Elevated levels of calcitonin gene-related peptide in upper spinal cord promotes sensitization of primary trigeminal nociceptive neurons.
Elevated levels of calcitonin gene-related peptide in upper spinal cord promotes sensitization of primary trigeminal nociceptive neurons.
复制标题
DOI：
10.1016/j.neuroscience.2016.10.013
复制
发表时间：
2016-12-17
期刊：
影响因子：
3.3
通讯作者：
Durham PL
中科院分区：
文献类型：
--
作者：
Cornelison LE;Hawkins JL;Durham PL
口面部疼痛包括颞下颌关节紊乱和偏头痛，其特征是三叉神经伤害性感觉神经元的外周和中枢敏感化。尽管降钙素基因相关肽(CGRP)参与了中枢敏感化的发展，但脊髓CGRP水平升高促进三叉神经初级伤害性神经元外周敏化的途径尚不清楚。本研究的目的是探讨降钙素基因相关肽在促进三叉神经节伤害性神经元敏化的三叉神经系统内双向信号传递中的作用。成年雄性SD大鼠上段脊髓注射CGRP或联合注射受体拮抗剂CGRP8-37或蛋白激酶A(PKA)抑制剂KT 5720。用von Frey纤维研究机械刺激三叉神经引起的轻度头部退缩反应。免疫组织化学方法检测脊髓PKA、GFAP、Iba1和三叉神经节P-ERK的表达。部分动物脑池内注射CGRP和固蓝染料，荧光显微镜下观察三叉神经节的变化。与对照组相比，脑池内CGRP增加了对机械刺激的致痛反应。CGRP8-37或KT 5720与CGRP联合注射可抑制突触反应。CGRP刺激脊髓表达PKA和GFAP，刺激三叉神经节神经元表达P-ERK。注射后7d，三叉神经节神经元和卫星神经胶质细胞内可见快蓝染色。我们的结果表明，上脊髓CGRP水平的升高通过激活三叉神经节神经元中的PKA和P-ERK来促进初级三叉神经痛感受神经元的敏化。我们的发现提供了三叉神经系统内双向信号传递的证据，这可以促进与外周敏化相关的三叉神经节内神经元-神经胶质细胞的通讯增加。
Orofacial pain conditions including temporomandibular joint disorder and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons. Adult male Sprague Dawley rats were injected in the upper spinal cord with CGRP or co-injected with the receptor antagonist CGRP8-37 or KT 5720, an inhibitor of protein kinase A (PKA). Nocifensive head withdrawal response to mechanical stimulation of trigeminal nerves was investigated using von Frey filaments. Expression of PKA, GFAP, and Iba1 in the spinal cord and P-ERK in the trigeminal ganglion was studied using immunohistochemistry. Some animals were co-injected intracisternally with CGRP and Fast Blue dye and trigeminal ganglion imaged using fluorescent microscopy. Intracisternal CGRP increased nocifensive responses to mechanical stimulation when compared to control levels. Co-injection of CGRP8-37 or KT 5720 with CGRP inhibited the nocifensive response. CGRP stimulated expression of PKA and GFAP in the spinal cord, and P-ERK in trigeminal ganglion neurons. Seven days post injection, Fast Blue was observed in trigeminal ganglion neurons and satellite glial cells. Our results demonstrate that elevated levels of CGRP in the upper spinal cord promote sensitization of primary trigeminal nociceptive neurons via a mechanism that involves activation of PKA centrally and P-ERK in trigeminal ganglion neurons. Our findings provide evidence of bidirectional signaling within the trigeminal system that can facilitate increased neuron-glia communication within the trigeminal ganglion associated with peripheral sensitization.
登录
查看更多内容
DOI：
10.3988/jcn.2012.8.2.89
发表时间：
2012-06
期刊：
Journal of clinical neurology (Seoul, Korea)
影响因子：
--
作者：
Bernstein C;Burstein R
通讯作者：
Burstein R
影响因子：
5
作者：
Dodick, David;Silberstein, Stephen
通讯作者：
Silberstein, Stephen
影响因子：
5.3
作者：
Han, JS;Li, WD;Neugebauer, V
通讯作者：
Neugebauer, V
DOI：
10.1177/1073858409360822
发表时间：
2010-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Gosselin RD;Suter MR;Ji RR;Decosterd I
通讯作者：
Decosterd I
影响因子：
7.4
作者：
Hansen, Rikke R.;Vacca, Valentina;Malcangio, Marzia
通讯作者：
Malcangio, Marzia