Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
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DOI：
10.1016/j.ibror.2019.05.005
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发表时间：
2019-12-01
期刊：
影响因子：
2.6
通讯作者：
Kuwaki, Tomoyuki
中科院分区：
文献类型：
--
作者：
Moriya, Shunpei;Yamashita, Akira;Kuwaki, Tomoyuki
伤害性感受是一种重要的感知类型，对人类的日常生活有着重要的影响。存在一些与疼痛管理和调节相关的下行通路，其统称为下行抗伤害感受系统（DAS）。蓝斑（LC）内的去甲肾上腺素（NA）和延髓头端腹内侧区（RVM）内的5-羟色胺（5-HT）是DAS的组成部分。中缝背核（dorsal raphe，DR）的5-HT神经元大多数具有上行投射而非下行投射，它们投射到丘脑，调节伤害性感受。DAS和DR都被认为与疼痛情绪症状有关。在这项研究中，我们利用纤维光度系统，专门检查LC NA神经元和RVM/DR 5-HT神经元的活动，使用小鼠携带四环素控制的反式激活因子转基因（tTA）的控制下的多巴胺β-羟化酶启动子或色氨酸羟化酶-2启动子和位点特异性感染的腺相关病毒携带TetO G-CaMP 6基因。在确认目标群体中G-CaMP 6的特异性表达后，在暴露于急性伤害性刺激（包括捏和对尾部施加热（55 ℃））后，记录清醒小鼠中绿色荧光信号强度的变化。两种刺激均引起LC NA神经元和RVM/DR 5-HT神经元活动的快速和短暂（< 15 s）增加，而对照刺激不引起任何变化。本研究结果清楚地表明，急性伤害性刺激增加LC NA神经元和RVM/DR 5 HT神经元的活性，并建议一个可能的治疗疼痛的治疗靶点。
Nociception is an important type of perception that has major influence on daily human life. There are some descending pathways related to pain management and modulation, which are collectively known as the descending antinociceptive system (DAS). Noradrenalin (NA) in the locus coeruleus (LC) and serotonin (5-HT) in the rostral ventromedial medulla (RVM) are components of the DAS. Most 5-HT neurons in the dorsal raphe (DR) have ascending projections rather than descending projections, and they project to the thalamus that modulates nociception. Both the DAS and the DR are believed to be involved in pain-emotion symptoms. In this study, we utilized a fiber photometry system to specifically examine the activity of LC NA neurons and RVM/DR 5-HT neurons using mice carrying tetracycline-controlled transactivator transgene (tTA) under the control of either a dopamine beta-hydroxylase promoter or a tryptophan hydroxylase-2 promoter and site-specific infection of an adeno-associated virus carrying a TetO G-CaMP6 gene. After confirmation of specific expression of G-CaMP6 in the target populations, changes in green fluorescent signal intensity were recorded in awake mice upon exposure to acute nociceptive stimulation consisting of a pinch and application of heat (55 degrees C) to the tail. Both stimuli resulted in rapid and transient (< 15 s) increases in the activity of LC NA neurons and RVM/DR 5-HT neurons while the control stimuli did not induce any changes. The present results clearly indicate that acute nociceptive stimuli increase the activity of LC NA neurons and RVM/DR 5 H T neurons and suggest a possible therapeutic target for pain treatment.