GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NAα1 receptors in the medial prefrontal cortex.
GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NAα1 receptors in the medial prefrontal cortex.
复制标题
DOI：
10.1016/j.neuroscience.2016.08.005
复制
发表时间：
2016-10-15
期刊：
影响因子：
3.3
通讯作者：
Westlund KN
中科院分区：
文献类型：
--
作者：
Kaushal R;Taylor BK;Jamal AB;Zhang L;Ma F;Donahue R;Westlund KN
三叉神经性疼痛被描述为持续的痛苦的面部疼痛。本研究旨在探讨蓝斑核（LC）在慢性口面神经病理性疼痛（CCI-ION）模型中的作用。本研究探讨LC的关系，延髓背角接受三叉神经感觉神经支配和内侧前额叶皮质（mPFC）。LC是中枢神经系统去甲肾上腺素（NA）的主要来源，也是参与疼痛调制的主要核团。虽然LC对急性疼痛的下行抑制作用已经得到很好的证实，但也有报道LC对慢性神经性疼痛的促进作用。本研究通过眶下神经慢性压迫性损伤（CCI-ION）建立三叉神经痛大鼠模型。口面神经病理性疼痛的发展表明胡须垫机械过敏。通过选择性消除NA神经元，包括LC（A6细胞组），用神经毒素抗多巴胺-β-羟化酶皂草素（anti-DβH-saporin）或脑室内（i. c. v.）或进入三叉神经脊束核尾侧（spVc）。GABAA受体拮抗剂荷包牡丹碱，直接给药到LC（第8周）抑制超敏反应。这表明在三叉神经损伤后LC中GABAA信号传导的增加矛盾地产生慢性疼痛状态的兴奋性易化的效价转变。向mPFC中微量注射NAα1受体拮抗剂苯恶硫胺可减弱胡须垫超敏反应，而NAα2受体拮抗剂伊达克生则无效。因此，CCI-ION期间GABA A介导的NA神经元激活可通过mPFC中的NAα1受体促进超敏反应。这些数据表明LC是一种慢性疼痛发生器。由Elsevier Ltd代表IBRO出版。
Trigeminal neuropathic pain is described as constant excruciating facial pain. The study goal was to investigate the role of nucleus locus coeruleus (LC) in a model of chronic orofacial neuropathic pain (CCI-ION). The study examines LC’s relationship to both the medullary dorsal horn receiving trigeminal nerve sensory innervation and the medial prefrontal cortex (mPFC). LC is a major source of CNS noradrenaline (NA) and a primary nucleus involved in pain modulation. Although descending inhibition of acute pain by LC is well established, contribution of the LC to facilitation of chronic neuropathic pain is also reported. In the present study, a rat orofacial pain model of trigeminal neuropathy was induced by chronic constrictive injury of the infraorbital nerve (CCI-ION). Orofacial neuropathic pain was indicated by development of whisker pad mechanical hypersensitivity. Hypersensitivity was alleviated by selective elimination of NA neurons, including LC (A6 cell group), with the neurotoxin anti-dopamine-β-hydroxylase saporin (anti-DβH-saporin) microinjected either intracerebroventricularly (i.c.v.) or into trigeminal spinal nucleus caudalis (spVc). The GABAA receptor antagonist, bicuculline, administered directly into LC (week 8) inhibited hypersensitivity. This indicates a valence shift in which increased GABAA signaling ongoing in LC after trigeminal nerve injury paradoxically produces excitatory facilitation of the chronic pain state. Microinjection of NAα1 receptor antagonist, benoxathian, into mPFC attenuated whisker pad hypersensitivity, while NAα2 receptor antagonist, idazoxan, was ineffective. Thus, GABAA-mediated activation of NA neurons during CCI-ION can facilitate hypersensitivity through NAα1 receptors in the mPFC. These data indicate LC is a chronic pain generator. Published by Elsevier Ltd on behalf of IBRO.