PMID- 30826524 OWN - NLM STAT- MEDLINE DCOM- 20191224 LR - 20191224 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 404 DP - 2019 Apr 15 TI - Acupoint Sensitization is Associated with Increased Excitability and Hyperpolarization-Activated Current (I(h)) in C- But Not Adelta-Type Neurons. PG - 499-509 LID - S0306-4522(19)30139-3 [pii] LID - 10.1016/j.neuroscience.2019.02.028 [doi] AB - Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (I(h)), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the I(h) current in acupoint sensitization has not been explained. In the present study, changes in excitability, I(h) density and the HCN channel of dorsal root ganglion (DRG) nociceptive neurons were examined in the later phase of knee osteoarthritis (KOA) rats. To investigate the neuronal specificity of acupoint sensitization, retrograde dyes were injected into the acupoints ST35 and GB37. The results showed that acupoint sensitization occurred in bilateral ST35 but not GB37 acupoints. The excitability and I(h) density of C- but not A(delta)-type neurons innervating ST35 acupoint increased in bilateral L5 DRG of acupoint sensitized rats than that of sham rats. No obvious changes were found in the excitability or I(h) density of C- and A(delta)-type neurons innervating the GB37 acupoint in the bilateral L5 DRG. HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization. Furthermore, ZD7288, an HCN current (I(h)) blocker, attenuated the acupoint sensitization of the ST35 acupoint. Taken together, our findings suggest that the increased excitability of C- but not A(delta)-type neurons and the upregulation of I(h)/HCN2 channels contribute to the formation of acupoint sensitization. CI - Copyright (c) 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Zhang, Ming AU - Zhang M AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China; Department of Central Laboratory, the General Hospital of Western Theater Command, the 270(th)Tianhui Road, Chengdu, 610083, Sichuan, China. FAU - Guo, Haiyun AU - Guo H AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Ma, Yongyuan AU - Ma Y AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Xu, Feifei AU - Xu F AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Bai, Fuhai AU - Bai F AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Liang, Shirui AU - Liang S AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Hu, Huimin AU - Hu H AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Wang, Qi AU - Wang Q AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Deng, Jiao AU - Deng J AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Dong, Hailong AU - Dong H AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. FAU - Xiong, Lize AU - Xiong L AD - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. Electronic address: mzkxlz@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190301 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels) SB - IM MH - *Acupuncture Points MH - Animals MH - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/*physiology MH - Male MH - Nerve Fibers, Myelinated/*physiology MH - Nerve Fibers, Unmyelinated/*physiology MH - Neurons/*physiology MH - Osteoarthritis, Knee/physiopathology/*therapy MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - C-type neuron OT - I(h) OT - acupoint sensitization OT - dorsal root ganglion OT - hyperpolarization-activated/cyclic nucleotide-gated channel EDAT- 2019/03/04 06:00 MHDA- 2019/12/25 06:00 CRDT- 2019/03/04 06:00 PHST- 2018/04/06 00:00 [received] PHST- 2019/02/19 00:00 [revised] PHST- 2019/02/20 00:00 [accepted] PHST- 2019/03/04 06:00 [pubmed] PHST- 2019/12/25 06:00 [medline] PHST- 2019/03/04 06:00 [entrez] AID - S0306-4522(19)30139-3 [pii] AID - 10.1016/j.neuroscience.2019.02.028 [doi] PST - ppublish SO - Neuroscience. 2019 Apr 15;404:499-509. doi: 10.1016/j.neuroscience.2019.02.028. Epub 2019 Mar 1.