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 264005, PR China.
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 264005, PR China.
Toxicol Appl Pharmacol. 2021 Mar 1;414:115428. doi: 10.1016/j.taap.2021.115428. Epub 2021 Jan 30.
Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.
研究表明降钙素基因相关肽（CGRP）在疼痛调制中发挥着关键作用。来自外周的伤害性信息通过臂旁核（PBN）传递到与疼痛相关的脑区。本研究旨在探讨 CGRP 和 CGRP 受体在感觉伤害性信息传递中的作用及其机制。采用慢性坐骨神经结扎法建立神经病理性疼痛模型，将 CGRP 和 CGRP8-37 注入大鼠 PBN，用慢病毒包裹的 CLR siRNA 敲低降钙素受体样受体（CLR），即 CGRP 受体的主要结构。采用热板试验（HPT）和 Randall-Selitto 试验（RST）测定大鼠后爪反应潜伏期。采用 RT-PCR 和 Western blot 检测 CLR 的表达。结果显示，PBN 内注射 CGRP 可剂量依赖性地诱导正常大鼠和神经病理性疼痛大鼠产生明显的抗伤害作用，CGRP8-37 注射后 CGRP 诱导的抗伤害作用明显减弱。此外，PBN 中 CLR 的 mRNA 和蛋白表达水平明显降低，神经病理性疼痛大鼠的 CGRP 诱导的抗伤害作用也明显低于正常大鼠。PBN 中 CLR 的敲低降低了 CLR 的表达，CGRP 诱导的抗伤害作用明显降低。综上所述，CGRP 可诱导正常和神经病理性疼痛大鼠 PBN 中的抗伤害作用，CGRP 受体介导了这一作用。神经病理性疼痛导致 PBN 中 CGRP 受体表达减少以及 CGRP 诱导的抗伤害作用减弱。
