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.

压力会抑制痛觉，这是一种称为压力诱导镇痛 (SIA) 的生理现象。脑食欲肽调节许多生理功能，包括觉醒和伤害感受。伏隔核 (NAc) 内的食欲素系统在调节由强迫游泳应激 (FSS) 诱导的抗伤害感受中的作用仍不清楚。本研究探讨了在大鼠持续性炎症疼痛模型中，伏隔内食欲素受体在 FSS 诱导的镇痛反应中的作用。对 106 只体重 250–305 g 的成年雄性 Wistar 大鼠单侧进行立体定向手术。不同剂量（1、3、10 和 30 nmol/ 0. 在暴露于 FSS 6 分钟之前，将 5 μl DMSO）的食欲素-1 受体（OX1r）拮抗剂（SB334867）或 OX2 受体拮抗剂（TCS OX2 29）施用到 NAc 中 5 分钟。使用福尔马林注射液（50 μl；2.5%）到大鼠后爪足底表面进行福尔马林试验，这会引起双相疼痛相关反应。第一阶段在福尔马林输注后立即开始，持续 3-5 分钟。随后，晚期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，SB334867 或 TCS OX2 29 的颅内显微注射在福尔马林试验的两个阶段减弱了 FSS 诱导的抗伤害作用，其中 TCS OX2 29 显示出更高的效力。此外，TCS OX2 29 的效果在福尔马林试验的早期阶段更为显着。