肉毒杆菌毒素 A 通过孤啡肽/强啡肽 Q 通路减轻正畸牙齿移动引起的啮齿类动物口面痛觉。

Botulinum toxin A alleviates orofacial nociception induced by orthodontic tooth movement through nociceptin/orphanin-FQ pathway in rats.

机构信息

Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The Plastic and Cosmetic Center, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Arch Oral Biol. 2020 Sep;117:104817. doi: 10.1016/j.archoralbio.2020.104817. Epub 2020 Jun 12.

DOI:10.1016/j.archoralbio.2020.104817

PMID:32603879

Abstract

OBJECTIVES

To investigate the effect and mechanism of botulinum neurotoxin type A (BoNT/A) in the modulation of orofacial nociception induced by orthodontic tooth movement in rats.

METHODS

An orofacial nociception model was established in male Sprague-Dawley rats by ligating closed-coil springs between incisors and ipsilateral molars. There were two group sets of animals. For the first group set, 120 rats were randomly divided into four groups: no-force group (n = 30), force + saline group (n = 30), force + low dose BoNT/A group (1U/6 μL, n = 30), and force + high dose BoNT/A group (1U/6 μL, n = 30). BoNT/A and saline were injected into periodontal ligament to explore the nociceptive effect of BoNT/A. Ipsilateral trigeminal ganglia (TG) were harvested for detecting the expression levels of nociceptin/orphanin-FQ (N/OFQ). For the second group set, 36 rats were randomly divided into three force groups: BoNT/A + saline group (n = 12), BoNT/A + UFP-101 group (n = 12), and saline + UFP-101 group (n = 12). A potent N/OFQ receptor (NOP) antagonist (UFP-101) was used to examine the role of N/OFQ in BoNT/A-induced antinociception. Tooth-movement nociception level of all groups was evaluated by bite force and rat grimace scale (RGS) at baseline, day 1, day 3, day 5, day 7, day 14.

RESULTS

The behavioral assessments showed the orofacial nociception level in the force + low dose BoNT/A group and force + high dose BoNT/A group were lower than that in the force + saline group. No significant difference was observed in orofacial nociception among no-force group, force + low dose and force + high dose group. The expression levels of N/OFQ in TG were elevated from day 1 and maintained a high level, presenting in descending order among the force + high dose, force + low dose, force + saline and no-force group, respectively. The nociception level of the BoNT/A + UFP-101 group was higher than that of the BoNT/A + saline group. No significant difference was observed between the BoNT/A + UFP-101 group and the saline + UFP-101 group.

CONCLUSIONS

BoNT/A can exert an antinociceptive effect on orofacial nociception induced by tooth movement by stimulating the expression of N/OFQ in TG.

摘要

目的

研究肉毒毒素 A（BoNT/A）在调节正畸牙齿移动引起的啮齿动物口面部疼痛中的作用和机制。

方法

通过结扎门牙和同侧磨牙之间的闭合线圈弹簧，在雄性 Sprague-Dawley 大鼠中建立口面部疼痛模型。动物分为两组。对于第一组，将 120 只大鼠随机分为四组：无张力组（n=30）、张力+盐水组（n=30）、张力+低剂量 BoNT/A 组（1U/6μL，n=30）和张力+高剂量 BoNT/A 组（1U/6μL，n=30）。将 BoNT/A 和盐水注射到牙周韧带中，以探索 BoNT/A 的痛觉效应。收获同侧三叉神经节（TG），检测孤啡肽/孤啡肽原（N/OFQ）的表达水平。对于第二组，将 36 只大鼠随机分为三组：BoNT/A+盐水组（n=12）、BoNT/A+UFP-101 组（n=12）和盐水+UFP-101 组（n=12）。使用一种有效的 N/OFQ 受体（NOP）拮抗剂（UFP-101）来研究 N/OFQ 在 BoNT/A 诱导的镇痛中的作用。所有组在基线、第 1 天、第 3 天、第 5 天、第 7 天和第 14 天通过咬合力和大鼠面部表情量表（RGS）评估牙齿移动性疼痛水平。

结果

行为评估显示，低剂量 BoNT/A 组和高剂量 BoNT/A 组的口面部疼痛水平低于张力+盐水组。无张力组、低剂量和高剂量组之间的口面部疼痛无明显差异。TG 中 N/OFQ 的表达水平从第 1 天开始升高，并保持高水平，分别按高剂量 BoNT/A、低剂量 BoNT/A、张力+盐水和无张力组的顺序排列。BoNT/A+UFP-101 组的疼痛水平高于 BoNT/A+盐水组。BoNT/A+UFP-101 组和盐水+UFP-101 组之间无明显差异。