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

Authors
  • Yan, Xinyu1
  • Han, Han1
  • Zhang, Shizhen1
  • Lu, Yanzhu1
  • Ren, Linghuan1
  • Tang, Yufei1
  • Li, Xiaolong1
  • Jian, Fan1
  • Wang, Yan1
  • Long, Hu1
  • Lai, Wenli1
  • 1 National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China , Chengdu (China)
Type
Published Article
Journal
BMC Neuroscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Apr 09, 2021
Volume
22
Issue
1
Identifiers
DOI: 10.1186/s12868-021-00632-5
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundNociceptin/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.MethodsOrofacial 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 was 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.ResultsTooth 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.ConclusionsN/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

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