| Background: Basically, patients who need sugurical treatment suffer from great stress. Any adverse events from medical treatment will burden the patients. All the negative emotions such as anxiety and/or depression will slow the patients’ recovery and make their medical experience worse. Ropivacaine(Ropi) is one of the newest amino-amide local anesthetics(LAs) with favorable safety profile compared with the others, however, serious convulsion, which is generally caused by over-dose and/or accidental intravascular injection, and relative negative emotions, such as anxiety or depression, are usually reported. Currently, midazolam is a classic sedative agent for preventing LA-induced convulsion, however, respiratory depression is the fatal complication, especially in the cases of repeated, large dose, and/or rapid intravenous administration. Although dexmedetomine(Dex), a highly selective α2-adrenergic receptors agonist with extremely low risk of respiratory depression, has been world widely used during peri-operation for sedation, analgesia, and organ protection, there is no experimental or clinical evidence concerning the preventive effect of Dex premedication on Ropi-induced convulsion and negative emotions, and also far from being revealed about the underlying mechanisms.Objective: To investigate the effect of different doses of dexmedetomidine pretreatment on ropivacaine-induced convulsion and negative emotions, as well as the expression of phosphorylated-extracellular signal-regulated kinase(p-ERK) in the amygdala mice.Methods: In the current study, we investigated the effects of increasing doses of Dex premedication on 50% convulsive dose(CD50) of Ropi by using a pharmacological approach according to convulsion score. With increasing doses of intraperitoneal(i.p.) Dex 10 min prior to each i.p. RopiCD50, the latency and duration of convulsion were recorded. Open field(OF) and elevated plus maze(EPM) test were used to identify the negative emotions on 24 h, and immunohistochemistry and western blot to investigate p-ERK expression in basolateral amygdala(BLA) on 2 h and in central amygdala(Ce A) on 24 h after convulsion in mice.Results: We observed that the 2.4, 4.8, and 9.6 μg/kg Dex dose-dependently(i) increased 21.72%, 25.70%, and 41.98% of RopiCD50, respectively,(ii) prolonged the latency(Saline-52.29 Ropi vs. 2.4 Dex-63.65 Ropi vs. 4.8 Dex-65.73 Ropi vs. 9.6 Dex-74.24 Ropi: 2.32 ± 0.67 min vs. 3.24 ± 0.74 min vs. 5.98 ± 1.67 min vs. 10.50 ± 1.52 min, P < 0.001) and shortened the duration(Saline-52.29 Ropi vs. 2.4 Dex-63.65 Ropi vs. 4.8 Dex-65.73 Ropi vs. 9.6 Dex-74.24 Ropi: 16.14 ± 2.48 min vs. 12.24 ± 2.33 min vs. 9.52 ± 2.40 min vs. 5.79 ± 0.93 min, P < 0.001) of each Ropi CD50-induced convulsion,(iii) improved the negative emotions indicated by both OF(center time%: Saline-52.29 Ropi vs. 2.4 Dex-63.65 Ropi vs. 4.8 Dex-65.73 Ropi vs. 9.6 Dex-74.24 Ropi: 3.42 ± 0.12% vs. 4.16 ± 0.79% vs. 5.75 ± 0.67% vs. 8.41 ± 0.84%, P < 0.001) and EPM test(OA Time%: Saline-52.29 Ropi vs. 2.4 Dex-63.65 Ropi vs. 4.8 Dex-65.73 Ropi vs. 9.6 Dex-74.24 Ropi: 15.08 ± 1.74% vs. 16.17 ± 2.02 % vs. 18.92 ± 2.40% vs. 22.58 ± 2.33%, P < 0.001; OA Entries%: Saline-52.29 Ropi vs. 2.4 Dex-63.65 Ropi vs. 4.8 Dex-65.73 Ropi vs. 9.6 Dex-74.24 Ropi: 20.83 ± 3.06% vs. 23.33 ± 3.50% vs. 31.67 ± 2.66% vs. 34.00 ± 4.10%, P < 0.001) on 24 h, and(iv) inhibited p-ERK expression in BLA on 2 h and Ce A on 24 h, respectively, indicated by both immunohistochemistry and western blot after each RopiCD50-induced convulsion.Conclusion: Our findings suggest that Dex premedication dose-dependently attenuates Ropi-induced convulsion and negative emotions, which might be via inhibiting p-ERK over-expression in BLA and Ce A, respectively. |
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