TLR4 deficiency abrogated widespread tactile allodynia, but not widespread thermal hyperalgesia and trigeminal neuropathic pain after partial infraorbital nerve transection
TLR4 deficiency abrogated widespread tactile allodynia, but not widespread thermal hyperalgesia and trigeminal neuropathic pain after partial infraorbital nerve transection
复制标题
TLR4缺乏消除了广泛的触觉异常性疼痛，但不能消除部分眶下神经横断后的广泛热痛觉过敏和三叉神经性疼痛
DOI：
10.1097/j.pain.0000000000001100
复制
发表时间：
2018-02-01
期刊：
影响因子：
7.4
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Hu, Ting-Ting;Wang, Ran-Ran;Chen, Zhong
摘要小鼠眶下神经部分切断后的疼痛敏感化不仅表现在口面部，而且可向远处扩散。Toll样受体4（TLR 4）在口面部疼痛及其扩散过程中的作用尚不清楚。在这里，我们发现由于Tr 4基因点突变（C3 H/HeJ）或自发缺失（C57 BL/10 ScNJ）而导致TLR 4缺陷的小鼠在p-IONX后以与它们各自的野生型（C3 HeB/FeJ或C57 BL/6 J）平行的方式在触须垫中产生触觉异常性疼痛和热痛觉过敏。然而，在后爪异常性疼痛是不存在的TLR 4缺陷的小鼠。脑池内或鞘内施用的TLR 4与LPS-RS的药理学拮抗作用消除了后爪中的异常性疼痛，而不影响触须垫中的超敏反应和后爪中的痛觉过敏。尽管TNF-α表达在髓质和腰髓中均上调，但野生型中TLR 4下游分子MyD 88的表达仅在p-IONX后在腰髓中增加。相比之下，后爪过敏性部分坐骨神经结扎后显着减弱TLR 4缺失。超敏反应，这并没有蔓延到触须垫，伴随着上调MyD 88在腰髓，而不是在髓质。这些结果表明，TLR 4参与了口面疼痛的异常性疼痛成分向远处身体部位的传播，但不参与三叉神经痛或其痛觉过敏成分的传播。这项研究表明，TLR 4可能作为一个潜在的目标管理广泛的异常性疼痛与口面疼痛。
Abstract Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. However, allodynia in the hind paw was absent in mice with TLR4 deficiency. Pharmacological antagonism of TLR4 with LPS-RS, administered either intracisternally or intrathecally, abrogated allodynia in the hind paw without affecting the hypersensitivity in the vibrissal pad and hyperalgesia in the hind paw. Although TNF-&agr; expression was upregulated in both the medulla and lumbar cord, the expression of TLR4 downstream molecule MyD88 increased only in the lumbar cord after p-IONX in wild types. By contrast, hind paw hypersensitivity after partial sciatic nerve ligation was significantly attenuated by TLR4 deletion. The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.