Moteshakereh Seyed Mohammadmisagh, Nikoohemmat Mohammad, Farmani Danial, Khosrowabadi Elahe, Salehi Sakineh, Haghparast Abbas
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuropeptides. 2023 Apr;98:102323. doi: 10.1016/j.npep.2023.102323. Epub 2023 Jan 28.
Stress suppresses the sense of pain, a physiological phenomenon known as stress-induced analgesia (SIA). Brain orexin peptides regulate many physiological functions, including wakefulness and nociception. The contribution of the orexinergic system within the nucleus accumbens (NAc) in the modulation of antinociception induced by forced swim stress (FSS) remains unclear. The present study addressed the role of intra-accumbal orexin receptors in the antinociceptive responses induced by FSS during the persistent inflammatory pain model in the rat. Stereotaxic surgery was performed unilaterally on 106 adult male Wistar rats weighing 250-305 g. Different doses (1, 3, 10, and 30 nmol/ 0.5 μl DMSO) of orexin-1 receptor (OX1r) antagonist (SB334867) or OX2 receptor antagonist (TCS OX2 29) were administered into the NAc five minutes before exposure to FSS for a 6-min period. The formalin test was carried out using formalin injection (50 μl; 2.5%) into the rat's hind paw plantar surface, which induces biphasic pain-related responses. The first phase begins immediately after formalin infusion and takes 3-5 min. Subsequently, the late phase begins 15-20 min after formalin injection and takes 20-40 min. The findings demonstrated that intra-accumbal microinjection of SB334867 or TCS OX2 29 attenuated the FSS-induced antinociception in both phases of the formalin test, with the TCS OX2 29 showing higher potency. Moreover, the effect of TCS OX2 29 was more significant during the early phase of the formalin test. The results suggest that OX1 and OX2 receptors in the NAc might modulate the antinociceptive responses induced by the FSS.
应激会抑制痛觉，这是一种被称为应激诱导镇痛（SIA）的生理现象。脑内食欲素肽调节多种生理功能，包括清醒和痛觉感受。伏隔核（NAc）内的食欲素能系统在强迫游泳应激（FSS）诱导的抗伤害感受调节中的作用尚不清楚。本研究探讨了在大鼠持续性炎症性疼痛模型中，伏隔核内食欲素受体在FSS诱导的抗伤害感受反应中的作用。对106只体重250 - 305克的成年雄性Wistar大鼠进行单侧立体定向手术。在暴露于FSS 6分钟前5分钟，将不同剂量（1、3、10和30 nmol/0.5 μl二甲基亚砜）的食欲素-1受体（OX1r）拮抗剂（SB334867）或OX2受体拮抗剂（TCS OX2 29）注入NAc。使用福尔马林（50 μl；2.5%）注射到大鼠后爪足底表面进行福尔马林试验，该试验会诱发双相疼痛相关反应。第一阶段在福尔马林注入后立即开始，持续3 - 5分钟。随后，第二阶段在福尔马林注射后15 - 20分钟开始，持续20 - 40分钟。研究结果表明，在福尔马林试验的两个阶段，向伏隔核内微量注射SB334867或TCS OX2 29均可减弱FSS诱导的抗伤害感受，其中TCS OX2 29的效力更高。此外，TCS OX2 29在福尔马林试验早期的作用更显著。结果表明，NAc中的OX1和OX2受体可能调节FSS诱导的抗伤害感受反应。
