Department of Animal Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran.
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Eur J Pain. 2021 Nov;25(10):2266-2277. doi: 10.1002/ejp.1840. Epub 2021 Jul 27.
Exposure to stressful experiences is often accompanied by suppressing pain perception, referred to as stress-induced analgesia. The neuropeptides orexins are essential in regulating the mechanism that responds to stressful and painful stimuli. Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. This study aimed to investigate the role of intra-VTA administration of orexin receptor antagonists on stress-induced antinociceptive responses in the animal model of acute pain.
Ninety-three adult Wistar rats weighing 230-250 g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10 and 30 nM/0.3 μl) of SB334867 as the orexin-1 receptor antagonist and TCS OX2 29 as the orexin-2 receptor antagonist into the VTA, just 5 min before 6 min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail-flick test as a model of acute pain.
The results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra-VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail-flick test.
The findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviours induced by FSS in part.
Acute exposure to physical stress suppresses pain-related behaviors in the animal model of acute pain. Blockade of the OX1 and OX2 receptors in the VTA attenuates antinociceptive responses induced by FSS. The contribution of the OX2 receptors in the VTA is more predominant than OX1 receptors in stress-induced analgesia.
暴露于应激体验通常伴随着疼痛感知的抑制，称为应激诱导镇痛。神经肽食欲素在调节对应激和疼痛刺激的机制中是必不可少的。同时，腹侧被盖区（VTA）作为下行疼痛抑制系统的一部分，对伤害性刺激做出反应。本研究旨在探讨 VTA 内给予食欲素受体拮抗剂对急性疼痛动物模型中应激诱导镇痛反应的作用。
93 只体重 230-250 克的成年 Wistar 大鼠单侧植入 VTA 上方的导管。动物在暴露于强迫游泳应激（FSS）前 5 分钟，预先用不同剂量（1、3、10 和 30 nM/0.3 μl）的 SB334867（食欲素-1 受体拮抗剂）和 TCS OX2 29（食欲素-2 受体拮抗剂）预处理，进入 VTA。使用尾部闪烁测试作为急性疼痛模型来测量痛觉阈值。
结果表明，暴露于 FSS 可显著增加镇痛反应。此外，VTA 内给予 SB334768 和 TCS OX2 29 阻断了尾部闪烁测试中 FSS 的镇痛作用。
研究结果表明，VTA 中的 OX1 和 OX2 受体可能部分调节 FSS 诱导的镇痛行为。
急性暴露于身体应激会抑制急性疼痛动物模型中的疼痛相关行为。VTA 中的 OX1 和 OX2 受体阻断可减弱 FSS 诱导的镇痛反应。VTA 中的 OX2 受体的贡献比 OX1 受体在应激诱导镇痛中更为突出。
