Periodontal acidification contributes to tooth pain hypersensitivity during orthodontic tooth movement.

• Acidification is induced in the gingival sulcus of mechanically forced tooth. • Buffering the gingival acidity ameliorates orthodontic mechanical allodynia. • ASIC3 is involved in the mechanical allodynia induced by orthodontic force. • Tooth movement causes ASIC3 phosphorylation in the periodontal tissue. Tooth movements associated with orthodontic treatment often cause tooth pain. However, the detailed mechanism remains unclear. Here, we examined the involvement of periodontal acidification caused by tooth movement in mechanical tooth pain hypersensitivity. Elastics were inserted between the first and second molars to move the teeth in Sprague-Dawley rats. Mechanical head-withdrawal reflex threshold to first molar stimulation and the pH of the gingival sulcus around the tooth were measured. The expression of acid-sensing ion channel 3 (ASIC3) in trigeminal ganglion neurons and phosphorylation of ASIC3 in the periodontal tissue were analyzed. The mechanical head-withdrawal reflex threshold to first molar stimulation and pH in the gingival sulcus decreased on day 1 after the elastic insertion. These decreases recovered to the sham level by buffering periodontal acidification. Periodontal inhibition of ASIC3 channel activity reversed the decreased mechanical head-withdrawal reflex threshold to first molar stimulation. On day 1 after elastic insertion, the tooth movement did not change the number of ASIC3 immunoreactive trigeminal ganglion neurons innervating the periodontal tissue but increased phosphorylated-ASIC3 levels in the periodontal tissue. Periodontal acidification induced by tooth movement causes phosphorylation of ASIC3, resulting in mechanical pain hypersensitivity in mechanically forced tooth. [ABSTRACT FROM AUTHOR]