The Role of Acid-sensing Ion Channel 3 in the Modulation of Tooth Mechanical Hyperalgesia Induced by Orthodontic...

This study aimed to explore the role of acid-sensing ion channel 3 (ASIC3) in the modulation of tooth mechanical hyperalgesia induced by orthodontic tooth movement. In male Sprague-Dawley rats, closed coil springs were ligated between mandibular incisors and molars to mimic orthodontic tooth movement. Bite force was assessed to evaluate tooth mechanical hyperalgesia. The alveolar bone, trigeminal ganglia, and trigeminal nucleus caudalis underwent immunohistochemical staining and immunoblotting for ASIC3. The inferior alveolar nerves were transected to explore the interaction between the periodontal sensory endings and trigeminal ganglia. The role of ASIC3 in trigeminal ganglia was further explored with lentivirus-mediated ASIC3 ribonucleic acid interference. Results showed that ASIC3 was expressed in the periodontal Ruffini endings and expression of ASIC3 protein was elevated in periodontal tissues, trigeminal ganglia, and trigeminal nucleus caudalis, following orthodontic tooth movement. ASIC3 agonists and antagonists significantly aggravated and mitigated tooth mechanical hyperalgesia, respectively. ASIC3 expression decreased after inferior alveolar nerve transection in periodontal tissues. Both in vitro and vivo, the lentivirus vector carrying ASIC3 shRNA inhibited ASIC3 expression and relieved tooth mechanical hyperalgesia. To conclude, ASIC3 is important in the modulation of tooth mechanical hyperalgesia induced by orthodontic tooth movement. Further, the role of ASIC3 in the modulation of pain in periodontal tissues is regulated by trigeminal ganglia. An adjuvant analgesic therapy targeting ASIC3 could alleviate orthodontic movement-associated mechanical hyperalgesia in rats.