Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Steroids. 2012 Feb;77(3):241-9. doi: 10.1016/j.steroids.2011.11.011. Epub 2011 Dec 17.
Although estradiol has been reported to influence pain sensitivity, the role of estriol (an estradiol metabolite and another widely used female sex hormone) remains unclear. In this study, pain behavior tests, whole-cell patch clamp recording and Western blotting were used to determine whether estriol plays a role in pain signal transduction and transmission. Either systemic or local administration of 17β-estradiol produced a significant rise of mechanical pain threshold, while estriol lacked this effect in normal and ovariectomized (OVX) rats following estriol replacement. Local administration of 17β-estradiol or estriol significantly decreased ATP-induced spontaneous hind-paw withdrawal duration (PWD), which was blocked by an estrogen receptor antagonist, ICI 182, 780. However, systemic application of estriol in normal or OVX rats lacked this similar effect. In cultured dorsal root ganglion neurons, estriol attenuated α,β-methylene ATP-induced transient currents which were blocked by ICI 182, 780. In complete Freund's adjuvant treated (CFA) rats, systemic application of 17β-estradiol or estriol decreased the mechanical pain threshold significantly, but did not change the inflammatory process. Similar effects were observed after estriol replacement in OVX rats. The expression of c-fos in lumbosacral spinal cord dorsal horn (SCDH) was increased significantly by administration of 17β-estradiol but not estriol, and not by estriol replacement in OVX rats. These results suggest that 17β-estradiol but not estriol plays an anti-hyperalgesic role in physiological pain. However, both peripheral 17β-estradiol and estriol play anti-hyperalgesic roles in ATP-induced inflammatory pain. Systemic application of estriol as well as 17β-estradiol plays hyperalgesic roles in CFA-induced chronic pain.
尽管已报道雌二醇会影响痛觉敏感性，但雌三醇（一种雌二醇代谢物和另一种广泛使用的女性性激素）的作用仍不清楚。在这项研究中，使用痛觉行为测试、全细胞膜片钳记录和 Western blot 确定雌三醇是否在痛觉信号转导和传递中发挥作用。全身或局部给予 17β-雌二醇可显著提高机械性痛觉阈值，而在雌三醇替代治疗后，正常和卵巢切除（OVX）大鼠中雌三醇缺乏这种作用。局部给予 17β-雌二醇或雌三醇可显著降低 ATP 诱导的自发性后足回缩持续时间（PWD），这一作用被雌激素受体拮抗剂 ICI 182,780 阻断。然而，在正常或 OVX 大鼠中，全身给予雌三醇缺乏这种类似作用。在培养的背根神经节神经元中，雌三醇减弱了α，β-亚甲基 ATP 诱导的瞬时电流，这一作用被 ICI 182,780 阻断。在完全弗氏佐剂处理（CFA）大鼠中，全身给予 17β-雌二醇或雌三醇可显著降低机械性痛觉阈值，但不改变炎症过程。在 OVX 大鼠中，雌三醇替代治疗也观察到类似作用。17β-雌二醇而非雌三醇给药可显著增加腰骶脊髓背角（SCDH）中 c-fos 的表达，但 OVX 大鼠的雌三醇替代治疗没有引起这种变化。这些结果表明，17β-雌二醇而非雌三醇在生理痛中发挥抗痛觉过敏作用。然而，外周 17β-雌二醇和雌三醇在 ATP 诱导的炎症痛中均发挥抗痛觉过敏作用。全身给予雌三醇和 17β-雌二醇在 CFA 诱导的慢性痛中发挥痛觉过敏作用。
