Alkali Burn Induced Corneal Spontaneous Pain and Activated Neuropathic Pain Matrix in the Central Nervous System in Mice
Alkali Burn Induced Corneal Spontaneous Pain and Activated Neuropathic Pain Matrix in the Central Nervous System in Mice
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DOI：
10.1097/ico.0000000000001336
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发表时间：
2017-11
期刊：
影响因子：
2.8
通讯作者：
Y. Xiang;Wenchang Zhou;Ping Wang;Hui Yang;F. Gao;Hongbing Xiang;A. Manyande;Yu‐ke Tian;X. Tian
中科院分区：
文献类型：
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作者：
Y. Xiang;Wenchang Zhou;Ping Wang;Hui Yang;F. Gao;Hongbing Xiang;A. Manyande;Yu‐ke Tian;X. Tian
目的：探讨碱烧伤是否引起小鼠角膜神经性疼痛并激活中枢神经系统神经性疼痛基质。方法：建立小鼠角膜碱烧伤模型（II级）。用Von Frey毛测定烧灼区机械阈值。用条件位置偏好研究自发性疼痛行为。我们在神经性疼痛基质的几个代表性区域（脊髓三叉核的2个区域（内插亚核/尾侧，Vi/Vc；尾侧亚核/上颈髓，Vc/C1）、岛叶皮质、前扣带皮质（ACC）和前腹侧髓质（RVM））研究了慢性疼痛处理中神经元激活的标志——磷酸化细胞外信号调节激酶（ERK）。此外，在另一项单独的研究中进行了药理学阻断碱烧伤小鼠ACC中的pERK激活。结果：角膜碱烧伤对角膜基底下神经纤维造成持久损伤，小鼠表现自发性疼痛行为。通过在高级神经系统神经性疼痛基质的几个代表性区域的测试，荧光ERK在Vc/C1中显着激活，而在Vi/Vc中未被激活。此外，ERK在岛叶皮质、ACC和RVM中被激活。此外，药物阻断ACC中ERK的激活可消除碱烧伤引起的角膜自发性疼痛。结论：碱烧伤可引起角膜自发性疼痛，激活中枢神经系统的神经性疼痛基质。此外，碱烧伤引起的自发性角膜疼痛需要ACC中ERK的激活。
Purpose: To explore whether alkali burn causes corneal neuropathic pain and activates the neuropathic pain matrix in the central nervous system in mice. Methods: A corneal alkali burn mouse model (grade II) was used. The mechanical threshold in the cauterized area was tested using Von Frey hairs. Spontaneous pain behavior was investigated with conditioned place preference. Phosphor extracellular signal–regulated kinase (ERK), which is a marker for neuronal activation in chronic pain processing, was investigated in several representative areas of the neuropathic pain matrix: the 2 regions of the spinal trigeminal nucleus (subnucleus interpolaris/caudalis, Vi/Vc; subnucleus caudalis/upper cervical cord, Vc/C1), insular cortex, anterior cingulated cortex (ACC), and the rostroventral medulla (RVM). Furthermore, pharmacologically blocking pERK activation in the ACC of alkali burn mice was performed in a separate study. Results: Corneal alkali burn caused long-lasting damage to the corneal subbasal nerve fibers, and mice exhibited spontaneous pain behavior. By testing in several representative areas of the neuropathic pain matrix in the higher nervous system, phosphor ERK was significantly activated in Vc/C1, but not in Vi/Vc. Also, ERK was activated in the insular cortex, ACC, and RVM. Furthermore, pharmacologically blocking ERK activation in the ACC abolished alkali burn induced corneal spontaneous pain. Conclusions: Alkali burn could cause corneal spontaneous pain and activate the neuropathic pain matrix in the central nervous system. Furthermore, activation of ERK in the ACC is required for alkali burn induced corneal spontaneous pain.