PMID- 33836649 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20231213 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 22 IP - 1 DP - 2021 Apr 9 TI - N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways. PG - 25 LID - 10.1186/s12868-021-00632-5 [doi] LID - 25 AB - 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. FAU - Yan, Xinyu AU - Yan X AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Han, Han AU - Han H AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Zhang, Shizhen AU - Zhang S AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Lu, Yanzhu AU - Lu Y AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Ren, Linghuan AU - Ren L AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Tang, Yufei AU - Tang Y AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Li, Xiaolong AU - Li X AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Jian, Fan AU - Jian F AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Wang, Yan AU - Wang Y AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. FAU - Long, Hu AU - Long H AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. hlong@scu.edu.cn. FAU - Lai, Wenli AU - Lai W AUID- ORCID: 0000-0002-7652-739X AD - Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Center for Oral Research, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, 610041, China. wenlilai@scu.edu.cn. LA - eng GR - No. 82071147/National Natural Science Foundation of China/ GR - Nos. 2018JY0558, 2021YJ0428 & 2018SZ0232/Sichuan Science and Technology Program/ GR - Nos. 19PJ233 and 20PJ090/Research Grant of Health Commission of Sichuan Province/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210409 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (Opioid Peptides) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Animals MH - Calcitonin Gene-Related Peptide/*metabolism MH - Disease Models, Animal MH - Facial Pain/etiology/*metabolism MH - Male MH - Opioid Peptides/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/physiology MH - Tooth Movement Techniques/adverse effects MH - Trigeminal Ganglion/*metabolism MH - Nociceptin PMC - PMC8034138 OTO - NOTNLM OT - CGRP OT - Nociceptin/OFQ OT - Orofacial pain OT - Overexpression OT - Pain OT - Tooth Movement OT - Trigeminal Ganglia COIS- The authors declare that they have no competing interests. EDAT- 2021/04/11 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/04/09 CRDT- 2021/04/10 05:20 PHST- 2020/06/04 00:00 [received] PHST- 2021/03/26 00:00 [accepted] PHST- 2021/04/10 05:20 [entrez] PHST- 2021/04/11 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/04/09 00:00 [pmc-release] AID - 10.1186/s12868-021-00632-5 [pii] AID - 632 [pii] AID - 10.1186/s12868-021-00632-5 [doi] PST - epublish SO - BMC Neurosci. 2021 Apr 9;22(1):25. doi: 10.1186/s12868-021-00632-5.