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Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (N 2 O) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of N 2 O remain largely unknown. Neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of N 2 O. In this study, we revealed that repeated N 2 O exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated N 2 O exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of N 2 O were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that N 2 O exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of N 2 O exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of N 2 O.

AimsAnxiety 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.MethodsAfter 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.ResultsThe 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.ConclusionThe 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.

AimsWe compared analgesic outcomes between single-orifice and multiorifice wire-reinforced catheters under 480 mL/hour delivery rate with programmed intermittent epidural bolus administration.MethodsBetween August and November 2021, 182 nulliparous and healthy women with singleton pregnancy, 2–5 cm cervical dilation, and requesting neuraxial analgesia were randomized to receive either single-orifice or multiorifice catheters. Epidural analgesia was initiated and maintained with 0.1% ropivacaine and 0.3 µg/mL sufentanil. Programmed intermittent epidural bolus volume of 10 mL was administered every 45 min at 480 mL/hour beginning immediately after the test dose. Primary outcome was the percentage of parturients in the two groups with adequate analgesia 20 min after the initial bolus.ResultsCompared with multiorifice catheters, single-orifice catheters were associated with a higher proportion of parturients with adequate analgesia (71.8% vs 56.0%, respectively; 95% CI 1.3% to 29%, p=0.03) and more frequent S2sensory blockade (37.6% vs 22.6%, respectively; 95% CI −30% to 1%, p=0.03) 20 min after block initiation. Median time (IQR) to adequate analgesia was 12 (8–30) min and 20 (10–47) min with single-orifice and multiorifice catheters, respectively (95% CI 0.1 to 0.7 min, p<0.01). The median (IQR) ropivacaine consumption per hour was higher in parturients receiving multiorifice catheters than those with single-orifice catheters (15.3 (13.3–17.0) mg/hour vs 13.3 (13.3–15.4) mg/hour, respectively; 95% CI 0.2 to 0.8 mg/hour, p<0.001).ConclusionSingle-orifice catheters used for programmed intermittent epidural bolus at 480 mL/hour for epidural labor analgesia had improved analgesic efficacy than multiorifice catheters.Trial registration numberChiCTR2100049872.