Systemic administration of the dietary constituent, resveratrol, was previously shown to inhibit the nociceptive jaw-opening reflex (JOR) via the endogenous opioid system. The present study investigated whether resveratrol could similarly affect the JOR under in vivo conditions via 5 H T3 receptor-mediated GABAergic inhibition. We used electrical stimulation of the tongue in pentobarbital-anesthetized rats to evoke the JOR, which was recorded as the anterior belly of the digastric muscle electromyograms (dEMG). Intravenous administration of resveratrol (2 mg/kg) reduced the dEMG amplitude in response to three times the determined threshold electrical stimulation, with maximum inhibition reached within approximately 10 min. These inhibitory effects on the JOR were reversible to control levels after approximately 20 min. Pretreatment of rats with either 5 H T3 receptor antagonist, ondansetron (0.25-1 mg/kg, i.p.), or GABAA receptor antagonist, bicuculline (0.5-1 mg/kg, i.p.), significantly and dose-dependently attenuated the inhibitory effects of resveratrol on dEMG amplitude compared with untreated controls. These findings suggest that resveratrol also attenuates the nociceptive JOR via 5 H T3 receptor-mediated GABAergic inhibition. The present study therefore provides new insight into a possible mechanism underlying resveratrol-induced trigeminal antinociception via the descending pain control system and highlights a potential therapeutic agent for complementary alternative medicine.

中文翻译：

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白藜芦醇通过 5HT3 受体介导的 GABA 能抑制抑制伤害性张开颌反射

此前研究表明，饮食成分白藜芦醇的全身给药可通过内源性阿片类药物系统抑制伤害性下颌张开反射 (JOR)。本研究调查了白藜芦醇是否可以通过 5 H T3 受体介导的 GABA 能抑制在体内条件下类似地影响 JOR。我们在戊巴比妥麻醉的大鼠中使用舌头的电刺激来唤起 JOR，它被记录为二腹肌肌电图 (dEMG) 的前腹部。静脉注射白藜芦醇 (2 mg/kg) 可降低 dEMG 幅度，以响应确定的阈值电刺激的三倍，在大约 10 分钟内达到最大抑制。这些对 JOR 的抑制作用在大约 20 分钟后可逆到对照水平。用 5 H T3 受体拮抗剂昂丹司琼（0.25-1 mg/kg，ip）或 GABAA 受体拮抗剂荷包牡丹碱（0.5-1 mg/kg，ip）预处理大鼠，显着且剂量依赖性地减弱了抑制作用与未处理的对照相比，白藜芦醇的 dEMG 振幅。这些发现表明，白藜芦醇还通过 5 H T3 受体介导的 GABA 能抑制来减弱伤害性 JOR。因此，本研究通过下行疼痛控制系统为白藜芦醇诱导的三叉神经镇痛的可能机制提供了新的见解，并突出了补充替代医学的潜在治疗剂。与未处理的对照相比，显着且剂量依赖性地减弱了白藜芦醇对 dEMG 振幅的抑制作用。这些发现表明，白藜芦醇还通过 5 H T3 受体介导的 GABA 能抑制来减弱伤害性 JOR。因此，本研究通过下行疼痛控制系统为白藜芦醇诱导的三叉神经镇痛的可能机制提供了新的见解，并突出了补充替代医学的潜在治疗剂。与未处理的对照相比，显着且剂量依赖性地减弱了白藜芦醇对 dEMG 振幅的抑制作用。这些发现表明，白藜芦醇还通过 5 H T3 受体介导的 GABA 能抑制来减弱伤害性 JOR。因此，本研究通过下行疼痛控制系统为白藜芦醇诱导的三叉神经镇痛的可能机制提供了新的见解，并突出了补充替代医学的潜在治疗剂。