PDF(Pubmed)
Abstract：
UNASSIGNED: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster \"shingles\" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain.
UNASSIGNED: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm.
UNASSIGNED: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons.
UNASSIGNED: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.
UNASSIGNED: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm.
UNASSIGNED: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons.
UNASSIGNED: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.
摘要：
■人类带状疱疹是水痘带状疱疹病毒（VZV）感染的结果。向大鼠注射水痘带状疱疹病毒会产生类似于人类带状疱疹“带状疱疹”疼痛的疼痛。.在之前的研究中,通过向雄性大鼠的晶须垫注射VZV引起口面疼痛，并且在减弱杏仁核中央的Neurexin3（Nrxn3）表达后，疼痛反应增加。神经元从中央杏仁核下降到外侧臂旁核，口面疼痛信号上升到外侧臂旁核。中央杏仁核内的GABA能神经元通过抑制臂旁核内的活性来调节疼痛。减轻杏仁核中央Nrxn3的表达会增加臂旁核外侧的GABA释放，这表明Nrxn3通过调节GABA释放来控制疼痛。Nrxn3还可以控制神经元之间的突触连接，我们假设杏仁核中央的Nrxn3敲低会减少臂旁核外侧的GABA能突触连接的数量，并增加VZV相关的疼痛。
■为了测试这个想法，在输注表达突触素的病毒后,对杏仁核中央的GABA能细胞与臂旁核外侧的兴奋性或强啡肽阳性神经元之间的突触连接数量进行了定量.突触素是一种标记神经元突触连接的突触小泡蛋白。在杏仁核中央内注射和不注射晶须垫VZV和敲低Nrxn3的大鼠中测量了这些连接。使用避免位置逃避范式来测量面部疼痛。
■Nrxn3敲除后，臂旁核外侧的GABA能突触连接减少。连接数量减少的大鼠与VZV相关的口面部疼痛增加。疼痛标记前强啡肽的免疫染色表明，GABA能连接的减少主要与前强啡肽阳性神经元有关。
■结果表明Nrxn3减少了VZV相关的口面部疼痛，在某种程度上,通过增强中央杏仁核的GABA细胞和外侧臂旁核内的疼痛神经元之间的突触连接。
■为了测试这个想法，在输注表达突触素的病毒后,对杏仁核中央的GABA能细胞与臂旁核外侧的兴奋性或强啡肽阳性神经元之间的突触连接数量进行了定量.突触素是一种标记神经元突触连接的突触小泡蛋白。在杏仁核中央内注射和不注射晶须垫VZV和敲低Nrxn3的大鼠中测量了这些连接。使用避免位置逃避范式来测量面部疼痛。
■Nrxn3敲除后，臂旁核外侧的GABA能突触连接减少。连接数量减少的大鼠与VZV相关的口面部疼痛增加。疼痛标记前强啡肽的免疫染色表明，GABA能连接的减少主要与前强啡肽阳性神经元有关。
■结果表明Nrxn3减少了VZV相关的口面部疼痛，在某种程度上,通过增强中央杏仁核的GABA细胞和外侧臂旁核内的疼痛神经元之间的突触连接。
