Estrogen modulation of the pronociceptive effects of serotonin on female rat trigeminal sensory neurons is timing dependent and dosage dependent and requires estrogen receptor alpha.
Estrogen modulation of the pronociceptive effects of serotonin on female rat trigeminal sensory neurons is timing dependent and dosage dependent and requires estrogen receptor alpha.
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DOI：
10.1097/j.pain.0000000000002604
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发表时间：
2022-08-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
--
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主要的雌激素雌二醇(E2)在口腔面部疼痛中的作用仍然存在争议，有研究报道E2既有促伤害作用，也有抗伤害作用。外周5-羟色胺能活动的E2调节可能是女性口腔面部疼痛疾病流行的一个机制。我们最近报道，与发情间期和雄性相比，发情前期和发情期的雌性大鼠表现出更强的5-羟色胺(5-HT)诱发的口面部表情行为。在表达瞬时受体电位香草酸1离子通道(TRPV1)的三叉神经伤害性感觉神经元中，5HT2A受体mRNA的进一步共表达有助于痛敏。E_2可能通过对5-羟色胺敏感的三叉神经伤害性感受器加重口腔面部疼痛，但低或高E_2对口腔面部疼痛的作用及其机制尚不清楚。我们假设稳态暴露于发情前期水平的E2会加剧雌性大鼠5HT诱发的口腔面部表情行为，我们探索了雌鼠的转录组，并确定了哪种E2受体参与了雌性三叉神经感觉神经元的敏化。我们报道，发情间期水平的E2对5HT诱发的口面部疼痛行为具有保护作用，这种行为随着E2浓度的增加而增加，并且E2差异地改变了三叉神经节中的几个疼痛基因。此外，E2受体与5HT2a和TRPV1在三叉神经节共表达，并通过ERα增强辣椒素诱导的信号转导。总体而言，我们的数据表明，低水平(但不高)的生理水平的E2可以保护口腔面部疼痛，我们提供的证据表明，ERα受体的激活，而不是其他因素，有助于三叉神经感觉神经元伤害性信号的敏化。
The role of the major estrogen estradiol (E2) on orofacial pain conditions remains controversial with studies reporting both a pronociceptive and antinociceptive role of E2. E2 modulation of peripheral serotonergic activity may be one mechanism underlying the female prevalence of orofacial pain disorders. We recently reported that female rats in proestrus and estrus exhibit greater serotonin (5HT)-evoked orofacial nocifensive behaviors compared to diestrus and males. Further coexpression of 5HT2A receptor mRNA in nociceptive trigeminal sensory neurons that express transient receptor potential vanilloid 1 ion channels (TRPV1) contribute to pain sensitization. E2 may exacerbate orofacial pain via 5HT-sensitive trigeminal nociceptors, but whether low or high E2 contributes to orofacial pain and by what mechanism remains unclear. We hypothesized that steady-state exposure to a proestrus level of E2 exacerbates 5HT-evoked orofacial nocifensive behaviors in female rats, we explored the transcriptome of E2-treated females, and we determined which E2 receptor contributes to sensitization of female trigeminal sensory neurons. We report that a diestrus level of E2 is protective against 5HT-evoked orofacial pain behaviors, which increase with increasing E2 concentrations, and E2 differentially alters several pain genes in the trigeminal ganglia. Further, E2 receptors co-expressed with 5HT2A and TRPV1 and enhanced capsaicin-evoked signaling in the trigeminal ganglia via ERα. Overall our data indicate that low, but not high, physiological levels of E2 protect against orofacial pain, and we provide evidence that ERα receptor activation, but not others, contribute to sensitization of nociceptive signaling in trigeminal sensory neurons.
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影响因子：
4.9
作者：
Carlsen S;Nandakumar KS;Holmdahl R
通讯作者：
Holmdahl R
影响因子：
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作者：
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通讯作者：
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影响因子：
3.5
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通讯作者：
Im HJ