Neuropathic pain is a kind of chronic pain that is triggered or caused primarily by damage to the nervous system and neurological dysfunction. It’s known that dexmedetomidine is a new type of highly selective alpha2-adrenoceptor agonist with sedation, anti-anxiety, analgesic and other effects. However, the function and mechanism of dexmedetomidine on neuropathic pain are not clear. Rat DRG neurons were isolated and identified using immunofluorescence assay. Following treatment with H2O2, dexmedetomidine or ROS inhibitor (NAC), the apoptosis and ROS levels were examined by flow cytometery; apoptosis- and anaerobic glycolysis-related proteins were determined by Western blot assay; glucose consumption, pyruvic acid, lactic acid and ATP/ADP ratios were also measured. The results revealed that dexmedetomidine inhibited H2O2-induced apoptosis and reactive oxygen species (ROS) in rat DRG neurons and in addition, dexmedetomidine down-regulated the expression levels of anaerobic glycolysis-related proteins, significantly reduced glucose, pyruvic acid and lactic acid levels. It also increased the ATP/ADP ratio in H2O2-treated rat dorsal root ganglion (DRG) neurons. Moreover, we also demonstrated that ROS inhibitor (NAC) also inhibited H2O2-induced apoptosis and anaerobic glycolysis in rat DRG neurons. In conclusion, dexmedetomidine suppressed H2O2-induced apoptosis and anaerobic glycolysis activity by inhibiting ROS, in rat DRG neurons. Therefore, dexmedetomidine might play a pivotal role in neuropathic pain by the inhibition of ROS.
Patients with orthotopic liver transplantation (OLT) frequently develop acute gut injury (AGI), and dexmedetomidine (Dex) has been reported to exert a protective effect against AGI. We investigated whether Dex protects against AGI through antioxidative stress effects by the Nrf2/HO-1 antioxidative signaling pathway. Rats were randomly allocated into a sham group and six orthotopic autologous liver transplantation (OALT) groups receiving different doses of Dex together with/without α2-adrenergic receptor (AR) blockers. Intestinal tissues were collected to visualize the barrier damage and to measure the indexes of oxidative stress. For in vitro studies, rat intestinal recess epithelial cells (IEC-6) underwent hypoxia/reoxygenation (H/R), and the protective role of Dex was evaluated after α2A-AR siRNA silencing. OALT resulted in increased oxidative stress, significant intestinal injury, and barrier dysfunction. Dex attenuated OALT-induced oxidative stress and intestinal injury, which was abolished by the pretreatment with the nonspecific α2A-AR siRNA blocker atipamezole and the specific α2A-AR siRNA blocker BRL-44408, but not by the specific 2B/C-AR siRNA blocker ARC239. Silencing of α2A-AR siRNA also attenuated the protective role of Dex on alleviating oxidative stress in IEC-6 cells subjected to H/R. Dex exerted its protective effects by activating Nrf2/HO-1 antioxidative signaling. Collectively, Dex attenuates OALT-induced AGI via α2A-AR-dependent suppression of oxidative stress, which might be a novel potential therapeutic target for OALT-induced AGI.
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The relationships between the temporal focus of mind-wandering (i.e., past-oriented and future-oriented mind-wandering) and well-being are important issues for adolescents, which may have significant implications on their well-being and self-identity development. However, few studies tested the temporal focus of mind-wandering and its emotional consequences in adolescents. In the present study, we conducted two studies using self-reported questionnaires from large sample sets to examine the relationships between the temporal focus of mind-wandering and hedonic (pleasure attainment) and eudaimonic (meaning pursuing) well-being among Chinese adolescents. Study 1 preliminarily tested the relationships between the temporal focus of mind-wandering and hedonic well-being among adolescents ( n = 1273) suggesting that both past-oriented mind-wandering (PMW) and future-oriented mind-wandering (FMW) were positively correlated with hedonic well-being. Study 2 used a new sample ( n = 986) and included another aspect of well-being (i.e., eudaimonic well-being), showing that PMW and FMW were both positively correlated with hedonic and eudaimonic well-being. Moreover, self-reflection mediated the relationships between FMW and hedonic/eudaimonic well-being, whereas self-reflection did not act as a mediator in the relationships between PMW and well-being. The present findings indicated that both PMW and FMW are beneficial for Chinese adolescents’ well-being, and emphasized the mediating role of self-reflection in the relationships between FMW and well-being.
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