Role of parabrachial-central amygdala system in inflammation-pain association

臂旁中央杏仁核系统在炎症-疼痛关联中的作用

• 批准号: 21H02816
• 负责人: 加藤 総夫
• 金额: $ 10.98万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21H02816/
• 关键词: 痛み; 腕傍核; 扁桃体; 炎症; 痛覚変調性疼痛; 扁桃体中心核; FosTRAPマウス; 光遺伝学; CGRP; Muオピオイド受容体; lipopolysaccharide; 中枢性感作; 広汎性痛覚過敏; 化学遺伝学

Fos発現およびエストロゲン受容体活性化依存的にcre recombinaseを発現するFosTRAP2マウスとcre recombinase依存的にtdTomotoを発現するAi14マウスを交配させたFosTRAP x tdTomato マウスの腕傍核にchannelrhodopsin-2 （ChR2）発現ベクターを導入し，炎症性一過性疼痛活性化ニューロン（痛みニューロン）にChR2を発現させた．同マウスにlipopolysaccharide (LPS) を投与して全身性炎症を誘発した．2-24 時間後，脳スライスで終末を光刺激し，腕傍核→扁桃体中心核シナプス伝達，および，それに引き続き活性化される扁桃体中心核内抑制性シナプス伝達を評価した．LPSは，用量依存的に下肢痛覚過敏を引き起こし，腕傍核，扁桃体中心核のFos発現を増加した．腕傍核痛みニューロンから扁桃体中心核痛みニューロンへのシナプス伝達において，LPS処置群ではfeedforward inhibition回路を介して2次的に生じる抑制性シナプス伝達の振幅が有意に増大した．一方，calcitonin gene-related peptide (CGRP)-cre発現マウスで，腕傍核にcre依存的ChR2発現ベクターを注入し，LPS投与後の腕傍核－扁桃体中心核間シナプス伝達を測定したところ全記録例でmuオピオイド受容体アゴニスト（DAMGO）がシナプス伝達を著明に抑制する事実を見出した．一方，同受容体インバースアゴニスト（CTAP）は，腕傍核－扁桃体中心核間シナプス伝達を増強させ，その増強率はLPS処置群で有意に大きかった．LPSによる全身炎症が内因性オピオイド系を活性化させ腕傍核から扁桃体中心核への侵害受容情報伝達を抑制する可能性が示唆された．

FosTRAP2 and cre recombinase dependent on receptor activation are developed by FosTRAP x tdTomato in the nucleus carpi adjacent to the wrist, channelrhodopsin-2 (ChR2) is developed, and inflammatory transient pain activation is developed. 2 -24 hours after LPS administration, the terminal light stimulation induced systemic inflammation, and the activation of the inhibitory system in the tonsillar nucleus increased.LPS dose-dependently induced the onset of leg pain and allergy, and the Fos in the paracarpal nucleus and the tonsillar nucleus increased. The amplitude of LPS treatment group was intentionally increased due to the second generation of the feedforward inhibition loop. On the other hand, calcitonin gene-related peptide (CGRP)-cre expression was detected, cre dependent ChR2 expression in the paracarpal nucleus was detected after LPS injection, and the expression of ChR2 in the paracarpal nucleus-tonsil central nucleus was detected after LPS injection. On the other hand, the receptor pathway (CTAP) increased in the paracarpal nucleus tonsillar nucleus, and the rate of increase was significantly higher than that of LPS treatment group. LPS treatment group showed the possibility of inhibition of endogenous receptor pathway activation in the paracarpal nucleus tonsillar nucleus.

项目成果

The structures that excite the central amygdala neurons and pain network in orofacial inflammatory pain

口面部炎性疼痛中激发中央杏仁核神经元和疼痛网络的结构

• 发表时间: 2022
• 作者: Okuda T;Uchiyama S;Sato N;Takahashi Y;Kato F.
• 通讯作者: Kato F.

いたみとはなにか？ 脳中心主義的痛みの理解を目指して

什么是伤害？

• 发表时间: 2021
• 作者: Nagano Masaaki;Kohsaka Shinji;Hayashi Takuo;Ueno Toshihide;Kojima Shinya;Shinozaki-Ushiku Aya;Morita Shigeki;Tsuda Masumi;Tanaka Shinya;Shinohara Toshiya;Omori Yuko;Sugaya Fumiko;Kato Hiroaki;Narita Yoshiaki;Nakajima Jun;Suzuki Kenji;Takamochi Kazuya;Mano;加藤総夫
• 通讯作者: 加藤総夫

The parabrachial to the central amygdala system regulates long-lasting widespread sensitization in the rodent model of nociplastic pain.?

? 臂旁到中央杏仁核系统调节啮齿动物伤害性疼痛模型中持久广泛的敏化。

• 发表时间: 2022
• 作者: Yajima M;Takahashi Y;Okuda T;Uchiyama S;Sato N;Sugimura YK;Kato F
• 通讯作者: Kato F

What has Made the Central Amygdala So Central in Understanding Non-Thalamic Pain System? - History, Circuits, Translation, and Prospective

是什么使中央杏仁核在理解非丘脑疼痛系统中如此重要？

• 发表时间: 2022
• 作者: 行方和彦;西島義道;北村裕太;本田紗里;郭曉麗;木村敦子;原田知加子;原田高幸.;Kato F.
• 通讯作者: Kato F.

Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain

对乙酰氨基酚和普瑞巴林减弱啮齿动物模型中伤害性广泛疼痛的中枢敏化

• DOI: 10.1016/j.neuropharm.2022.109029
• 发表时间: 2022
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Manami Yajima;Mariko Sugimoto;Yae K.Sugimura;Yukari Takahashi;Fusao Kato
• 通讯作者: Fusao Kato