Tomić Maja A, Pecikoza Uroš B, Micov Ana M, Stepanović-Petrović Radica M
From the Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Anesth Analg. 2015 Dec;121(6):1632-9. doi: 10.1213/ANE.0000000000000953.
Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action.
The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain.
ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner.
ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.
许多难以治疗的临床疼痛状态都具有伤害性感受通路敏化这一共同特征。能够使过度兴奋的神经活动恢复正常的药物（如抗癫痫药物）可能有助于缓解这些疼痛状态。醋酸艾司利卡西平（ESL）是一种源自卡马西平/奥卡西平的新型抗癫痫药物，具有更良好的代谢特征以及潜在更好的耐受性。我们研究了ESL在炎症性疼痛和神经性疼痛模型中的疗效及其作用的潜在机制。
在三叉神经（口面部福尔马林试验）、神经性（链脲佐菌素诱导的糖尿病性神经病变模型）和内脏疼痛（扭体试验）小鼠模型中评估ESL的镇痛作用。在三叉神经疼痛模型中测试5-HT1B/1D 5-羟色胺受体（GR 127935）以及CB1（AM251）和CB2大麻素受体（AM630）拮抗剂对ESL镇痛作用的影响。
在口面部福尔马林试验的第二阶段（P≤0.011）、糖尿病小鼠的甩尾试验（P≤0.013）以及扭体试验（P≤0.003）中，ESL均表现出显著的剂量依赖性镇痛作用。GR 127935（P≤0.038）以及AM251和AM630（两种拮抗剂P均≤0.013）均以剂量相关方式显著抑制ESL的镇痛作用。
ESL在三叉神经、神经性和内脏疼痛模型中均显示出疗效。在三叉神经疼痛模型中，ESL的镇痛作用至少部分是由5-HT1B/1D 5-羟色胺和CB1/CB2大麻素受体介导的。本研究表明ESL可能对炎症性疼痛和神经性疼痛的临床治疗有用。
