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

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 1 st day, peaked on the 3 rd day and returned to baseline on the 14 th 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.

TRPV1 and TRPV1-Expressing Nociceptors Mediate Orofacial Pain Behaviors in a Mouse Model of Orthodontic Tooth Movement

“…Indeed, non-steroidal anti-inflammatory drugs (NSAIDs) reduce orthodontic pain in patients and rodents (Bartzela et al, 2009; Shibazaki et al, 2009). Pharmacological inhibition or knockdown of TRPV1 attenuates spontaneous pain behaviors, such as grimace scale or face grooming, induced by orthodontic forces in rats (Gao et al, 2016; Guo et al, 2019a). Our experiments using genetic knockout of TRPV1 further support the contribution of TRPV1 to spontaneous pain behaviors evoked by orthodontic force.…”

“…The role of TRPV1 in non-evoked pain upon the application of orthodontic force was also suggested. Pharmacological inhibition or knockdown of TRPV1 attenuates facial grooming or grimace scale induced by orthodontic force in rats (Gao et al, 2016; Guo et al, 2019a). However, it is not known if TRPV1 contributes to other modalities of orthodontic pain, such as bite-evoked pain.…”

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

“…In addition to pharmaceutical approaches, a recent gene therapy study by Guo et al (2019) using a rat model of orthodontic tooth has shown that reduction of TRPV1 expression in the trigeminal ganglia reduces pain induced by tooth movement in the jaw. In this study, lentivirus containing a TRPV1 shRNA gene was injected into the trigeminal ganglia to reduce TRPV1 protein expression and pain levels were assessed using rat grimace scale (RGS) [50]. RGS is regarded as a proxy to score pain levels in the rats which is assessed by looking the signs of pain from the facial expressions and position of the eyes, ears and mouth of the animal.…”

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

“…The integration of viral gene into host genome on one hand is bene cial for stable expression, which makes it a promising gene therapeutic tool for a variety of pain conditions, especially for chronic pain (53)(54)(55). Our previous study revealed that administration of lentivirus containing shRNA aiming at knocking down TRPV1 or ASIC3 was effective in alleviating orofacial pain (56,57). In our present study, transduction of PNOC overexpression lentivirus was successful in overexpressing N/OFQ in trigeminal ganglia and the overexpression was stable on 3 rd day, 5 th day and 7 th day, but not on 14 th day.…”