[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Study on ceramide modulates EAAT-2 participation in the immunoinflammatory response in schizophrenia.

OBJECTIVE: Abnormal immunoinflammatory responses play important roles in the pathogenesis of schizophrenia, but the underlying molecular mechanisms are still unclear. MATERIALS AND METHODS: In this study, the ceramide agonist daunorubicin (DNR) was injected into the lateral ventricles to induce ceramide accumulation. The behavioral tests were used to observe schizophrenia-like behavioral changes. Changes in the mRNA levels of the proinflammatory cytokines and the protein levels of the glutamate transporter excitatory amino acid transporter-2 (EAAT-2) were detected. After inhibition of nuclear factor-κB (NF-κB), the above indices were detected again. Nissl staining was used to assess neuronal damage. RESULTS: After intracerebroventricular injection of DNR, ceramide significantly accumulated in the hippocampus, and behavioral tests revealed negative schizophrenia symptoms accompanied by induced learning and memory dysfunction. Furthermore, the hippocampus demonstrated increased mRNA levels of the proinflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) and significantly decreased EAAT-2 protein levels. Nissl staining revealed neuronal damage after ceramide accumulation. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) reduced the behavioral abnormalities caused by ceramide accumulation, downregulated CONCLUSIONS: The experimental results suggest that ceramide reduces EAAT-2 expression through the NF-κB/TNF-α pathway and causes neuronal excitotoxicity in the pathogenesis of schizophrenia, leading to neuronal damage.