PMID- 31917345 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 429 DP - 2020 Mar 1 TI - Enkephalinergic Circuit Involved in Nociceptive Modulation in the Spinal Dorsal Horn. PG - 78-91 LID - S0306-4522(19)30868-1 [pii] LID - 10.1016/j.neuroscience.2019.12.020 [doi] AB - Enkephalin (ENK) has been implicated in pain modulation within the spinal dorsal horn (SDH). Revealing the mechanisms underlying ENK analgesia entails the anatomical and functional knowledge of spinal ENK-ergic circuits. Herein, we combined morphological and electrophysiological studies to unravel local ENK-ergic circuitry within the SDH. First, the distribution pattern of spinal ENK-ergic neurons was observed in adult preproenkephalin (PPE)-GFP knock-in mice. Next, the retrograde tracer tetramethylrhodamine (TMR) or horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) in PPE-GFP mice. Immunofluorescent staining showed I-isolectin B4 (IB4) labeled non-peptidergic afferents were in close apposition to TMR-labeled PBN-projecting neurons within lamina I as well as PPE-immunoreactivity (-ir) neurons within lamina II. Some TMR-labeled neurons were simultaneously in close association with both IB4 and PPE-ir terminals. Synaptic connections of these components were further confirmed by electron microscopy. Finally, TMR was injected into the PBN in adult C57BL/6 mice. Whole-cell patch recordings showed that delta-opioid receptor (DOR) agonist, [D-Pen(2,5)]-enkephalin (DPDPE, 1 microM), significantly reduced the frequency of miniature excitatory postsynaptic current (mEPSC) and decreased the activity of TMR-labeled neurons. In conclusion, spinal ENKergic neurons receive direct excitatory inputs from primary afferents, which might be directly recruited to release ENK under the condition of noxious stimuli; ENK could inhibit the glutamatergic transmission towards projecting neurons via presynaptic and postsynaptic DORs. These morphological and functional evidence may explain the mechanisms underlying the analgesic effects exerted by ENK within the SDH. CI - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Bai, Yang AU - Bai Y AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Li, Meng-Ying AU - Li MY AD - Department of Endocrinology and Metabolism, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. FAU - Ma, Jiang-Bo AU - Ma JB AD - Department of Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, China. FAU - Li, Jia-Ni AU - Li JN AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Teng, Xiao-Yu AU - Teng XY AD - Department of Anatomy, Guangxi Medical University, Nanning, China. FAU - Chen, Ying-Biao AU - Chen YB AD - Department of Anatomy, Fujian Health College, Fuzhou, China. FAU - Yin, Jun-Bin AU - Yin JB AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Huang, Jing AU - Huang J AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Chen, Jing AU - Chen J AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Zhang, Ting AU - Zhang T AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Qiu, Xin-Tong AU - Qiu XT AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Chen, Tao AU - Chen T AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Li, Hui AU - Li H AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. FAU - Wu, Sheng-Xi AU - Wu SX AD - Department of Neurobiology, The Fourth Military Medical University, Xi'an, China. FAU - Peng, Ya-Nan AU - Peng YN AD - Joint Laboratory of Neuroscience at Hainan Medical University and The Fourth Military Medical University, Hainan Medical University, Haikou, China. FAU - Li, Xiang AU - Li X AD - Department of Orthopaedics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China. Electronic address: lixiangjsph@163.com. FAU - Kou, Zhen-Zhen AU - Kou ZZ AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China. Electronic address: plutoming@fmmu.edu.cn. FAU - Li, Yun-Qing AU - Li YQ AD - Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China; Joint Laboratory of Neuroscience at Hainan Medical University and The Fourth Military Medical University, Hainan Medical University, Haikou, China. Electronic address: deptanat@fmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200107 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 SB - IM MH - Animals MH - *Axons MH - Mice MH - Mice, Inbred C57BL MH - Neurons MH - *Nociception MH - Posterior Horn Cells MH - Spinal Cord Dorsal Horn OTO - NOTNLM OT - enkephalin OT - pain OT - preproenkephalin-GFP transgenic mouse OT - spinal dorsal horn OT - synaptic transmission EDAT- 2020/01/10 06:00 MHDA- 2021/05/15 06:00 CRDT- 2020/01/10 06:00 PHST- 2019/09/05 00:00 [received] PHST- 2019/12/10 00:00 [revised] PHST- 2019/12/11 00:00 [accepted] PHST- 2020/01/10 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/01/10 06:00 [entrez] AID - S0306-4522(19)30868-1 [pii] AID - 10.1016/j.neuroscience.2019.12.020 [doi] PST - ppublish SO - Neuroscience. 2020 Mar 1;429:78-91. doi: 10.1016/j.neuroscience.2019.12.020. Epub 2020 Jan 7.