The role and mechanism of calcineurin injecting into anterior cingulate cortex in alleviating pain in rats following experimental tooth movement

doi:10.3877/cma.j.issn.1674-1366.2018.02.007

Abstract

Abstract:

Objective

To explore the analgesic effect and mechanism of injection of calcineurin in anterior cingulate cortex (ACC) on experimental tooth movement in rats.

Methods

According to random number table, 60 Sprague-Dawley rats (200-250 g) were randomly divided into four groups: sham group (10) , force group (10) , 0.9% sodium chloride solution group (20) and calcineurin (CaN) solution group (20) . The four groups were treated in different modes: tooth movement modeling but with no force, modeling and applying force, applying force and injecting saline, applying force and injecting CaN. Mouth wiping behaviors and rat grimace scale (RGS) were recorded at the time before brain cannulation surgery in ACC, before modeling, 2 d after modeling and 30 min, 2 h, 4 h, 24 h, 3 d, 5 d and 7 d after injection to assess pain perception in rats. The phosphorylation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluA1 and the expression of phosphorylated protein kinase A (pPKA) and phosphorylated protein kinase Cγ (pPKCγ) were detected with Western blot.

Results

At 2 d after tooth movement, the average mouth wiping time of the sham-operated group and the force group were (43 ± 9) s and (158 ± 21) s, respectively. Besides, the RGS values of these two groups were 19 ± 3 and 53 ± 6, respectively. Compared with the sham-operated group, pain behaviors (t_Mouthwiping= 15.876, P_{Mouth wiping}<0.001; t_RGS= 16.250, P_RGS<0.001) and the expressions of pGluA1-831 and pPKCγ in ACC were both increased in the force group (t₈₃₁= 3.060, P₈₃₁= 0.013; t_PKCγ= 2.831, P_PKCγ= 0.011) . At 2 h, 4 h and 24 h after injection into the ACC area, mean mouth wiping time of CaN solution group was (64 ± 26) , (67 ± 18) , and (93 ± 21) s, respectively, which was significantly less than that in the 0.9% sodium chloride solution group, with average mouth wiping time of (147 ± 31) , (136 ± 29) , (119 ± 30) s, respectively. Meanwhile, at 30 min, 2 h, 4 h, 24 h and 3 d after administration, the RGS values of the CaN solution group were also dramatically lower than those in the 0.9% sodium chloride solution group. In addition, the protein levels of pGluA1-831 and pPKCγ in ACC significantly decreased at 2 h after the injection of calcineurin (t₈₃₁= 7.916, P₈₃₁<0.001; t_PKCγ= 3.230, P_PKCγ= 0.005) .

Conclusions

Pain in rats following orthodontic tooth movement is associated with phosphorylation of AMPA receptor subunit GluA1 at Ser831, which is probably mediated by protein kinase C gamma. Calcineurin alleviates pain of orthodontic tooth movement by dephosphorylation of GluA1.

Key words: Calcineurin, Receptors, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, Toothache, Gyrus cinguli, Tooth movement

Peina Huang, Bowen Meng, Yangfan Cheng, Chufeng Liu, Dongle Wu, Yang Cao. The role and mechanism of calcineurin injecting into anterior cingulate cortex in alleviating pain in rats following experimental tooth movement[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2018, 12(02): 110-117.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhkqyxyjzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1366.2018.02.007

https://zhkqyxyjzz.cma-cmc.com.cn/EN/Y2018/V12/I02/110

Figures/Tables 5

References 21

[1]	Kyrkanides S，Huang H，Faber RD. Neurologic Regulation and Orthodontic Tooth Movement[J]. Front Oral Biol，2016（18）：64-74.
[2]	Long H，Wang Y，Jian F，et al. Current advances in orthodontic pain[J]. Int J Oral Sci，2016，8（2）：67-75.
[3]	Banerjee B，Medda BK，Pochiraju S，et al. AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure[J]. Neurogastroenterol Motil，2013，25（12）：973-e776.
[4]	Miletic G，Hermes JL，Bosscher GL，et al. Protein kinase C gamma-mediated phosphorylation of GluA1 in the postsynaptic density of spinal dorsal horn neurons accompanies neuropathic pain，and dephosphorylation by calcineurin is associated with prolonged analgesia[J]. Pain，2015，156（12）：2514-2520.
[5]	Price TJ，Ghosh S. ZIPping to pain relief：the role（or not）of PKMzeta in chronic pain[J]. Mol Pain，2013（9）：6.
[6]	Kim S，Ziff EB. Calcineurin mediates synaptic scaling via synaptic trafficking of Ca²⁺-permeable AMPA receptors[J]. Plos Biol，2014，12（7）：e1001900.
[7]	Paxinos G，Watson C. The Rat Brain in Stereotaxic Coordinates[M]. 6th ed：Academic Press，2007.
[8]	王少锦，孙彦辉，赵志国，等.大鼠脑立体定向手术校正的三种方法[J].河北医科大学学报，2001，22（2）：75-77.
[9]	Ren Y，Maltha JC，Van′t Hof MA，et al. Age effect on orthodontic tooth movement in rats[J]. J Dent Res，2003，82（1）：38-42.
[10]	Ren Y，Maltha JC，Kuijpers-Jagtman AM. The rat as a model for orthodontic tooth movement--a critical review and a proposed solution[J]. Eur J Orthod，2004，26（5）：483-490.
[11]	Xin Y，Liu X，Cao Y，et al. Up-regulation of PKMζ expression in the anterior cingulate cortex following experimental tooth movement in rats[J]. Arch Oral Biol，2014，59（7）：749-755.
[12]	Long H，Liao L，Gao M，et al. Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats[J]. Neuropeptides，2015（52）：31-37.
[13]	Yang Z，Luo W，Hou J，et al. Development of a behavior model of pain induced by experimental tooth movement in rats[J]. Eur J Oral Sci，2009，117（4）：380-384.
[14]	Liao L，Long H，Zhang L，et al. Evaluation of pain in rats through facial expression following experimental tooth movement[J]. Eur J Oral Sci，2014，122（2）：121-124.
[15]	Sotocinal SG，Sorge RE，Zaloum A，et al. The Rat Grimace Scale：a partially automated method for quantifying pain in the laboratory rat via facial expressions[J]. Mol Pain，2011（7）：55.
[16]	De Rantere D，Schuster CJ，Reimer JN，et al. The relationship between the Rat Grimace Scale and mechanical hypersensitivity testing in three experimental pain models[J]. Eur J Pain，2016，20（3）：417-426.
[17]	Sanderson JL，Gorski JA，Gibson ES，et al. AKAP150-anchored calcineurin regulates synaptic plasticity by limiting synaptic incorporation of Ca²⁺-permeable AMPA receptors[J]. J Neurosci，2012，32（43）：15036-15052.
[18]	Liu SB，Zhang MM，Cheng LF，et al. Long-term upregulation of cortical glutamatergic AMPA receptors in a mouse model of chronic visceral pain[J]. Mol Brain，2015，8（1）：76.
[19]	Miletic G，Lippitt JA，Sullivan KM，et al. Loss of calcineurin in the spinal dorsal horn contributes to neuropathic pain，and intrathecal administration of the phosphatase provides prolonged analgesia[J]. Pain，2013，154（10）：2024-2033.
[20]	Koga K，Descalzi G，Chen T，et al. Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain[J]. Neuron，2015，85（2）：377-389.
[21]	Chen A，Bao C，Tang Y，et al. Involvement of protein kinaseζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity[J]. J Neurophysiol，2015，113（9）：3047-3055.

Please choose a citation manager

Content to export