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

Abstract

Background: 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.Methods: 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 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.Results: 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.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

Effect of Postoperative Pain Control in Vibration-assisted Orthodontics: A Systematic Evaluation and Meta-analysis

“…In addition, vibration stimulation down-regulates TRPV1 as well as CGRP levels in periodontal tissue after orthodontic surgery [25]. Numerous studies have focused on calcitonin gene-related peptide (CGRP) as a regulatory target, such as TRPV1, FQ (N/OFQ) [26], etc. CGRP is present in periodontal tissues and it is the most important neuropeptide that promotes pain after orthodontic surgery [25].…”