Paraventricular nucleus-central amygdala oxytocinergic projection modulates pain-related anxiety-like behaviors in mice.

AIMS: Anxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)-central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety-like behaviors induced by inflammatory pain. METHODS: After inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light-dark transition test, and marble burying test to examine the anxiety-like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN-CeA. RESULTS: The key results are as follows: inflammatory pain-induced anxiety-like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain-related anxiety-like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety-like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety-like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVNoxytocin -CeA circuit prevented anxiety-like behavior in response to inflammatory pain. CONCLUSION: The results of our study suggest that oxytocin has anti-anxiety effects and provide novel insights into the role of PVNoxytocin -CeA projections in the regulation of anxiety-like behaviors induced by inflammatory pain.

PTEN inhibitor bisperoxovanadium protects against noise-induced hearing loss.

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.

Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.

Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/κ opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a κ opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in κ opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of κ opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

Optimum interval time of programmed intermittent epidural bolus of ropivacaine 0.08% with sufentanyl 0.3 µg/mL for labor analgesia: a biased-coin up-and-down sequential allocation trial.

BACKGROUND: The programmed intermittent epidural bolus (PIEB) technique is widely used in labor analgesia, but the parameter settings of PIEB have not yet been standardized. We designed a study to identify the optimal interval duration for PIEB using 10 mL of ropivacaine 0.08% and sufentanyl 0.3 µg/mL, a regimen commonly used to control labor pain in China, to provide effective analgesia in 90% of women during the first stage of labor without breakthrough pain. METHODS: We conducted a double-blind sequential allocation trial to obtain the effective interval 90% (EI90%) during the first stage of labor between April 2019 and May 2019. This study included the American Society of Anesthesiologists physical status II-III nulliparous parturients at term, who requested epidural analgesia. The bolus volume was fixed at 10 mL of ropivacaine 0.08% with sufentanyl 0.3 µg/mL. Participants were divided into four groups (groups 60, 50, 40, and 30) according to the PIEB intervals (60, 50, 40, and 30 min, respectively). The interval duration of the first parturient was set at 60 min and that of subsequent parturients varied according to a biased-coin design. The truncated Dixon and Mood method and the isotonic regression analysis method were used to estimate the EI90% and its 95% confidence intervals (CIs). RESULTS: Forty-four women were enrolled in this study. The estimated optimal interval was 44.1 min (95% CI 41.7-46.5 min) and 39.5 min (95% CI 32.5-50.0 min), using the truncated Dixon and Mood method and isotonic regression analysis, respectively. The maximum sensory block level above T6 was in nearly 20% of parturients in group 30; however, 5.3%, 0%, and 0% of the parturients presented with sensory block level above T6 in groups 40, 50, and 60, respectively. There were no cases of hypotension and only one parturient complained of motor block. CONCLUSION: With a fixed 10 mL dose of ropivacaine 0.08% with sufentanyl 0.3 µg/mL, the optimal PIEB interval is about 42 min. Further studies are warranted to define the efficacy of this regimen throughout all stages of labor. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022199; http://www.chictr.org.cn/com/25/historyversionpuben.aspx?regno=ChiCTR1900022199.

Enhanced recovery after cesarean delivery: a challenge for anesthesiologists.

Enhanced recovery after cesarean (ERAC) delivery is an evidence-based, multi-disciplinary approach throughout pre-, intra-, post-operative period. The ultimate goal of ERAC is to enhance recovery and improve the maternal and neonatal outcomes. This review highlights the role of anesthesiologist in ERAC protocols. This review provided a general introduction of ERAC including the purposes and the essential elements of ERAC protocols. The tool used for evaluating the quality of ERAC (ObsQoR-11) was discussed. The role of anesthesiologist in ERAC should cover the areas including management of peri-operative hypotension, prevention and treatment of intra- and post-operative nausea and vomiting, prevention of hypothermia and multi-modal peri-operative pain management, and active pre-operative management of unplanned conversion of labor analgesia to cesarean delivery anesthesia. Although some concerns still remain, ERAC implementation should not be delayed. Regular assessment and process improvement should be imbedded into the protocol. Further high-quality studies are warranted to demonstrate the effectiveness and efficacy of the ERAC protocol.

[A cross-sectional study on the industrial noise over-limit status in Guangzhou factories].

OBJECTIVE: To investigate the industrial noise over-limit status of the worksites in Guangzhou factories, so as to promote the prevention and control of occupational noise hazards. METHODS: 211 factories in Guangzhou were monitored and investigated. The analysis and assessment were developed for the properties and size of the factories, the districts of the factories being located, the industries of the factories being classified and the date of monitoring. RESULTS: In this understudied factories, most of them were national-owned and joint-ventures, medium size, located in urban, and mainly involved in the industries of manufacturing of motor vehicle, shipping, electron and electric equipment, and the industries of petroleum and chemicals. The prevalence of noise over-limit was higher in joint-ventures (36.0%) and private-run enterprises (31.2%). The over-limit status mainly presented in industries of textile, food and beverage processing, and leather producing, with getting prevalence of over-limit 46.7%, 43.1% and 41.3% respectively. Subsequence were industries of manufacturing of electron and electric equipment, motor vehicle and shipping, and industries of printing and goods producing for culture and sports, with the prevalence for all > 35%. Factories monitored during spring and summer also had higher prevalence of noise over-limit. The similar results were got after adjustment for each other using multivariable regression. The most common over-limit sites mainly focused on the operation of cutting and sawing, milling and planing, pressing, riveting, drilling, jointing, assembling and quality inspecting in industries of mechanism processing and manufacturing, on quality inspecting and packing in industries of pharmacy and food and beverage manufacture, on spinning and scutching in textile industry, and on cleaning and maintaining as assistant jobs, and patrolling and inspecting air-press machine, ventilation machine, dynamotor and pump. CONCLUSION: Noise in Guangzhou factories widely exists with different industries and districts. To strengthen noise occupational hazards prevention and control for the high risk districts, industries and worksites should be the key job in the future.

[Measurement and analysis of personal noise exposure in a city metro].

OBJECTIVE: To measure and analyze the personal noise exposure of city metro station workers by using noise dosimeter. METHODS: According to job category and work type, all workers were divided into 4 groups. The workers from each group were selected as subjects for personal noise exposure measurement. CEL-320 dosimeters were worn by each subject and noise data collected by a phone fixed at collar. All subjects were asked to take notes about their working activities when they were wearing CEL-320 dosimeters. Each worker's one workday LAeq, geometric mean and range of each group were computed. RESULTS: There were many noise sources in the metro station, and the noise exposure was unstable. The varieties of personal noise levels were recorded among 48 workers, the highest LAeq work type was of the instrument room, (81.8 +/- 2.5) dB (A), and the biggest LAeq rang was of the hall, 8.1 dB (A). The lowest LAeq was of the station control room (68.7 +/- 1.8) dB (A) and the lowest LAeq rang also was there, 4.0 dB (A). CONCLUSION: The personal noise exposure of metro station should be implicated. Measuring personal noise exposure individually with dosimeters might obtain the noise exposure level more integrally in the complicated environment.