Wei Xiaomei, Yan Jin, Tillu Dipti, Asiedu Marina, Weinstein Nicole, Melemedjian Ohannes, Price Theodore, Dussor Gregory
Department of Pharmacology, The University of Arizona College of Medicine, USA.
Department of Pharmacology, The University of Arizona College of Medicine, USA School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA.
Cephalalgia. 2015 Oct;35(12):1054-64. doi: 10.1177/0333102414566861. Epub 2015 Jan 19.
Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine.
NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model.
Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6).
These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine.
虽然压力导致偏头痛发生的机制尚未完全明确，但普遍认为压力会引发偏头痛。这些研究的目的是探究去甲肾上腺素（NE），即主要的交感传出递质，是否作用于脑膜中可能导致偏头痛疼痛的过程。
使用头痛行为模型将NE应用于大鼠硬脑膜。制备从硬脑膜逆行标记的大鼠三叉神经节原代培养物和大鼠硬脑膜成纤维细胞原代培养物。采用膜片钳电生理学、蛋白质免疫印迹法和酶联免疫吸附测定法来检测NE的作用。使用行为性头痛模型将经NE处理的成纤维细胞培养物的条件培养基应用于硬脑膜。
向硬脑膜注射NE以及注射来自经NE刺激的成纤维细胞的培养基，均可导致清醒大鼠面部皮肤和后爪出现痛觉过敏。将NE应用于培养的硬脑膜传入神经可增加对电流注射的动作电位发放。将NE应用于硬脑膜成纤维细胞可增加细胞外信号调节激酶（ERK）的磷酸化并导致白细胞介素-6（IL-6）的释放。
这些数据表明，NE可通过作用于硬脑膜传入神经和硬脑膜成纤维细胞，促进来自脑膜的伤害性信号传导。NE的这些作用共同可能导致偏头痛的头痛期。
