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

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. Gene therapy targeting a pain receptor in nerve cells carrying signals from the jaw could be an effective treatment for the pain associated with orthodontic treatment. Pain triggered by the movement of teeth is a common reason why patients terminate orthodontic treatment early. Previous studies have suggested that tooth movement is associated with an increase in the expression of transient receptor potential vanilloid 1 (TRPV1), a receptor which is activated by various physical and chemical stimuli, triggering pain. In this study, Wenli Lai at Sichuan University and colleagues confirm that TRPV1 expression increases in response to orthodontic forces which coincide with tooth movement pain in rats. They also show that a lentivirus vector can be used to deliver a small interfering RNA molecule that blocks the expression of TRPV1, alleviating pain.