LPS Sensitizes TRPV1 via Activation of TLR4 in Trigeminal Sensory Neurons
LPS Sensitizes TRPV1 via Activation of TLR4 in Trigeminal Sensory Neurons
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DOI：
10.1177/0022034511400225
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发表时间：
2011-06-01
影响因子：
7.6
通讯作者：
Hargreaves, K. M.
中科院分区：
文献类型：
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作者：
Diogenes, A.;Ferraz, C. C. R.;Hargreaves, K. M.
最近的研究表明，脂多糖（LPS）受体（TLR4）表达在TRPV1的三叉神经感觉神经元。在这项研究中，我们评估了LPS是否激活三叉神经元，并通过TLR4敏化TRPV1反应。为了验证这一新的假设，我们首先证明了LPS与三叉神经元中的受体竞争性结合。第二，我们证明了LPS引起细胞内钙积累（Ca（2+））（i）和内向电流的浓度依赖性增加。第三，通过（Ca（2+））（i）、降钙素基因相关肽的释放和内向电流测量，LPS显著地使TRPV 1对辣椒素敏感。重要的是，选择性TLR4拮抗剂阻断了这些作用。对这些数据的分析共同表明，LPS能够直接激活三叉神经元，并通过TLR4介导的机制致敏TRPV1。这些发现与三叉神经神经元能够检测导致TRPV1致敏的病原性细菌成分的假设一致，可能有助于在细菌感染中经常观察到的炎性疼痛。
Recent studies have demonstrated that the lipopolysaccharide (LPS) receptor (TLR4) is expressed in TRPV1 containing trigeminal sensory neurons. In this study, we evaluated whether LPS activates trigeminal neurons, and sensitizes TRPV1 responses via TLR4. To test this novel hypothesis, we first demonstrated that LPS binds to receptors in trigeminal neurons using competitive binding. Second, we demonstrated that LPS evoked a concentration-dependent increase in intracellular calcium accumulation (Ca(2+))(i) and inward currents. Third, LPS significantly sensitized TRPV1 to capsaicin measured by (Ca(2+))(i), release of calcitonin gene-related peptide, and inward currents. Importantly, a selective TLR4 antagonist blocked these effects. Analysis of these data, collectively, demonstrates that LPS is capable of directly activating trigeminal neurons, and sensitizing TRPV1 via a TLR4-mediated mechanism. These findings are consistent with the hypothesis that trigeminal neurons are capable of detecting pathogenic bacterial components leading to sensitization of TRPV1, possibly contributing to the inflammatory pain often observed in bacterial infections.