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Antinociceptive Effects of the Adenylyl Cyclase Inhibitor ST034307 on Tooth-Movement-Induced Nociception in Rats

Antinociceptive Effects of the Adenylyl Cyclase Inhibitor ST034307 on Tooth-Movement-Induced Nociception in Rats

Yangfan Cheng, Peina Huang, Bowen Meng, Lei Gan, Dongle Wu, Yang Cao

Arch Oral Biol. 2019 Feb;98:81-86.

PMID: 30465937

Abstract:

Objective:
This study aimed to investigate the antinociceptive effects of the selective adenylyl cyclase type 1 (AC1) inhibitor ST034307 on tooth movement nociception through orofacial nociceptive behavior tests and molecular examination.
Methods:
We placed fixed nickel-titanium alloy closed-coil springs around the incisors of male Sprague-Dawley rats to induce tooth movement. We subsequently administered ST034307 (3 mg/kg), for 2 days, intraperitoneally, and then subjected the rats to a battery of behavioral tests (n = 10/group) to assess orofacial nociception. The changes in the expression of key molecules in the anterior cingulate cortex were measured by ELISA (n = 8/group) and Western blotting (n = 8/group).
Results:
Tooth movement increased face-grooming activities and rat grimace scale scores. Tooth movement was also associated with enhanced cyclic adenosine monophosphate (cAMP) generation as well as protein kinase A (PKA) activation. Moreover, the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and expression of N-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex increased during tooth movement. ST034307 significantly decreased mouth wiping and rat grimace scale scores, accompanied by reductions in cAMP generation, PKA activation, AMPA receptor phosphorylation, and NMDA receptor expression in the anterior cingulate cortex.
Conclusions:
These results suggest that adenylyl cyclase type 1 plays an important role in the development of orthodontic tooth movement nociception. Furthermore, ST034307 can be used as an effective pharmacotherapy for orthodontic nociception.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP133406298	ST034307		133406-29-8	Price

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