Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression. Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

中文翻译：

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N/OFQ 通过 CGRP 依赖性途径调节牙齿移动引起的口面部疼痛


伤害感受肽/孤啡肽 FQ (N/OFQ) 已被证明在口面部疼痛调节中发挥双向作用。降钙素基因相关肽（CGRP）是一种众所周知的促伤害感受分子，参与口面部疼痛的调节。我们的目的是确定 N/OFQ 对口面部疼痛调节和 CGRP 释放的影响。通过在大鼠门牙和磨牙之间结扎弹簧来模拟牙齿移动，建立口面部疼痛模型。测定 N/OFQ 的表达水平并根据口面部疼痛对疼痛水平进行评分。给予N/OFQ受体激动剂和拮抗剂来检查它们对疼痛和三叉神经节(TG)中CGRP表达的影响。此外，基于 N/OFQ 过表达的基因治疗被用来验证 N/OFQ 对疼痛和 CGRP 表达的调节作用。牙齿移动引起口面部疼痛和 N/OFQ 表达升高。 N/OFQ 加剧口面部疼痛并上调 TG 中的 CGRP 表达，而 UFP-101 减轻疼痛并下调 CGRP 表达。基于 N/OFQ 的基因治疗成功地在 TG 中过度表达 N/OFQ，导致 TG 中疼痛加剧和 CGRP 表达升高。 N/OFQ 可能通过上调 CGRP 加剧口面部疼痛。