PMID- 31620023 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 10 DP - 2019 TI - TRPV1 and TRPV1-Expressing Nociceptors Mediate Orofacial Pain Behaviors in a Mouse Model of Orthodontic Tooth Movement. PG - 1207 LID - 10.3389/fphys.2019.01207 [doi] LID - 1207 AB - Orthodontic force produces mechanical irritation and inflammation in the periodontium, which is inevitably accompanied by pain. Despite its prevalence, treatment of orthodontic pain is ineffective. Elucidating underlying neural mechanisms is critical to improving the management of orthodontic pain. We have assessed the contribution of transient receptor potential vanilloid subtype 1 (TRPV1) and the TRPV1-expressing subset of nociceptive afferents to pain behaviors induced by orthodontic force in mice. Microfocus X-ray computed tomography analysis showed that application of an orthodontic force of 10 g to the maxillary first molar produced reliable tooth movement in mice. Mouse grimace scale (MGS) was evaluated as an indication of non-evoked spontaneous pain and bite force (BF) was measured for assessing bite-evoked nocifensive behaviors. Orthodontic force increased MGS and decreased BF, both of which were interpreted as increased levels of pain. These behaviors peaked at 1d and returned near to the sham level at 7d. Retrograde labeling and immunohistochemical assays showed TRPV1-expressing peptidergic afferents are abundantly projected to the periodontium. Direct injection of resiniferatoxin into trigeminal ganglia (TG) decreased TRPV1-expressing afferents by half in the targeted region of TG. The chemical ablation of TRPV1-expressing afferents significantly attenuated orthodontic pain behaviors assessed by MGS and BF. Consistently, the knockout of TRPV1 also attenuated orthodontic force-induced changes in MGS and BF. These results suggest that TRPV1 and TRPV1-expressing trigeminal nociceptors constitute a primary pathway mediating orthodontic pain behaviors in mice. This model will be useful for mechanistic studies on orthodontic pain aimed at developing novel approaches for painless orthodontics. CI - Copyright (c) 2019 Wang, Kim, Ali, Ong, Pae and Chung. FAU - Wang, Sheng AU - Wang S AD - Program in Neuroscience, Center to Advance Chronic Pain Research, Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, United States. FAU - Kim, Martin AU - Kim M AD - Program in Neuroscience, Center to Advance Chronic Pain Research, Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, United States. FAU - Ali, Zayd AU - Ali Z AD - Program in Neuroscience, Center to Advance Chronic Pain Research, Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, United States. FAU - Ong, Katherine AU - Ong K AD - Program in Neuroscience, Center to Advance Chronic Pain Research, Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, United States. FAU - Pae, Eung-Kwon AU - Pae EK AD - Department of Orthodontic and Pediatric Dentistry, School of Dentistry, University of Maryland, Baltimore, MD, United States. FAU - Chung, Man-Kyo AU - Chung MK AD - Program in Neuroscience, Center to Advance Chronic Pain Research, Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, United States. LA - eng GR - R01 DE023846/DE/NIDCR NIH HHS/United States GR - R01 DE027731/DE/NIDCR NIH HHS/United States PT - Journal Article DEP - 20190920 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 EIN - Front Physiol. 2019 Oct 22;10:1353. PMID: 31695629 PMC - PMC6763553 OTO - NOTNLM OT - TRPV1 OT - behavioral assays OT - orthodontic tooth movement OT - peptidergic nociceptors OT - periodontium OT - trigeminal ganglia EDAT- 2019/10/18 06:00 MHDA- 2019/10/18 06:01 PMCR- 2019/09/20 CRDT- 2019/10/18 06:00 PHST- 2019/05/21 00:00 [received] PHST- 2019/09/04 00:00 [accepted] PHST- 2019/10/18 06:00 [entrez] PHST- 2019/10/18 06:00 [pubmed] PHST- 2019/10/18 06:01 [medline] PHST- 2019/09/20 00:00 [pmc-release] AID - 10.3389/fphys.2019.01207 [doi] PST - epublish SO - Front Physiol. 2019 Sep 20;10:1207. doi: 10.3389/fphys.2019.01207. eCollection 2019.