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降钙素基因相关肽在未处理大鼠和炎性疼痛大鼠前扣带回皮质伤害性调制中的作用

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain.

作者信息

Hou Ke-Sai, Wang Lin-Lin, Wang Hong-Bo, Fu Feng-Hua, Yu Long-Chuan

机构信息

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.

Neurobiology Laboratory, School of Life Sciences, Peking University, Beijing, China.

出版信息

Front Pharmacol. 2020 Jun 26;11:928. doi: 10.3389/fphar.2020.00928. eCollection 2020.

DOI:10.3389/fphar.2020.00928
PMID:32670060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7332858/
Abstract

It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.

摘要

已知降钙素基因相关肽（CGRP）在大脑的疼痛调节中起关键作用。在扣带回前部皮质（ACC），一种在疼痛调节中重要的脑结构中，CGRP和CGRP受体有高表达。本研究探讨了CGRP和CGRP受体在未处理大鼠和炎症大鼠的ACC伤害性感受调节中的作用及机制。在ACC中给予不同剂量的CGRP在未处理大鼠和有炎性疼痛的大鼠中均以剂量依赖性方式诱导了显著的镇痛作用。在ACC中注射CGRP受体拮抗剂CGRP8 - 37可减弱CGRP诱导的镇痛作用。有趣的是，与未处理大鼠相比，有炎性疼痛大鼠的ACC中CGRP诱导的镇痛作用和CGRP受体表达均降低。通过靶向CGRP受体的小干扰RNA（siRNA）敲低ACC中的CGRP受体可显著减弱大鼠的CGRP受体表达和CGRP诱导的镇痛作用。这些发现表明CGRP和CGRP受体参与大鼠ACC中的伤害性感受调节，抑制CGRP受体表达会导致ACC中CGRP诱导的镇痛作用减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/8a58f67374b8/fphar-11-00928-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/2b86f88dd4c5/fphar-11-00928-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/aa805f9237f0/fphar-11-00928-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/c96cf08c2aee/fphar-11-00928-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/acbd7a579125/fphar-11-00928-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/f4c6e2a2364a/fphar-11-00928-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/8a58f67374b8/fphar-11-00928-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/2b86f88dd4c5/fphar-11-00928-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/ffc7de4ba804/fphar-11-00928-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/aa805f9237f0/fphar-11-00928-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/c96cf08c2aee/fphar-11-00928-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/acbd7a579125/fphar-11-00928-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/f4c6e2a2364a/fphar-11-00928-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ef/7332858/8a58f67374b8/fphar-11-00928-g007.jpg

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Mol Pain. 2019 Jan-Dec;15:1744806919832718. doi: 10.1177/1744806919832718.
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Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25.降钙素/CGRP 肽家族药理学的最新进展：IUPHAR 评论 25。
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