Within the reticular thalamic nucleus neurons express gamma aminobutyric acid (GABA) and these cells project to the ventral posteromedial thalamic nucleus. When GABA activity decreases the activity of excitatory cells in the ventral posteromedial nucleus would be expected to increase. In this study, we addressed the hypothesis that attenuating GABAergic cells in the reticular thalamic nucleus increases excitatory activity in the ventral posteromedial nucleus increasing varicella zoster virus (VZV) associated pain in the orofacial region. Adeno-associated virus (AAV) was infused in the reticular thalamic nucleus of Gad1-Cre rats. This virus transduced a G inhibitory designer receptor exclusively activated by designer drugs (DREADD) gene that was Cre dependent. A dose of estradiol that was previously shown to reduce VZV pain and increase GABAergic activity was administered to castrated and ovariectomized rats. Previous studies suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons and decreasing the activity of excitatory cells within the lateral thalamic region. The ventral posteromedial nucleus was infused with AAV containing a GCaMP6f expression construct. A glass lens was implanted for miniscope imaging. Our results show that the activity of GABA cells within the reticular thalamic region decreased with clozapine N-oxide treatment concomitant with increased calcium activity of excitatory cells in the ventral posteromedial nucleus and an increased orofacial pain response. The results suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons within the reticular thalamus that then inhibit excitatory activity in ventral posteromedial nucleus causing a reduction in orofacial pain.

在网状丘脑核内，神经元表达 γ 氨基丁酸 (GABA)，这些细胞投射到丘脑腹侧后内侧核。当 GABA 活性降低时，腹侧后内侧核中的兴奋性细胞的活性预计会增加。在这项研究中，我们提出了一个假设，即减弱网状丘脑核中的 GABA 能细胞会增加腹侧后内侧核的兴奋活性，从而增加口面部区域水痘带状疱疹病毒 (VZV) 相关的疼痛。腺相关病毒 (AAV) 被注入 Gad1-Cre 大鼠的网状丘脑核中。这种病毒转导了一种 G 抑制性设计受体，该受体专门由 Cre 依赖的设计药物 (DREADD) 基因激活。给去势和切除卵巢的大鼠施用一剂先前显示可减轻 VZV 疼痛并增加 GABA 能活性的雌二醇。先前的研究表明，雌二醇通过增加抑制性神经元的活动和降低侧丘脑区域内兴奋性细胞的活动来减轻带状疱疹的疼痛。腹侧后内侧核注入含有 GCaMP6f 表达构建体的 AAV。植入玻璃透镜用于微型显微镜成像。我们的研究结果表明，氯氮平 N-氧化物治疗后网状丘脑区域内 GABA 细胞的活性降低，同时腹侧后内侧核中兴奋性细胞的钙活性增加，口面部疼痛反应增加。