向大鼠的眶腹外侧皮质微注射丙戊酸可产生抗伤害感受作用。
Microinjection of valproic acid into the ventrolateral orbital cortex exerts an antinociceptive effect in a rat of neuropathic pain.
机构信息
College of Medicine and Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
Department of Pharmacology and Toxicology, Institute of Basic Medicine Science, Xi'an Medical University, Xi'an, Shaanxi, People's Republic of China.
出版信息
Psychopharmacology (Berl). 2020 Aug;237(8):2509-2516. doi: 10.1007/s00213-020-05551-7. Epub 2020 May 28.
RATIONALE
Ventrolateral orbital cortex (VLO) has been found to play an important role in the regulation of neuropathic pain (NPP). As a traditional mood stabilizer, valproic acid (VPA) is currently employed in the treatment of NPP. However, whether VPA plays an analgesic role in VLO is still unknown.
OBJECTIVES
To elucidate the underlying analgesic mechanism of microinjection of VPA into the VLO on spared nerve injury (SNI), an animal model of NPP.
METHODS
We firstly examined the role of VPA by intraperitoneal and intral-VLO injection. Then, we accessed its role as a histone deacetylase inhibitor by intral-VLO microinjection of sodium butyrate. Finally, the GABAergic mechanism was measured through the intra-VLO microinjection of several agonists and antagonists of various GABAergic receptor subtypes.
RESULTS
Both intraperitoneal and intral-VLO injection of VPA attenuated SNI-induced mechanical allodynia. Microinjection of sodium butyrate, one of the histone deacetylase inhibitors, into the VLO attenuated the mechanical allodynia. Besides, microinjection of valpromide, a derivative of VPA which is a GABAergic agonist, into the VLO also attenuated allodynia. Furthermore, microinjection of picrotoxin, a GABAA receptor antagonist, into the VLO attenuated mechanical allodynia; microinjection of picrotoxin before VPA into the VLO increased VPA-induced anti-allodynia. Besides, microinjection of CGP 35348, a GABAB receptor antagonist, into the VLO attenuated allodynia; microinjection of CGP 35348 before VPA into the VLO also increased VPA-induced anti-allodynia. What is more, microinjection of imidazole-4-acetic acid (I4AA), a GABAC receptor antagonist, into the VLO enhanced allodynia; microinjection of I4AA before VPA into the VLO decreased VPA-induced anti-allodynia.
CONCLUSIONS
These results suggest that both the histone acetylation mechanism and GABAergic system are involved in mediating VLO-induced anti-hypersensitivity.
背景
已发现腹外侧眶皮层（VLO）在调节神经性疼痛（NPP）中发挥重要作用。丙戊酸（VPA）作为一种传统的心境稳定剂，目前用于治疗 NPP。然而，VPA 是否在 VLO 中发挥镇痛作用尚不清楚。
目的
阐明 VPA 微注射到 spared nerve injury（SNI），即 NPP 动物模型的 VLO 中产生镇痛作用的潜在机制。
方法
我们首先通过腹腔内和 VLO 内注射来研究 VPA 的作用。然后，我们通过 VLO 内微注射丁酸钠来研究其作为组蛋白去乙酰化酶抑制剂的作用。最后，通过 VLO 内注射几种 GABA 能受体亚型的激动剂和拮抗剂来测量 GABA 能机制。
结果
腹腔内和 VLO 内注射 VPA 均可减轻 SNI 引起的机械性痛觉过敏。VLO 内微注射组蛋白去乙酰化酶抑制剂丁酸钠可减轻机械性痛觉过敏。此外，VPA 的衍生物丙戊酸钠（一种 GABA 能激动剂）微注射到 VLO 中也可减轻痛觉过敏。此外，VLO 内注射 GABAA 受体拮抗剂荷包牡丹碱可减轻机械性痛觉过敏；VPA 注射到 VLO 之前注射荷包牡丹碱增加了 VPA 引起的抗痛觉过敏。此外，VLO 内微注射 GABAB 受体拮抗剂 CGP 35348 可减轻痛觉过敏；VPA 注射到 VLO 之前注射 CGP 35348 也增加了 VPA 引起的抗痛觉过敏。此外，VLO 内注射 GABAC 受体拮抗剂咪唑-4-乙酸（I4AA）可增强痛觉过敏；VPA 注射到 VLO 之前注射 I4AA 降低了 VPA 引起的抗痛觉过敏。
结论
这些结果表明，组蛋白乙酰化机制和 GABA 能系统均参与介导 VLO 诱导的抗敏作用。
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