Dezfouli Ramin Abdi, Mazaheri Sajad, Mousavi Zahra, Haghparast Abbas
Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Behav Brain Res. 2023 Apr 12;443:114307. doi: 10.1016/j.bbr.2023.114307. Epub 2023 Feb 8.
It has been declared that dopamine receptors within the hippocampal formation are involved in emotion, memory, and pain processing. Remarkably, both CA1 and dentate gyrus (DG) areas of the hippocampal formation are involved in persistent peripheral nociceptive perception. A prior study showed that dopamine receptors within the hippocampal DG have a critical role in antinociception induced by forced swim stress (FSS), as a physical stressor, in the presence of formalin irritation. The present experiments were designed to assess whether dopaminergic receptors within the CA1 have any role in antinociceptive responses induced by restraint stress (RS) as a psychological stressor after applying the formalin test as an animal model of persistent inflammatory pain. The D1- and D2-like dopamine receptor antagonists, SCH23390 and Sulpiride (0.25, 1, and 4 μg/0.5 μl), were injected into the CA1 areas of ninety-six male albino Wistar rats 5 min before a 3-h period of restraint stress. Ten min after stress termination, a 50-μl formalin 2.5 % was subcutaneously injected into the plantar surface of the rat's hind paw to induce persistent inflammatory pain. Nociceptive behaviors in both phases of the formalin test were analyzed in the 5-min blocks for a 60-min period. The obtained results demonstrate that although RS could induce an antinociceptive response in both phases of the formalin test, microinjection of D1- and D2-like dopamine receptors, antagonists attenuated RS-induced analgesia. These results support the hypothesis that acute restraint stress could induce analgesia via dopaminergic projection to the CA1 region of the hippocampal formation.
已声明海马结构内的多巴胺受体参与情绪、记忆和疼痛处理。值得注意的是，海马结构的CA1区和齿状回（DG）均参与持续性外周伤害性感受。先前的一项研究表明，在福尔马林刺激存在的情况下，作为一种物理应激源，海马DG内的多巴胺受体在强迫游泳应激（FSS）诱导的抗伤害感受中起关键作用。本实验旨在评估在将福尔马林试验作为持续性炎性疼痛的动物模型应用后，作为心理应激源的束缚应激（RS）诱导的抗伤害感受反应中，CA1内的多巴胺能受体是否起作用。在3小时的束缚应激前5分钟，将D1和D2样多巴胺受体拮抗剂SCH23390和舒必利（0.25、1和4μg/0.5μl）注射到96只雄性白化Wistar大鼠的CA1区。应激终止10分钟后，将50μl 2.5%的福尔马林皮下注射到大鼠后爪的足底表面，以诱导持续性炎性疼痛。在60分钟内，以5分钟为间隔分析福尔马林试验两个阶段的伤害性感受行为。所得结果表明，尽管RS可在福尔马林试验的两个阶段诱导抗伤害感受反应，但D1和D2样多巴胺受体拮抗剂的微量注射减弱了RS诱导的镇痛作用。这些结果支持以下假设：急性束缚应激可通过向海马结构CA1区的多巴胺能投射诱导镇痛。
