Experimental Biology Centre (NUBEX), University of Fortaleza (UNIFOR), Brazil; Faculty of Dentistry, University of Toronto, Canada.
Faculty of Dentistry, University of Toronto, Canada.
Life Sci. 2019 Jun 15;227:122-128. doi: 10.1016/j.lfs.2019.04.032. Epub 2019 Apr 16.
UNLABELLED: Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain. AIMS: This study aimed to examine whether (-)-α-bisabolol (BISA), a natural terpene, can attenuate nociceptive behaviour and central sensitisation in a rodent model of trigeminal neuropathic pain. MATERIALS AND METHODS: Infraorbital nerve transection (IONX) or sham operation was performed in adult male rats. Head withdrawal thresholds as a measure of facial mechanical sensitivity were tested with von Frey monofilaments applied bilaterally to the facial vibrissal pad pre-operatively (baseline) and then post-operatively before and at 60, 120, 240 and 360 min after administration of vehicle control per oris (p.o.) or BISA (200 mg/kg p.o.) (n = 8/group). Effects of BISA or vehicle on the activity of nociceptive neurons recorded in the medullary dorsal horn (MDH) were tested on post - operative day 8-10. ANOVA followed by post-hoc Bonferroni tested for statistically significant differences (p < 0.05) across study groups and time points. KEY FINDINGS: IONX animals (but not sham or naïve animals) showed post-operative facial mechanical hypersensitivity that was unaffected by vehicle. However, administration of BISA at post-operative day 7 significantly reversed the mechanical hypersensitivity in IONX rats; this effect lasted for at least 6 h. BISA also attenuated IONX-induced central sensitisation of MDH nociceptive neurons, as reflected in reversal of their reduced activation thresholds, increased responses to graded mechanical stimuli and enhanced spontaneous activity. SIGNIFICANCE: BISA may attenuate nociceptive behaviour and central sensitisation in a rat model of acute trigeminal neuropathic pain.
目的:本研究旨在探讨天然萜烯(-)-α- 姜黄烯(BISA)是否能减轻三叉神经病理性疼痛模型中啮齿动物的伤害性行为和中枢敏化。
材料和方法:对成年雄性大鼠进行眶下神经横断(IONX)或假手术。使用 von Frey 单丝双侧施加到面部触须垫,在术前(基线)和术后之前以及术后 60、120、240 和 360 分钟后,经口(p.o.)给予载体对照物或 BISA(200mg/kg p.o.)时,测试头撤回阈值作为面部机械敏感性的测量指标(n=8/组)。在术后第 8-10 天测试 BISA 或载体对记录在延髓背角(MDH)中的伤害性神经元活性的影响。使用 ANOVA 并进行事后 Bonferroni 检验,以检验各研究组和时间点之间的统计学差异(p<0.05)。
主要发现:IONX 动物(而非假手术或未处理动物)表现出术后面部机械性超敏反应,而载体对此无影响。然而,在术后第 7 天给予 BISA 可显著逆转 IONX 大鼠的机械性超敏反应;这种作用至少持续 6 小时。BISA 还减轻了 IONX 诱导的 MDH 伤害性神经元的中枢敏化,反映在其激活阈值降低、对分级机械刺激的反应增加以及自发性活动增强的逆转。
意义:BISA 可能会减轻急性三叉神经病理性疼痛模型中啮齿动物的伤害性行为和中枢敏化。
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