Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice.
Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice.
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DOI：
10.1186/1744-8069-3-31
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发表时间：
2007-10-29
期刊：
影响因子：
3.3
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Chen X;Alessandri-Haber N;Levine JD
炎症介质可以直接使初级传入伤害感受器对机械和渗透刺激敏感。致敏的伤害感受器激活阈值降低，自发活动增加，分别导致痛觉过敏和疼痛症状。瞬时受体电位香草素4 （TRPV4）配体门控离子通道与炎症状态相关的机械和渗透刺激的痛觉过敏有关。为了研究TRPV4是否直接参与了炎症介质对c纤维伤害感受器的致敏机制，我们比较了TRPV4+/+和TRPV4-/-小鼠体内注射简化炎症汤（前列腺素E2和5 -羟色胺）对c纤维机械感受区的影响。注射汤后，与TRPV4-/-小鼠相比，TRPV4+/+小鼠的c -纤维对低渗刺激的反应百分比和反应幅度明显更大。此外，对于简化的炎症汤，只有TRPV4+/+小鼠的c -纤维表现出自发活性增加和机械阈值降低。TRPV4-/-小鼠c -纤维反应的这些显著损伤表明TRPV4在伤害感受器致敏中的重要性；我们认为，TRPV4作为TRPV1，是多种炎症介质对初级传入神经的伤害性作用的基础。
Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of hyperalgesia and pain, respectively. The transient receptor potential vanilloid 4 (TRPV4) ligand-gated ion channel has been implicated in the hyperalgesia for mechanical and osmotic stimuli associated with inflammatory states. To investigate whether TRPV4 directly contributes to the mechanisms of inflammatory mediator sensitization of C-fiber nociceptors, we compared the effect of the injection of simplified inflammatory soup (prostaglandin E2 and serotonin) into the mechanical receptive fields of C-fibers in TRPV4+/+ and TRPV4-/- mice in vivo. Following the injection of the soup, the percentage of C-fibers responding to a hypotonic stimulus and the magnitude of the response was significantly greater in TRPV4+/+ mice compared to TRPV4-/- mice. Moreover, in response to simplified inflammatory soup only C-fibers from TRPV4+/+ mice exhibited increased spontaneous activity and decreased mechanical threshold. These marked impairments in the response of C-fibers in TRPV4-/- mice demonstrate the importance of TRPV4 in nociceptor sensitization; we suggest that TRPV4, as TRPV1, underlies the nociceptive effects of multiple inflammatory mediators on primary afferent.
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影响因子：
4.8
作者：
Suzuki, M;Mizuno, A;Imai, M
通讯作者：
Imai, M
DOI：
10.1073/pnas.1735416100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Liedtke, W;Friedman, JM
通讯作者：
Friedman, JM
影响因子：
5.3
作者：
Alessandri-Haber, N;Dina, OA;Levine, JD
通讯作者：
Levine, JD
影响因子：
7.4
作者：
Flake, NM;Lancaster, E;Gold, MS
通讯作者：
Gold, MS
DOI：
10.1083/jcb.200409070
发表时间：
2005-03-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Andrade YN;Fernandes J;Vázquez E;Fernández-Fernández JM;Arniges M;Sánchez TM;Villalón M;Valverde MA
通讯作者：
Valverde MA