Involvement of A5/A7 noradrenergic neurons and B2 serotonergic neurons in nociceptive processing: a fiber photometry study.

Involvement of A5/A7 noradrenergic neurons and B2 serotonergic neurons in nociceptive processing: a fiber photometry study.
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DOI:
10.4103/1673-5374.322465
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发表时间:
2022-04
影响因子:
6.1
通讯作者:
Kuwaki T
Kuwaki T
中科院分区:
医学2区
文献类型:
--
作者:
Moriya S;Yamashita A;Masukawa D;Sakaguchi J;Ikoma Y;Sameshima Y;Kambe Y;Yamanaka A;Kuwaki T

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在中枢神经系统中,A6去甲肾上腺素(NA)和B3 5-羟色胺(5-HT)细胞群是下行抗伤害感受系统中公认的参与者,而其他NA/5-HT细胞群的特征不是很好。A5/A7NA和B2型5-羟色胺细胞投射到脊髓角,形成下行通路。我们在清醒小鼠的A5/A7 NA和B2 5-HT细胞组中记录了G-CaMP6绿色荧光信号强度,以响应急性尾部挤压刺激、急性热刺激,并在非伤害性对照测试的背景下,使用钙成像系统的纤维光度法。我们首先将G-CaMP6引入A5/A7NA或B2型5-羟色胺神经元胞体,使用在多巴胺β羟基酶或色氨酸羟基酶-2启动子的控制下携带四环素控制的反式激活剂转基因的转基因小鼠,并通过位置特异性注射腺相关病毒(AAV-Teto(3G)-G-CaMP6)。在确认了G-CaMP6的特定表达模式后,我们记录了清醒小鼠这些部位对急性伤害性刺激的G-CaMP6绿色荧光信号。A5、A7和B2细胞组的G-CaMP6荧光强度在急性伤害性刺激后迅速增加,不久后恢复到基线荧光强度。在无毒对照试验中没有观察到这一点。结果表明,急性伤害性刺激可迅速增强A5/A7NA或B2型5-羟色胺神经元的活动,而非伤害性刺激则不能。本研究提示A5/A7NA或B2型5-羟色胺神经元在中枢神经系统的伤害性信息处理中起重要作用。我们认为A5/A7/B2神经元可能是新的治疗靶点。所有进行的手术于2018年2月22日获得鹿儿岛大学机构动物使用委员会(MD17105)的批准。
In the central nervous system, the A6 noradrenaline (NA) and the B3 serotonin (5-HT) cell groups are well-recognized players in the descending antinociceptive system, while other NA/5-HT cell groups are not well characterized. A5/A7 NA and B2 5-HT cells project to the spinal horn and form descending pathways. We recorded G-CaMP6 green fluorescence signal intensities in the A5/A7 NA and the B2 5-HT cell groups of awake mice in response to acute tail pinch stimuli, acute heat stimuli, and in the context of a non-noxious control test, using fiber photometry with a calcium imaging system. We first introduced G-CaMP6 in the A5/A7 NA or B2 5-HT neuronal soma, using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamine β-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus (AAV-TetO(3G)-G-CaMP6). After confirming the specific expression patterns of G-CaMP6, we recorded G-CaMP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli. G-CaMP6 fluorescence intensity in the A5, A7, and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after, it returned to baseline fluorescence intensity. This was not observed in the non-noxious control test. The results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B2 5-HT neurons but the non-noxious stimuli do not. The present study suggests that A5/A7 NA or B2 5-HT neurons play important roles in nociceptive processing in the central nervous system. We suggest that A5/A7/B2 neurons may be new therapeutic targets. All performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University (MD17105) on February 22, 2018.
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