Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Science.
School of Medicine, Iran University of Medical Sciences.
Behav Pharmacol. 2024 Aug 1;35(5):253-262. doi: 10.1097/FBP.0000000000000782. Epub 2024 Jun 11.
Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing of dopamine neurons. Besides, sensitive and advanced research techniques led to the recognition of the mesohippocampal dopaminergic terminals, particularly in the hippocampal dentate gyrus (DG). Moreover, previous studies have shown that dopamine receptors within the hippocampal DG play a critical role in induced antinociceptive responses by forced swim stress (FSS) in the presence of inflammatory pain. Since different pain states can trigger various mechanisms and transmitter systems, the present experiments aimed to investigate whether dopaminergic receptors within the DG have the same role in the presence of acute thermal pain.
Ninety-seven adult male albino Wistar rats underwent stereotaxic surgery, and a stainless steel guide cannula was unilaterally implanted 1 mm above the DG. Different doses of SCH23390 or sulpiride as D1- and D2-like dopamine receptor antagonists were microinjected into the DG 5-10 min before exposure to FSS, and 5 min after FSS exposure, the tail-flick test evaluated the effect of stress on the nociceptive response at the time-set intervals.
The results demonstrated that exposure to FSS could significantly increase the acute pain perception threshold, while intra-DG administration of SCH23390 and sulpiride reduced the antinociceptive effect of FSS in the tail-flick test.
Additionally, it seems the D2-like dopamine receptor within the DG plays a more prominent role in FSS-induced analgesia in the acute pain model.
急性应激作为一种应对厌恶刺激的保护机制,通常伴随着通过促进多巴胺神经元的一致爆发来抑制疼痛感知。此外,敏感和先进的研究技术使得中脑海马多巴胺能末梢,特别是海马齿状回(DG)的认识成为可能。此外,先前的研究表明,海马 DG 内的多巴胺受体在存在炎症性疼痛的情况下,通过强制游泳应激(FSS)诱导的抗伤害性反应中发挥关键作用。由于不同的疼痛状态可以触发各种机制和递质系统,本实验旨在研究 DG 内的多巴胺受体在急性热痛存在时是否具有相同的作用。
97 只成年雄性白化 Wistar 大鼠接受立体定向手术,在 DG 上方 1mm 处单侧植入不锈钢引导套管。在暴露于 FSS 之前 5-10 分钟,将不同剂量的 SCH23390 或 sulpiride(D1-和 D2 样多巴胺受体拮抗剂)微注射到 DG 中,在 FSS 暴露后 5 分钟,通过尾巴拍打测试评估应激对设定时间间隔内伤害性反应的影响。
结果表明,暴露于 FSS 可显著增加急性疼痛感知阈值,而 DG 内给予 SCH23390 和 sulpiride 可降低尾巴拍打测试中 FSS 的抗伤害作用。
此外,DG 内的 D2 样多巴胺受体似乎在急性疼痛模型中 FSS 诱导的镇痛中发挥更重要的作用。