Ansari Sanam, Khahpay Roghaieh, Khakpai Fatemeh, Heidarzadeh Zahra, Khojasteh Seyed Mahdi Banan
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Psychopharmacology (Berl). 2025 Jan;242(1):129-147. doi: 10.1007/s00213-024-06653-2. Epub 2024 Aug 24.
The present study has investigated whether circulating estrogen level variations in the pro-estrus and estrus phases of the intact rats and estrogen depletion in the ovariectomized animals (OVX) adjust the formalin-induced nociceptive behaviors. During the pro-estrus and estrus phases of rats' estrus cycle and in the OVX rats, 17β-estradiol and ICI 182,780 (estrogen receptor antagonist) were administered into the right paragigantocellularis lateralis (LPGi) nucleus. Then, the formalin-induced flexing and licking responses were recorded for 60 min. The findings of this study revealed that intra-LPGi administration of 17β-estradiol (0.8 μmol) reduced the formalin-induced flexing and licking duration in pro-estrus and estrus rats (P < 0.001), suggesting an analgesic effect. 17β-Estradiol injection into the LPGi nucleus of OVX rats increased the flexing duration (P < 0.05) while decreasing the licking duration (P < 0.05) of the formalin test. The pain modulatory effect of 17β-estradiol on the flexing response was reversed by ICI 182,780 (15 nmol) in the pro-estrus (P < 0.001) and estrus rats (P < 0.001) but not in the OVX rats. Also, pretreatment of LPGi nucleus with ICI 182,780 reversed the analgesic effect of 17β-estradiol on the licking response in the pro-estrus (P < 0.05), estrus (P < 0.001), and OVX rats (P < 0.001). These results suggest that the pain threshold in intact female rats is modulated independently of the estrus state. Still, the basal level of plasma estrogen and the activation of its receptors are necessary for pain modulation.
本研究调查了完整大鼠发情前期和发情期循环雌激素水平的变化以及去卵巢动物（OVX）的雌激素耗竭是否会调节福尔马林诱导的伤害性反应行为。在大鼠发情周期的发情前期和发情期以及OVX大鼠中，将17β-雌二醇和ICI 182,780（雌激素受体拮抗剂）注入右侧外侧巨细胞旁核（LPGi）。然后，记录福尔马林诱导的屈曲和舔舐反应60分钟。本研究结果显示，向LPGi内注射17β-雌二醇（0.8μmol）可缩短发情前期和发情期大鼠福尔马林诱导的屈曲和舔舐持续时间（P < 0.001），表明具有镇痛作用。向OVX大鼠的LPGi核内注射17β-雌二醇会增加福尔马林试验的屈曲持续时间（P < 0.05），同时缩短舔舐持续时间（P < 0.05）。在发情前期（P < 0.001）和发情期大鼠（P < 0.001）中，ICI 182,780（15 nmol）可逆转17β-雌二醇对屈曲反应的疼痛调节作用，但在OVX大鼠中则不然。此外，用ICI 182,780预处理LPGi核可逆转17β-雌二醇对发情前期（P < 0.05）、发情期（P < 0.001）和OVX大鼠（P < 0.001）舔舐反应的镇痛作用。这些结果表明，完整雌性大鼠的痛阈调节与发情状态无关。然而，血浆雌激素的基础水平及其受体的激活对于疼痛调节是必要的。
