Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons.
Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons.
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雌激素加剧了外周羟色胺对大鼠三叉神经元的伤害感作用。
DOI：
10.1016/j.ynpai.2021.100073
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Averitt DL
中科院分区：
文献类型：
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作者：
Kaur S;McDonald H;Tongkhuya S;Lopez CMC;Ananth S;Hickman TM;Averitt DL
5 HT诱发的伤害性行为是性二态的，并且依赖于动物的激素状态。阻断兴奋性5 HT 2A受体可减弱发情前期/发情期雌性动物中5 HT诱发的疼痛行为。与男性相比，骑自行车的女性的5-HT基础水平升高。雌激素增强辣椒素诱发的雌性三叉神经感觉神经元CGRP释放的多巴胺能神经调节。涉及三叉神经感觉神经元的口面疼痛疾病不成比例地影响女性，并且可以通过激素，特别是雌激素（E2）来调节。促炎介质如5-羟色胺（5-HT）可作用于表达瞬时受体电位香草酸1（TRPV 1）离子通道的感觉神经元，导致外周致敏。我们以前报道外周5 HT引起更大的疼痛行为，在雌性大鼠在发情前期和发情期，阶段时E2波动。尚不清楚这种相互作用在三叉神经系统中是否具有可比性。我们假设，E2加剧5-HT诱发的伤害性疼痛行为和疼痛信号在女性三叉神经感觉神经元。我们报告说，在动情期和动情前期，5 HT诱发的伤害反应行为显着增加，但通过阻断5 HT 2A受体可以减弱这种行为。除非同时给予辣椒素，否则相当剂量的5-HT对雄性动物无伤害性。当给予辣椒素，较低剂量的5-HT诱发三叉神经痛行为的女性在发情前期。此外，在触须垫的基础5 HT含量较高，骑自行车的女性相比，男性。在体外，E2增强了5 HT增强的三叉神经元CGRP释放，而阻断5 HT 2A受体并未显着减少这种释放。我们的数据表明，雌激素波动影响5-HT对三叉神经感觉神经元的原伤害性效应。
5HT-evoked nocifensive behaviors are sexually dimorphic and dependent on hormone status of the animal. Blocking the excitatory 5HT2A receptor attenuates 5HT-evoked pain behaviors in females during proestrus/estrus. Basal levels of 5HT are elevated in cycling females as compared to males. Estrogen potentiates serotonergic neuromodulation of capsaicin-evoked CGRP release in female trigeminal sensory neurons. Orofacial pain disorders involving trigeminal sensory neurons disproportionately affect women and can be modulated by hormones, especially estrogen (E2). Proinflammatory mediators, like serotonin (5HT), can act on sensory neurons expressing the transient receptor potential vanilloid 1 (TRPV1) ion channel, resulting in peripheral sensitization. We previously reported peripheral 5HT evokes greater pain behaviors in the hindpaw of female rats during proestrus and estrus, stages when E2 fluctuates. It is unknown if this interaction is comparable in the trigeminal system. We hypothesized that E2 exacerbates 5HT-evoked nocifensive pain behaviors and pain signaling in female trigeminal sensory neurons. We report 5HT-evoked nocifensive behaviors are significantly higher during estrus and proestrus, which is attenuated by blocking the 5HT2A receptor. The comparable dose of 5HT was not nociceptive in males unless capsaicin was also administered. When administered with capsaicin, a lower dose of 5HT evoked trigeminal pain behaviors in females during proestrus. Further, basal 5HT content in the vibrissal pad was higher in cycling females compared to males. Ex vivo, E2 enhanced 5HT-potentiated CGRP release from trigeminal neurons, which was not significantly reduced by blocking the 5HT2A receptor. Our data indicates that estrogen fluctuation influences the pronociceptive effects of 5HT on trigeminal sensory neurons.