Transient receptor potential Vanilloid 1-based gene therapy alleviates orthodontic pain in rats

Rui Guo,Yang Zhou,Wenli Lai,Zhouqiang Wu,Hu Long,Jing Wen,Di Shan,Huimin Hu,Hong Yang

doi:10.1038/s41368-019-0044-3

Abstract

Orthodontic pain that is induced by tooth movement is an important sequela of orthodontic treatment and has a significant effect on patient quality of life. Studies have shown that the high expression of transient receptor potential vanilloid 1 (TRPV1) in trigeminal ganglions plays a vital role in the transmission and modulation of orofacial pain. However, little is known about the role of TRPV1 in orthodontic pain. In this study, male Sprague–Dawley rats were randomly assigned to six groups to study the role of TRPV1 in the modulation of tooth-movement pain. The expression levels of TRPV1 mRNA and protein were determined by real-time PCR and western blot, respectively. Moreover, pain levels were assessed using the rat grimace scale (RGS). The role of TRPV1 in modulating tooth-movement pain was examined by injecting a TRPV1 antagonist into the trigeminal ganglia of rats. A lentivirus containing a TRPV1 shRNA sequence was constructed and transduced into the rats’ trigeminal ganglia. The results showed that the expression levels of TRPV1 protein and mRNA were elevated following tooth-movement pain. Pain levels increased rapidly on the 1st day, peaked on the 3rd day and returned to baseline on the 14th day. The TRPV1 antagonist significantly reduced tooth-movement pain. The lentivirus containing a TRPV1 shRNA sequence was able to inhibit the expression of TRPV1 and relieved tooth-movement pain. In conclusion, TRPV1-based gene therapy may be a treatment strategy for the relief of orthodontic pain.

Highlights

Pain caused by tooth movement can be perceived during the entire duration of an orthodontic treatment, e.g., separator placement, initial archwire engagement, banding, wearing elastics, rapid maxillary expansion, and debonding, and it can especially be perceived during the initial phases of treatment[1]
Our study shows that transient receptor potential vanilloid 1 (TRPV1) was expressed and functional in the trigeminal ganglia (TG) of healthy rats
The expression of TRPV1 was upregulated by orthodontic forces that coincided with tooth-movement pain in rats, indicating that TRPV1 was involved in orthodontic pain

Summary

Introduction

Pain caused by tooth movement can be perceived during the entire duration of an orthodontic treatment, e.g., separator placement, initial archwire engagement, banding, wearing elastics, rapid maxillary expansion, and debonding, and it can especially be perceived during the initial phases of treatment[1]. It has been shown that 85% of orthodontic patients experience mild to moderate pain, while 9% of them endured severe pain on the first day of treatment[2,3]. Several approaches have been used to alleviate orthodontic pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs), mechanical vibration, laser therapy, and behavioural therapy[6,7,8,9,10,11,12]. None of these studies have shown any of these methods to be truly effective or clinically validated. Studies have shown in a rat neuropathic pain model that the intrathecal injection of siRNA containing the transient receptor potential vanilloid 1 (TRPV1)

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