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

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Neural Regeneration Research 2022年第4期17卷 881-886页

作者： Shunpei Moriya Akira Yamashita Daiki Masukawa Junichi Sakaguchi Yoko Ikoma Yoshimune Sameshima Yuki Kambe Akihiro Yamanaka Tomoyuki Kuwaki Department of Physiology Kagoshima University Graduate School of Medical and Dental ScienceKagoshimaJapan Department of Molecular Pharmacologyand Neurobiology Yokohama City University Graduate School of MedicineYokohamaJapan Department of Pharmacology Kagoshima University Graduate School of Medical and Dental ScienceKagoshimaJapan Research Institute of Environmental Medicine Nagoya UniversityNagoyaJapan

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 B25-HT cells project to the spinal horn and form descending pathways.We recorded G-Ca MP6 green fluorescence signal intensities in the A5/A7 NA and the B25-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-Ca MP6 in the A5/A7 NA or B25-HT neuronal soma,using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamineβ-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus(AAV-Tet O(3 G)-G-Ca MP6).After confirming the specific expression patterns of G-Ca MP6,we recorded G-Ca MP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli.G-Ca MP6 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 B25-HT neurons but the non-noxious stimuli do not.The present study suggests that A5/A7 NA or B25-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.

关键词： A5 NA neurons A7 NA neurons B25-HT neurons DBH-tTA mice fiber photometry G-CaMP6 mCherry monoaminergic signaling nociception TPH-t TA mice

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