Sumatriptan inhibits TRPV1 channels in trigeminal neurons.
Sumatriptan inhibits TRPV1 channels in trigeminal neurons.
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DOI：
10.1111/j.1526-4610.2011.02053.x
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发表时间：
2012-05
期刊：
影响因子：
5
通讯作者：
Premkumar LS
中科院分区：
文献类型：
--
作者：
Evans MS;Cheng X;Jeffry JA;Disney KE;Premkumar LS
了解瞬时电位受体香草酸1（TRPV1）离子通道在舒马普坦缓解三叉神经痛感受器介导的疼痛中的可能作用。TRPV1通道在小的伤害感受性感觉神经元中表达。在背根神经节（DRG）中，含有TRPV1的伤害感受器介导某些类型的炎性疼痛。三叉神经伤害感受系统中的脑硬脑膜和血管的神经源性炎症被认为在偏头痛中是重要的，但是在传导偏头痛中重要的离子通道尚不清楚。舒马曲坦是一种有效治疗偏头痛和丛集性头痛的药物。我们推测舒马曲坦可能调节三叉神经伤害性系统中TRPV1通道的活性。我们使用免疫组织化学检测TRPV1通道蛋白的存在，在急性分离的三叉神经节（TG）中进行全细胞记录以检测TRPV1通道的功能，并在三叉神经核尾侧（TNC）中进行全细胞记录以检测神经递质从三叉神经元释放到二级感觉神经元的影响。通过用DiI标记硬脑膜伤害感受器来评估对投射到硬脑膜的TG神经元的特异性影响。免疫组织化学显示TRPV1通道存在于硬脑膜、三叉神经节和三叉神经核尾侧。辣椒素，TRPV1激动剂，产生去极化和重复动作电位放电的电流钳记录和大的内向电流电压钳记录从急性分离的TG神经元，表明TRPV1通道在三叉神经元的功能。辣椒素增加自发兴奋性突触后电流（sEPSC）在第二层的神经元在TNC切片，表明这些通道有中枢突触传递的生理作用。选择性抗偏头痛药物舒马曲坦（10 μM）可抑制TG中TRPV 1介导的内向电流。以及辣椒素诱导的TNC切片中的sEPSC。辣椒素和舒马曲坦在急性分离的DiI标记的支配硬脑膜的TG神经元中发现了相同的效果。我们的研究结果建立在以前的工作表明，TRPV1通道在三叉神经伤害感受器发挥作用，颅面疼痛。我们的研究结果，TRPV1是抑制特定的抗偏头痛药物舒马曲坦，TRPV1通道的功能神经元投射到脑硬脑膜表明这些通道在偏头痛或丛集性头痛的特定作用。
To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors. TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia (DRG), TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system. We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI. Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, trigeminal ganglion, and in the trigeminal nucleus caudalis. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 μM), a selective anti-migraine drug inhibited TRPV1-mediated inward currents in TG. and capsaicin-elicited sEPSCs in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI-labeled TG neurons innervating cerebral dura. Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache.
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影响因子：
7.4
作者：
Link, Andrea Stephanie;Kuris, Aniko;Edvinsson, Lars
通讯作者：
Edvinsson, Lars
DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
3.4
作者：
Guo, A;Vulchanova, L;Elde, R
通讯作者：
Elde, R
DOI：
10.1124/jpet.103.059808
发表时间：
2004-04-01
影响因子：
3.5
作者：
Akerman, S;Kaube, H;Goadsby, PJ
通讯作者：
Goadsby, PJ
影响因子：
2.5
作者：
Bae, YC;Oh, JM;Valtschanoff, JG
通讯作者：
Valtschanoff, JG