Estradiol replacement in ovariectomized rats is antihyperalgesic in the formalin test
Estradiol replacement in ovariectomized rats is antihyperalgesic in the formalin test
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DOI：
10.1016/j.jpain.2006.10.002
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发表时间：
2007-04-01
期刊：
影响因子：
4
通讯作者：
Inturrisi, Charles E.
中科院分区：
文献类型：
--
作者：
Mannino, Christy A.;South, Samantha M.;Inturrisi, Charles E.
皮下植入17 -雌二醇或孕酮可在植入后7至24天内提供稳定的血清激素水平，并可评估这些激素替代对卵巢切除（OVX）大鼠1期和2期正式诱导行为的影响。17 β -雌二醇的分级剂量（5% - 40%）在第二阶段使福尔马林诱导的行为减少35% - 49%，而在第一阶段则没有。用自动福尔马林仪器测量。20%的β -雌二醇反应最大。20% - 17 -雌二醇的抗痛觉作用在植入后8天显著，并持续到21天。相比之下，分级剂量的黄体酮对福尔马林的任何阶段都没有影响。雌激素受体拮抗剂他莫昔芬完全阻止20% - 17 β -雌二醇植入物的抗痛觉作用。与OVX对照大鼠相比，给予20% - 17雌二醇的发情前期雌性和OVX大鼠福尔马林诱导的第2期行为明显减少。此外，与处于发情前期的雌性和给予20% -雌二醇的OVX大鼠相比，福尔马林诱导的OVX对照大鼠血清皮质酮的升高有所减弱。这些结果表明，在OVX大鼠中，雌激素替代可以恢复皮质酮对强直性疼痛的最大反应，并通过雌激素受体介导的过程抑制强直性疼痛。分别：激素替代（HR）疗法仍然是一种广泛使用的方式。我们使用了基于药代动力学的大鼠HR模型，该模型导致17 β -雌二醇的持续生理水平，以证明雌激素替代在炎症性疼痛模型（福尔马林）中的镇痛（抗痛感）作用。这些结果提示了HR治疗的一个潜在的重要结果。(C) 2007年由美国疼痛学会出版。
A subcutaneous implant of 17 beta-estradiol or progesterone provides steady-state serum hormone levels from 7 to 24 days after implantation and allows the evaluation of the effects of the replacement with these hormones on phase 1 and phase 2 formal in-induced behaviors in ovariectomized (OVX) rats. Graded doses of 17 beta-estradiol (5% to 40%) reduce formalin-induced behavior by 35% to 49% during phase 2 but not during phase 1, as; measured with an automated formalin apparatus. The maximal response is seen with 20% 17 beta-estradiol. The antihyperalgesic effect of 20% 17 beta-estradiol is significant at 8 days after implantation and persists at 21 days. In contrast, graded doses of progesterone have no effect on either phase of formalin. The estrogen receptor antagonist tamoxifen completely prevents the antihyperalgesic effect of the 20% 17 beta-estradiol implant. Formalin-induced behaviors during phase 2 are significantly less in proestrus females and OVX rats given 20% 17 beta-estradiol compared with OVX control rats. Also, the formalin-induced increase in serum corticosterone is attenuated in OVX control rats compared with proestrus females and OVX rats given 20% 17 beta-estradiol. These results indicate that estrogen replacement in OVX rats restores the maximal corticosterone response to tonic pain and, by an estrogen receptor-mediated process, inhibits tonic pain.Pe rspective: Hormone replacement (HR) therapy remains a widely used modality. We used a pharmacokinetically based rat HR model that results in continuous physiological levels of 17 beta-estradiol to demonstrate the analgesic (antihyperalgesic) effects of estrogen replacement in an inflammatory pain model (formalin). These results suggest a potentially important consequence of HR therapy. (C) 2007 by the American Pain Society.