背景:已发现腹外侧眶皮质(VLO)在神经性疼痛(NPP)的调节中起重要作用。作为传统的情绪稳定剂,丙戊酸(VPA)目前用于NPP的治疗。然而,VPA是否在VLO中起镇痛作用尚不清楚.
目的:阐明VPA显微注射VLO对备用神经损伤(SNI)的潜在镇痛机制,NPP的动物模型。
方法:我们首先通过腹膜内和VLO内注射来研究VPA的作用。然后,我们通过VLO内注射丁酸钠获得了其作为组蛋白脱乙酰酶抑制剂的作用。最后,GABA能机制是通过VLO内微量注射各种GABA能受体亚型的几种激动剂和拮抗剂来测定的.
结果:腹膜内和VLO内注射VPA均可减轻SNI诱导的机械性异常性疼痛。丁酸钠的显微注射,组蛋白脱乙酰酶抑制剂之一,进入VLO减弱了机械性异常性疼痛。此外,微量注射丙氨,VPA的衍生物是GABA能激动剂,进入VLO也减轻了异常性疼痛。此外,微毒素的显微注射,一种GABAA受体拮抗剂,进入VLO减轻了机械性异常性疼痛;在VPA进入VLO之前,微毒素的显微注射增加了VPA诱导的抗异常性疼痛。此外,显微注射GABAB受体拮抗剂CGP35348,进入VLO减轻了异常性疼痛;在VPA进入VLO之前将CGP35348显微注射也增加了VPA诱导的抗异常性疼痛。更重要的是,咪唑-4-乙酸(I4AA)的显微注射,GABAC受体拮抗剂,进入VLO可增强异常性疼痛;在VPA进入VLO之前将I4AA显微注射可降低VPA诱导的抗异常性疼痛。
结论:这些结果表明组蛋白乙酰化机制和GABA能系统都参与介导VLO诱导的抗超敏反应。
BACKGROUND: 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.
OBJECTIVE: 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.