CONCLUSION: Propofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy.

Propofol attenuates postoperative hyperalgesia via regulating spinal GluN2B-p38MAPK/EPAC1 pathway in an animal model of postoperative pain.

BACKGROUND: Total intravenous anesthesia with propofol has been shown to reduce postoperative pain in some clinical studies, but knowledge of its underlying analgesic mechanism remains limited. In this study, we compared the analgesic effects of propofol versus isoflurane in an animal model of postoperative pain and evaluated its underlying molecular mechanisms. METHODS: Plantar incision was made in the hind paws of rats under general anesthesia with 2.5% of inhalational isoflurane (isoflurane group) or intravenous infusion of propofol (1.5 mg kg-1  min-1 , propofol group). Mechanical allodynia was assessed by paw withdrawal threshold before and after incision. Spinal dorsal horns (L3-L5) were harvested 1 hr after incision to assess the level of phosphorylated GluN2B, p38MAPK, ERK, JNK, and EPAC using Western blot and immunofluorescence. RESULTS: Mechanical allodynia induced by plantar incision peaked at 1 hr and lasted for 3 days after incision. It was significantly less in the propofol group compared with the isoflurane group in the first 2 hr following incision. The incision-induced increases in phosphorylated GluN2B, p38MAPK, and EPAC1 were significantly reduced in the propofol group. The number of spinal dorsal neurons co-expressed with EPAC1 and c-Fos after the incision was significantly lower in the propofol group. CONCLUSION: Propofol reduced pain responses in an animal model of postoperative pain and suppressed the spinal GluN2B-p38MAPK/EPAC1 signaling pathway. Since the p38MAPK/EPAC pathway plays a critical role in the development of postoperative hyperalgesia, our results provide evidence-based behavioral, molecular, and cellular mechanisms for the analgesic effects of propofol when used for general anesthesia. SIGNIFICANCE: These findings may provide a new mechanism for the postsurgical analgesic effect of propofol, which is particularly interesting during the subacute period after surgery as it is the critical period for the development of persistent postsurgical pain.

Efficacy of Pregabalin in Acute Postoperative Pain Under Different Surgical Categories: A Meta-Analysis.

The efficacy of pregabalin in acute postsurgical pain has been demonstrated in numerous studies; however, the analgesic efficacy and adverse effects of using pregabalin in various surgical procedures remain uncertain. We aim to assess the postsurgical analgesic efficacy and adverse events after pregabalin administration under different surgical categories using a systematic review and meta-analysis of randomized controlled trials.A search of the literature was performed between August 2014 to April 2015, using PubMed, Ovid via EMBASE, Google Scholar, and ClinicalTrials.gov with no limitation on publication year or language. Studies considered for inclusion were randomized controlled trials, reporting on relevant outcomes (2-, 24-hour pain scores, or 24 hour morphine-equivalent consumption) with treatment with perioperative pregabalin.Seventy-four studies were included. Pregabalin reduced pain scores at 2 hours in all categories: cardiothoracic (Hedge's g and 95%CI, -0.442 [-0.752 to -0.132], P = 0.005), ENT (Hedge g and 95%CI, -0.684 [-1.051 to -0.316], P < 0.0001), gynecologic (Hedge g, 95%CI, -0.792 [-1.235 to -0.350], P < 0.0001), laparoscopic cholecystectomy (Hedge g, 95%CI, -0.600 [-0.989 to -0.210], P = 0.003), orthopedic (Hedge g, 95%CI, -0.507 [-0.812 to -0.202], P = 0.001), spine (Hedge g, 95%CI, -0.972 [-1.537 to -0.407], P = 0.001), and miscellaneous procedures (Hedge g, 95%CI, -1.976 [-2.654 to -1.297], P < 0.0001). Pregabalin reduced 24-hour morphine consumption in gynecologic (Hedge g, 95%CI, -1.085 [-1.582 to -0.441], P = 0.001), laparoscopic cholecystectomy (Hedge g, 95%CI, -0.886 [-1.652 to -0.120], P = 0.023), orthopedic (Hedge g, 95%CI, -0.720 [-1.118 to -0.323], P < 0.0001), spine (Hedge g, 95%CI, -1.016 [-1.732 to -0.300], P = 0.005), and miscellaneous procedures (Hedge g, 95%CI, -1.329 [-2.286 to -0.372], P = 0.006). Pregabalin resulted in significant sedation in all surgical categories except ENT, laparoscopic cholecystectomy, and gynecologic procedures. Postoperative nausea and vomiting was only significant after pregabalin in miscellaneous procedures.Analgesic effects and incidence of adverse effects of using pregabalin are not equal in different surgical categories.

Programming membrane fusion and subsequent apoptosis into mammalian cells.

By the delivery of specific natural or engineered proteins, mammalian cells can be programmed to perform increasingly sophisticated and useful functions. Here, we introduce a set of proteins that has potential value in cell-based therapies by programming a cell to target tumor cells. First, the delivery of VSV-G (vesicular stomatitis virus glycoprotein) allowed the cell to undergo membrane fusion with adjacent cells to form syncytia (i.e., a multinucleated cell) in conditions of low pH typically occurring at a tumor site. The formation of syncytia caused the clustering of nuclei along with an integration of the microtubule network and ER. Interestingly, the formation of syncytia between cells that are dynamically blebbing, a mode of migration preferred during tumor metastasis, resulted in the loss of these morphology changes. Lastly, the codelivery of VSV-G with L57R (an engineered photoactivated caspase-7) allowed cells to undergo low pH-dependent membrane fusion followed by blue light-dependent apoptosis. In cell-based therapies, the clearance of syncytia between tumor cells might further trigger an immune response against the tumor.