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

BMC Neurosci. 2021 Apr 9;22(1):25. doi: 10.1186/s12868-021-00632-5.

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 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.

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.

Keywords: CGRP; Nociceptin/OFQ; Orofacial pain; Overexpression; Pain; Tooth Movement; Trigeminal Ganglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism*
  • Disease Models, Animal
  • Facial Pain / etiology
  • Facial Pain / metabolism*
  • Male
  • Nociceptin
  • Opioid Peptides / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Tooth Movement Techniques / adverse effects
  • Trigeminal Ganglion / metabolism*

Substances

  • Calcitonin Gene-Related Peptide
  • Opioid Peptides
  • Nociceptin