Resveratrol suppresses nociceptive jaw-opening reflex via 5HT3 receptor-mediated GABAergic inhibition

Resveratrol suppresses nociceptive jaw-opening reflex via 5HT3 receptor-mediated GABAergic inhibition
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DOI:
10.1016/j.neures.2019.10.012
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发表时间:
2020-11-01
影响因子:
2.9
通讯作者:
Takeda, Mamoru
Takeda, Mamoru
中科院分区:
医学4区
文献类型:
--
作者:
Hirata, Kounosuke;Nishiki, Yuto;Takeda, Mamoru

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全身给药的饮食成分,白藜芦醇,以前被证明是通过内源性阿片系统抑制伤害性下颌张开反射(JOR)。本研究探讨白藜芦醇是否可以通过抑制5-HT(3)受体介导的GABA能在体内条件下同样影响JOR。我们使用戊巴比妥麻醉大鼠的舌头电刺激诱发JOR,这是记录为二腹肌肌电图(dEMG)的前腹。静脉注射白藜芦醇(2 mg/kg)可降低dEMG振幅,约10 min内达到最大抑制。约20 min后,这些对JOR的抑制作用可逆转至对照水平。或GABA(A)受体拮抗剂荷包牡丹碱(0.5-1 mg/kg,腹膜内),与未处理的对照组相比,显著且剂量依赖性地减弱白藜芦醇对dEMG振幅的抑制作用。这些结果表明,白藜芦醇也通过5 HT(3)受体介导的GABA能抑制来减弱伤害性JOR。因此,本研究提供了新的见解,潜在的机制白藜芦醇诱导的三叉神经镇痛通过下行疼痛控制系统,并强调了一个潜在的治疗剂的补充替代医学。(C)2019 Elsevier B. V.和日本神经科学学会。All rights reserved.
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 5HT(3) 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 5HT(3) receptor antagonist, ondansetron (0.25-1 mg/kg, i.p.), or GABA(A) 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 5HT(3) 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. (C) 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.