Estrogens Exacerbate Nociceptive Pain via Up-Regulation of TRPV1 and ANO1 in Trigeminal Primary Neurons of Female Rats.
Estrogens Exacerbate Nociceptive Pain via Up-Regulation of TRPV1 and ANO1 in Trigeminal Primary Neurons of Female Rats.
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DOI：
10.1210/en.2016-1218
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发表时间：
2016-09
期刊：
影响因子：
4.8
通讯作者：
K. Yamagata;Mitsutaka Sugimura;Miki Yoshida;S. Sekine;Akiyo Kawano;Aiko Oyamaguchi;Hiroharu Maegawa;H. Niwa
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文献类型：
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作者：
K. Yamagata;Mitsutaka Sugimura;Miki Yoshida;S. Sekine;Akiyo Kawano;Aiko Oyamaguchi;Hiroharu Maegawa;H. Niwa
一些三叉神经疼痛障碍表现出性别差异，而高水平的雌激素可能是这些差异的基础。瞬时受体电位香草素1(TRPV1)和异辛胺1(ANO1)之间的相互作用在外周伤害性感受中起重要作用。然而，TRPV1和ANO1是否参与雌激素调节的三叉神经痛敏感性尚不清楚。在本研究中，我们用选择性TRPV1激动剂辣椒素(Capsaicin，Cap)对高剂量E2(HE)或低剂量E2(LE)处理的去卵巢大鼠进行2天的眼表注射，通过行为学和免疫组织学实验研究了雌二醇(E2)对伤害性感受的调节作用。此外，我们还利用实时荧光定量聚合酶链式反应研究了雌二醇对三叉神经节内TRPV1和ANO1mRNA表达水平的影响。在行为学实验中，与LE组相比，HE组对Cap诱发的突触行为有明显的增强作用。免疫组织化学结果显示，HE组大鼠三叉神经尾侧亚核/上颈髓c-Fos免疫反应阳性细胞数明显多于LE组。两组三叉神经腹侧内侧/尾侧c-Fos免疫反应阳性细胞数相似。实时定量聚合酶链式反应显示，HE组的TRPV1和ANO1mRNA水平显著高于LE组。因此，高水平的雌激素可能是Cap诱导的伤害性疼痛的一个危险因素，TRPV1和ANO1的雌激素依赖性增加可能参与了三叉神经区伤害性反应的调节。
Several trigeminal pain disorders show sex differences, and high levels of estrogens may underlie these differences. The interaction between transient receptor potential vanilloid 1 (TRPV1) and anoctamin 1 (ANO1) plays an important role in peripheral nociception. However, whether TRPV1 and ANO1 are involved in estrogen-modulated trigeminal pain sensitivity is unclear. In this study, we examined estradiol (E2) modulation of nociception through behavioral and immunohistological experiments after application of capsaicin (Cap), a selective TRPV1 agonist, onto the ocular surface in ovariectomized rats treated with high-dose E2 (HE) or low-dose E2 (LE) for 2 days. In addition, we used real-time PCR to study the effects of E2 on the expression levels of TRPV1 and ANO1 mRNA in trigeminal ganglia. In the behavioral experiment, the HE group showed significant potentiation of Cap-evoked nocifensive behavior compared with the LE group. Immunohistochemistry showed that Cap evoked a significantly greater number of cells that were immunoreactive for c-Fos, a marker of nociceptive activation, in the trigeminal subnucleus caudalis/upper cervical cord in the HE group than in the LE group. The number of c-Fos-immunoreactive cells in the ventral trigeminal interpolaris/caudalis were similar in the 2 groups. Real-time PCR showed that the levels of TRPV1 and ANO1 mRNA in the HE group were significantly higher than levels in the LE group. Thus, high levels of estrogens may be a risk factor for Cap-evoked nociceptive pain, and estrogen-dependent increases in TRPV1 and ANO1 are likely involved in modulating the nociceptive response in the trigeminal area.