Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn.

Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA­374a/forkhead box O1 signaling axis.

Ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (DDP) resistance in ovarian cancer cells. Ovarian cancer cell viability was assessed by the Cell Counting kit­8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)­374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription­quantitative PCR; the binding ability of miR­374a to FOXO1 was assessed by the dual­luciferase reporter assay; cellular sensitivity to DDP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl­2­like­protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased miR­374a expression levels in A2780 cells. In addition, the viability of A2780/DDP cells in the propofol + DDP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR­374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. Conversely, genetic knockdown of miR­374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, miR­374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. In addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. In conclusion, propofol downregulated miR­374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

Antigen retrieval pre-treatment causes a different expression pattern of Cav3.2 in rat and mouse spinal dorsal horn.

Cav3 channels consist of three isoforms, Cav3.1 (α1G), Cav3.2 (α1H), and Cav3.3 (α1I), which produce low-threshold spikes that trigger burst firings in nociceptive neurons of the spinal dorsal horn (SDH) and dorsal root ganglion (DRG). Although Cav3.2 plays a crucial role in pathological pain, its distribution in SDH still remains controversial. One study showed that Cav3.2 is ubiquitously expressed in neurons, but another study implied that Cav3.2 is expressed restricted to astrocytes. To unravel these discrepancies, we used methods of immunohistochemistry either with or without antigen retrieval (AR) pre-treatment to detect Cav3 in SDH and DRG from both rats and mice. Moreover, Cav3.2 mRNA was detected in mice SDH using in situ hybridization. We found that the expression pattern of Cav3.2 but not Cav3.1 and Cav3.3 in SDH were largely different with or without AR pre-treatment, which showed a neuron-like and an astrocyte-like appearance, respectively. Double staining further demonstrated that Cav3.2 was mainly co-stained with the neuronal marker NeuN in the presence of AR but was with glial fibrillary acidic protein (GFAP, marker for astrocytes) in the absence of AR pre-treatment. Importantly, Cav3.2 mRNA was mainly co-localized with Cav3.2 but not GFAP. Together, our findings indicate that AR pre-treatment or not impacts the expression pattern of Cav3.2, which may make a significant contribution to the future study of Cav3.2 in SDH.

Evaluation of acute normovolemic hemodilution in patients undergoing intracranial meningioma resection: A quasi-experimental trial.

The aim of this study was to evaluate the safety of acute normovolemic hemodilution (ANH) for patients undergoing intracranial meningioma resection.Eighty patients (aged 48-65 years) with American Society of Anesthesiologists physical status I-II undergoing intracranial meningioma resection were included in this prospective observational study. The patients were randomly divided into group A (ANH group), which underwent a combination of ANH and intraoperative cell salvage (ICS), and group B (control group), which underwent ICS alone. The study parameters were recorded as baseline values before blood drainage (T0), after blood drainage (T1), and before (T2) and after (T3) retransfusion in group A. Whereas in group B, the same parameters were measured 10 minutes after anesthesia induction (T0), before surgery (T1), and before (T2) and after (T3) transfusion of autologous blood.When intraoperative blood loss was <2000 mL, the mean volume of homologous blood transfused in group A patients was 100.8 ±â€Š82.3 mL, compared with the 190.0 ±â€Š91.8 mL in group B. Reduction in homologous blood used in group A was statistically significant (P < .05). In group B, 15.1% patients received homologous blood, whereas only 5.9% patients received homologous blood in group A. The difference in heart rate between both groups at different time points was statistically nonsignificant (P > .05). The mean hemoglobin and hematocrit levels at T1 and T2 in group A were lower than in group B (P < .05). The prothrombin time and activated partial thromboplastin time in both groups were prolonged significantly after T2 (all P < .05), but were all within normal range. There were no significant differences in postoperative hospital stay, mortality, and postoperative infection between the 2 groups.For patients undergoing excision of intracranial meningioma, ANH is an effective procedure to reduce the need for allogeneic transfusions.