Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus.

Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus.
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DOI:
10.1155/2015/275126
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发表时间:
2015
影响因子:
4.6
通讯作者:
Park CK
Park CK
中科院分区:
医学3区
文献类型:
--
作者:
Park CK

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在三叉神经系统中,急性分辨率处理的中断可能导致与颞下颌关节(TMJ)相关的无法控制的炎症和慢性疼痛。目前,尚无有效的治疗颞下颌关节疼痛的方法。最近,人们认识到maresin 1是一种新发现的巨噬细胞来源的炎症消退介质,在小鼠体内是一种有效的体炎性疼痛镇痛药,没有明显的副作用,并且是体细胞系统中一种有效的内源性瞬时受体电位香草样蛋白1 (TRPV1)抑制剂。然而,在三叉神经系统中,maresin 1对TMJ疼痛的镇痛作用的分子机制尚不清楚。本研究通过TMJ注射逆行标记示踪剂DiI(一种荧光染料),研究人员发现maaresin 1可以通过g α I偶联g蛋白偶联受体抑制辣椒素诱导的TRPV1电流和DiI标记的三叉神经痛觉神经元的神经元活性。此外,马氏蛋白1阻断了TRPV1激动剂引起的自发兴奋性突触后电流频率的增加,并消除了三叉神经核TMJ炎症诱导的突触可塑性。这些结果证明了marsin 1在三叉神经系统中调控TRPV1的有效作用。因此,马皂苷1可能作为一种新的内源性抑制剂用于治疗口腔面部区域的tmj炎性疼痛。
In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ). Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1) in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye), I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.