Abstract
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.
Highlights
Pain and discomfort are the major side effects of orthodontic treatment
Of the green fluorescent protein (GFP)-expressing axonal terminals was various and there was a subpopulation of fine terminals that are presumably unmyelinated C fibers. These results suggest that transient receptor potential vanilloid subtype 1 (TRPV1)-expressing peptidergic afferents constitute a major subset of afferents in the periodontium including Periodontal ligament (PDL) and likely mediate orthodontic pain
To determine the roles of TRPV1 in orthodontic pain, we evaluated Mouse grimace scale (MGS) and bite force (BF) in TRPV1 KO or WT littermates subjected to 10 g orthodontic force (OF) or sham (Figure 7A)
Summary
Pain and discomfort are the major side effects of orthodontic treatment. Fixed orthodontic appliances produce pain in 94% of patients (Scheurer et al, 1996). Pain and soreness induced by orthodontic adjustment peaks after 24 h, and gradually declines, and resolution occurs within a week (Ngan et al, 1989; Scheurer et al, 1996). Pain during biting and chewing peaks after 24 h, creating a major functional discomfort in daily life (Scheurer et al, 1996). Pain management during orthodontic treatment is often not effective, significantly affecting the patient’s compliance to treatment (Sergl et al, 1998). Peripheral and central mechanisms of orthodontic pain are under active investigation (Long et al, 2016) and better understanding of neurobiological mechanisms should help to better manage orthodontic pain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
