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.
Highlights
Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation
Orofacial pain elevated N/OFQ expression in trigeminal ganglia (TG) We found that orofacial pain-like behaviors indicated by rat grimace scale (RGS) scores was elicited following tooth movement and started to increase on 1st day, peaked on 3rd day, decreased on 5th day and returned to baseline level on 7th or 14th day (Fig. 2a)
We found that N/OFQ upregulated while UFP-101 downregulated the expression level of Calcitonin gene-related peptide (CGRP) in trigeminal ganglia, supporting the notion that N/OFQ has a pronociceptive role in trigeminal ganglia via promoting CGRP expression and release, facilitating transmission of pain signals
Summary
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. Orofacial pain sensation is initiated at periodontal sensory terminals, modulated at trigeminal ganglia (TG), replayed at trigeminal nucleus and reaches sensory cortex via thalamus [2]. Abundant proteins are upregulated and downregulated in concert to modulate orofacial pain [5, 6]. The receptor of N/OFQ, designated as ORL1, belongs to the opioid receptor family and is widely distributed in both central and peripheral nervous system, especially abundant in pain
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