Progesterone mediates gonadal hormone differences in tactile and thermal hypersensitivity following L5 nerve root ligation in female rats
Progesterone mediates gonadal hormone differences in tactile and thermal hypersensitivity following L5 nerve root ligation in female rats
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DOI：
10.1016/j.neuroscience.2005.11.048
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
--
作者：
LaCroix-Fralish, ML;Tawfik, VL;DeLeo, JA
在临床和动物研究中，对热刺激和触觉刺激的反应大小的性别差异已经被证明。与雄性相比，雌性大鼠通常对疼痛刺激表现出更低的阈值，并且在神经损伤后表现出更强烈的反应。有大量证据表明，性激素参与了这种性别差异的调节。在这项研究中，我们试图利用慢性激素替代范式来确定哪些性腺激素参与了雌性大鼠在实验性神经根损伤之前和之后观察到的雌性超敏反应的调节。雌性大鼠去卵巢后，皮下植入含有17β-雌二醇、孕酮(P)、17β-雌二醇+孕酮或安慰剂的激素颗粒。我们的结果表明，与性腺完整的雄性大鼠相比，只有单独接受黄体酮的雌性大鼠组在卵巢切除后保持了超敏表型。这一结果是在未受伤的雌性大鼠对热刺激的反应以及在L5神经根结扎后对热刺激和触觉刺激的反应中观察到的，L5神经根结扎是一种与腰神经根病相关的下腰痛模型。死后对血清性激素浓度的分析表明，激素操作是成功的，外源性激素水平与假卵巢切除对照组的生理水平相似。综上所述，这些结果表明黄体酮在L5神经根结扎后女性触觉和温度过敏增强的调节中起关键作用。(C)2005年IBRO。爱思唯尔有限公司出版。保留所有权利。
Sex differences in the magnitude of response to thermal and tactile stimuli have been demonstrated in both clinical and animal studies. Female rats typically display lower thresholds to painful stimuli and display more robust responses following nerve injury as compared with males. There is a,body of evidence implicating the sex hormones in mediating this sex difference. In the present study, we sought to determine which gonadal hormones were involved in mediating the observed female hypersensitivity in female rats both prior to and following experimental nerve root injury using a chronic hormone replacement paradigm. Female rats were ovariectomized and hormone pellets containing 17 beta-estradiol, progesterone (P), 17 beta-estradiol+progesterone or placebo were implanted s.c. Our results demonstrate that only the group of female rats that received progesterone alone maintained the hypersensitive phenotype following ovariectomy, compared with gonadally intact male rats. This result was observed both in response to thermal stimuli in non-injured female rats and to thermal and tactile stimuli following L5 nerve root ligation, a model of low back pain associated with lumbar radiculopathy. Postmortem analysis of serum gonadal hormone concentrations demonstrates that the hormonal manipulations were successful and the exogenous hormones were similar to physiological levels observed in the sham-ovariectomized controls. Taken together, these results demonstrate the critical role for progesterone in mediating enhanced female tactile and thermal hypersensitivity following L5 nerve root ligation. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.