Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone.
Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone.
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DOI：
10.1177/17448069211069255
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发表时间：
2022-01
期刊：
影响因子：
3.3
通讯作者：
Averitt DL
中科院分区：
文献类型：
--
作者：
Hornung RS;Raut NG;Cantu DJ;Lockhart LM;Averitt DL
口面部疼痛疾病主要由女性经历。黄体酮是一种主要的卵巢激素，具有神经保护作用和镇痛作用。我们最近报道，黄体酮可以减轻雌激素加剧的口面部疼痛行为，但尚不清楚黄体酮在三叉神经系统中的活性背后的解剖学基础是什么。据报道，黄体酮通过作用于细胞内黄体酮受体 (iPR)、膜黄体酮受体 (mPR) 或 sigma 1 受体 (Sig-1R) 发挥保护作用。其中，iPR 和 Sig-1R 据报道在疼痛中发挥作用。黄体酮还可以通过其代谢物别孕酮具有抗伤害作用。孕酮代谢为四氢孕酮需要两种酶，即 5α-还原酶和 3α-羟基类固醇脱氢酶 (3α-HSD)。黄体酮和四氢孕酮都会迅速减弱疼痛敏感性，这表明黄体酮在 Sig-1R 上的作用和/或转化为针对 GABAA 受体的四氢孕酮。在本研究中，我们研究了 Sig-1 Rs 是否在循环雌性大鼠三叉神经节内的伤害感受器中表达，以及黄体酮代谢为四氢孕酮所需的两种酶（5α-还原酶和 3α-羟基类固醇脱氢酶）是否也存在。将发情周期各个阶段的成年雌性大鼠快速斩首并收集三叉神经节。通过荧光免疫化学或蛋白质印迹对三叉神经节进行处理，以对 Sig-1R、5α-还原酶和 3α-羟基类固醇脱氢酶进行可视化和定量。在这里，我们报告说，Sig-1Rs 和参与黄体酮代谢的两种酶在雌性大鼠三叉神经节的各种伤害性感觉神经元群体中高度表达，在动情周期的四个阶段中表达水平相似。这些数据表明，三叉神经感觉神经元是黄体酮通过 Sig-1R 和/或转化为四氢孕酮的抗伤害活性的解剖学底物。
Orofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone’s activity in the trigeminal system. Progesterone has been reported to exert protective effects through actions at intracellular progesterone receptors (iPR), membrane-progesterone receptors (mPR), or sigma 1 receptors (Sig-1R). Of these, the iPR and Sig-1R have been reported to have a role in pain. Progesterone can also have antinociceptive effects through its metabolite, allopregnanolone. Two enzymes, 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD), are required for the metabolism of progesterone to allopregnanolone. Both progesterone and allopregnanolone rapidly attenuate pain sensitivity, implicating action of either progesterone at Sig-1R and/or conversion to allopregnanolone which targets GABAA receptors. In the present study, we investigated whether Sig-1 Rs are expressed in nociceptors within the trigeminal ganglia of cycling female rats and whether the two enzymes required for progesterone metabolism to allopregnanolone, 5α-reductase and 3α-hydroxysteroid dehydrogenase, are also present. Adult female rats from each stage of the estrous cycle were rapidly decapitated and the trigeminal ganglia collected. Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.
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