Up-regulation of PKMζ expression in the anterior cingulate cortex following experimental tooth movement in rats

To explore the involvement of synaptic plasticity in pain induced by experimental tooth movement, we evaluated the expression of protein kinase M zeta (PKMζ), an enzyme necessary for maintaining long-term potentiation (LTP) in the anterior cingulate cortex (ACC).

Male Sprague-Dawley rats weighing 250-300g were used. The change of the expression of PKMζ in the ACC was measured by western blot, and the mRNA of PKMζ was detected by quantitative real-time PCR 1, 3, 7 days after experimental tooth movement. The average time spent on mouth-wiping behaviour of rats involved in pain perception was detected. After that a selective PKMζ inhibitor, called myristoylated ζ-pseudosubstrate inhibitory peptide (ZIP) was injected into ACC, and the effects of ZIP were evaluated.

The mouth-wiping behaviour of rats was significantly increased 1, 3, and 7 days after experimental tooth movement. Changes in PKMζ levels were not detected on day 1 but were found to be increased 3 days following the tooth movement, and then declined to the baseline 7 days after tooth movement in the ACC. PKMζ mRNA levels were not significantly different between the experimental and sham-treated groups at the three time points. Time spent on mouth-wiping behaviour was reduced after ZIP was injected into ACC 3 days after tooth movement, and the analgesic effect last for at least 24h.

PKMζ in the ACC acts to maintain the pain induced by experimental tooth movement. Increased expression of PKMζ protein is attributed to persistent translation of PKMζ mRNA. Synaptic plasticity may be involved in the development of tooth movement pain.