Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura.
Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura.
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DOI：
10.1186/1744-8069-8-66
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发表时间：
2012-09-12
期刊：
影响因子：
3.3
通讯作者：
Cao YQ
中科院分区：
文献类型：
--
作者：
Huang D;Li S;Dhaka A;Story GM;Cao YQ
偏头痛和其他头痛疾病影响了很大比例的人口，并导致衰弱性疼痛。支配硬脑膜和脑血管的三叉神经初级传入神经元的激活和敏化是“头痛回路”中的关键步骤。许多硬脑膜传入神经元对痛觉和炎性物质有反应。鉴于瞬时受体电位（TRP）通道家族在感受化学刺激和介导炎症性疼痛中的明确作用，我们研究了TRP通道在硬脑膜传入神经元中的表达。我们使用两种荧光示踪剂逆行标记成年小鼠的硬脑膜传入神经元，并分别使用降钙素基因相关肽免疫反应性（CGRP-IR）和异凝集素B4（IB 4）结合作为标记物，定量肽能和非肽能神经元群体的丰度。采用免疫组织化学方法，我们比较了TRPV 1和TRPA 1通道在硬脊膜传入神经元和整个三叉神经节（TG）神经元中的表达。为了研究TRPM 8通道的分布，我们标记了表达TRPM 8位点法尼基化增强型绿色荧光蛋白（EGFPf）的小鼠硬脑膜传入神经元。我们使用最近邻测量来预测TG中硬脑膜传入神经元和表达TRPA 1或TRPM 8通道的神经元之间的空间关联。我们报告，硬脑膜传入神经元的大小显着大于总TG神经元和面部皮肤传入。大约40%的硬脑膜传入神经元表现出IB 4结合。令人惊讶的是，含有CGRP-ir的硬脑膜传入神经元的百分比显着低于总TG神经元和面部皮肤传入。TRPV 1和TRPA 1通道都在硬脑膜传入神经元中表达。此外，最近邻测量表明TRPA 1表达神经元聚集在硬膜传入神经元的子集周围。有趣的是，TRPM 8表达神经元几乎不存在于硬脑膜传入群体中，这些神经元也不聚集在硬脑膜传入神经元周围。总之，我们的研究结果表明，TRPV 1和TRPA 1，而不是TRPM 8通道可能有助于硬膜传入神经元的兴奋和随后的激活头痛电路。这些结果为进一步了解TRP通道在头痛病理生理学中的功能意义提供了解剖学基础。
Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM8-expressing neurons are virtually absent in the dural afferent population, nor do these neurons cluster around dural afferent neurons. Taken together, our results suggest that TRPV1 and TRPA1 but not TRPM8 channels likely contribute to the excitation of dural afferent neurons and the subsequent activation of the headache circuit. These results provide an anatomical basis for understanding further the functional significance of TRP channels in headache pathophysiology.
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DOI：
10.1523/jneurosci.4686-08.2008
发表时间：
2008-12-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Han BH;Zhou ML;Abousaleh F;Brendza RP;Dietrich HH;Koenigsknecht-Talboo J;Cirrito JR;Milner E;Holtzman DM;Zipfel GJ
通讯作者：
Zipfel GJ
DOI：
10.1152/physiol.00026.2008
发表时间：
2008-12
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Bessac BF;Jordt SE
通讯作者：
Jordt SE
影响因子：
7.4
作者：
Harrington, Andrea M.;Hughes, Patrick A.;Brierley, Stuart M.
通讯作者：
Brierley, Stuart M.
影响因子：
5
作者：
Ivanusic, Jason J.;Kwok, Matthew M. K.;Jennings, Ernest A.
通讯作者：
Jennings, Ernest A.
影响因子：
16.2
作者：
Colburn, Raymond W.;Lubin, Mary Lou;Qin, Ning
通讯作者：
Qin, Ning