Neurons derived from human-induced pluripotent stem cells express mu and kappa opioid receptors.

Neuroprotection studies have shown that induced pluripotent stem (iPS) cells have the possibility to transform neuroprotection research. In the present study, iPS cells were generated from human renal epithelial cells and were then differentiated into neurons. Cells in the iPS-cell group were maintained in stem cell medium. In contrast, cells in the iPS-neuron group were first maintained in neural induction medium and expansion medium containing ROCK inhibitors, and then cultivated in neuronal differentiation medium and neuronal maturation medium to induce the neural stem cells to differentiate into neurons. The expression of relevant markers was compared at different stages of differentiation. Immunofluorescence staining revealed that cells in the iPS-neuron group expressed the neural stem cell markers SOX1 and nestin on day 11 of induction, and neuronal markers TUBB3 and NeuN on day 21 of induction. Polymerase chain reaction results demonstrated that, compared with the iPS-cell group, TUBB3 gene expression in the iPS-neuron group was increased 15.6-fold. Further research revealed that, compared with the iPS-cell group, the gene expression and immunoreactivity of mu opioid receptor in the iPS-neuron group were significantly increased (38.3-fold and 5.7-fold, respectively), but those of kappa opioid receptor had only a slight change (1.33-fold and 1.57-fold increases, respectively). Together, these data indicate that human iPS cells can be induced into mu opioid receptor- and kappa opioid receptor-expressing neurons, and that they may be useful to simulate human opioid receptor function in vitro and explore the underlying mechanisms of human conditions.

Comparison Between Intraoperative Two-Space Injection Thoracic Paravertebral Block and Wound Infiltration as a Component of Multimodal Analgesia for Postoperative Pain Management After Video-Assisted Thoracoscopic Lobectomy: A Randomized Controlled Trial.

OBJECTIVE: To compare paravertebral block under thoracoscopy with wound infiltration at an early stage after video-assisted thoracic lobectomy surgery. DESIGN: A prospective, randomized, triple-blinded, placebo-controlled trial. SETTING: A single-center university hospital. PARTICIPANTS: Patients scheduled for video-assisted thoracic lobectomy surgery between February 20, 2014 and June 1, 2014 randomly were allocated into paravertebral block (PVB) (n = 35) and infiltration (n = 35) groups. INTERVENTIONS: In the PVB group, 0.5% ropivacaine was injected into the paravertebral space by the surgeon under direct vision with placebo infiltration of saline in the wounds. In the infiltration group, the wounds were infiltrated with 0.5% ropivacaine by the surgeon with a placebo paravertebral block. Subsequently, patient-controlled intravenous morphine analgesia and paracoxib were administered. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were visual analog scale (VAS) pain scores at rest and on cough 0, 2, 6, and 24 hours after surgery. The secondary endpoints were the total morphine during postoperative 0 hours to 24 hours, adverse events, and patient satisfaction with the analgesia. Sixty-one patients completed the study. VAS score on cough at each time point was significantly lower (p<0.05) and median (25th, 75th) morphine consumption was lower in the PVB group than in the infiltration group (26 [10, 35] mg and 42 [29, 58] mg, p<0.001, respectively). There was no difference in VAS score at rest. Patients in the PVB group had higher satisfaction with analgesia than in the infiltration group (p = 0.003). CONCLUSIONS: As part of the multimodal postoperative analgesia, intraoperative paravertebral block provided better dynamic pain relief and reduced morphine consumption compared with local wound infiltration.

Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and ketamine-induced neuroprotection against cerebral ischemic injuries of mice.

Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.