Vanilloid receptor TRPV1-mediated phosphorylation of ERK in murine adjuvant arthritis.
Vanilloid receptor TRPV1-mediated phosphorylation of ERK in murine adjuvant arthritis.
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DOI：
10.1016/j.joca.2008.06.015
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发表时间：
2009-02
影响因子：
7
通讯作者：
Valtschanoff JG
中科院分区：
文献类型：
--
作者：
Chen Y;Willcockson HH;Valtschanoff JG
由支配关节的感觉神经元表达的香草受体TRPV1与关节炎有关，但其机制尚不完全清楚。一种可能性是TRPV1激活的下游效应是由细胞外调节的激酶ERK介导的。ERK在对有害刺激的反应中被磷酸化（pERK），其抑制作用在几种疼痛模型中被发现是抗伤害性的。我们在这里想要确定TRPV1是否可能通过erk介导的途径参与关节炎的疼痛超敏反应和炎症。我们使用佐剂诱导的踝关节关节炎（AIA）模型，利用多重免疫荧光技术研究了TRPV1基因敲除（KO）小鼠与相同遗传背景的野生型小鼠相比，背根神经节（DRG）和脊髓背角感觉传入神经元中p-ERK表达的变化。在小鼠体内诱导AIA 2 - 3周后，AIA一侧DRG和脊髓中表达p-ERK的神经元数量明显高于对侧注射侧。DRG中p-ERK阳性神经元也表达TRPV1的比例增加，表明ERK的激活优先发生在TRPV1阳性神经元中。此外，与WT小鼠相比，TRPV1-KO小鼠感觉神经元中ERK的激活降低。这些p-ERK表达的变化与疼痛行为和关节组织病理学的变化相关：与WT小鼠相比，TRPV1-KO小鼠的伤害性行为和关节炎的严重程度降低。我们的结果支持这样一种观点，即初级传入神经元中ERK的激活至少部分是由TRPV1介导的。在缺乏TRPV1的情况下，AIA小鼠模型中关节痛的体征和组织病理学均有所减轻。我们得出结论，TRPV1在关节传入途径中由神经元表达，通过erk介导的途径参与关节炎的发病机制。
The vanilloid receptor TRPV1, expressed by sensory neurons that innervate joints, is implicated in arthritis but the mechanisms are not fully understood. One possibility is that downstream effects of activation of TRPV1 are mediated by the extracellularly-regulated kinase ERK. ERK is phosphorylated (pERK) in sensory neurons in response to noxious stimuli and its inhibition has been found to be antinociceptive in several pain models. We here wanted to ascertain whether TRPV1 may contribute to the pain hypersensitivity and inflammation of arthritis via an ERK-mediated pathway. We used a model of adjuvant-induced arthritis (AIA) of the ankle and investigated the changes in expression of p-ERK in sensory afferent neurons in dorsal root ganglia (DRG) and spinal dorsal horn of TRPV1 knockout (KO) mice, compared to wild type mice of the same genetic background, using multiple immunofluorescence. Two-three weeks after inducing AIA in mice, the number of neurons in DRG and spinal cord that expressed p-ERK was significantly higher on the side of AIA than on the contralateral, vehicle-injected side. The fraction of p-ERK-positive neurons in the DRG that also expressed TRPV1 was increased, indicating that activation of ERK occurred preferentially in TRPV1-positive neurons. Moreover, TRPV1-KO mice had reduced activation of ERK in sensory neurons, compared to WT mice. These changes in expression of p-ERK correlated with changes in pain behavior and joint histopathology: TRPV1-KO mice had reduced nociceptive behavior and severity of arthritis, compared to WT mice. Our results support the idea that activation of ERK in primary afferent neurons is mediated, at least in part, by TRPV1. In the absence of TRPV1, the signs of arthralgia and histopathology in the mouse model of AIA are reduced. We conclude that TRPV1, expressed by neurons in the articular afferent pathway, contributes to the pathogenesis of arthritis via an ERK-mediated pathway.
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影响因子：
2.5
作者：
Carlton, SM;Coggeshall, RE
通讯作者：
Coggeshall, RE
影响因子：
--
作者：
Helyes, Z;Szabó, A;Szolcsányi, J
通讯作者：
Szolcsányi, J
影响因子：
2.1
作者：
Cruz, F
通讯作者：
Cruz, F
影响因子：
3.4
作者：
Guo, A;Vulchanova, L;Elde, R
通讯作者：
Elde, R
DOI：
10.1016/s0169-328x(03)00284-5
发表时间：
2003-08-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Galan, A;Cervero, F;Laird, JMA
通讯作者：
Laird, JMA