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. 2017 Nov 1;10(11):11317-11325.
eCollection 2017.

Emodin inhibits the expression of receptor and calcitonin-gene-related peptide release in trigeminal ganglia of trigeminal neuralgia rats

Wei Xiong  1   2 , Rao-Ping Wu  3   4 , Meng-Xia Tan  3   4 , Zhou-Jie Tong  5 , Ling-Kun He  1 , Shu Guan  3 , Li-Juan Liu  1 , Can-Can Yin  1 , Yu-Lin Shen  3 , Hui-Xiang Ge  3 , Yun Gao  3   6
Affiliations

Emodin inhibits the expression of receptor and calcitonin-gene-related peptide release in trigeminal ganglia of trigeminal neuralgia rats

Wei Xiong et al. Int J Clin Exp Pathol. .

Abstract

Trigeminal neuralgia (TN) is one of the most intense forms of facial pain. It has been reported that the P2X3 receptor plays a crucial role in facilitating pain transmission, and the calcitonin-gene-related peptide (CGRP) from trigeminal ganglia (TGs) might perform differing function in nociceptive afferent input transmission. The present study investigated whether emodin can affect TN pain transmission by suppressing the expression of P2X3 receptors and CGRP in TGs. Chronic constriction injury of the infraorbital branch of the trigeminal nerve (CCI-ION) was used as TN model. The TN rats were randomly divided into the following 4 groups: (1) a sham group (Sham), (2) a sham rats treated with emodin group (TN + E), (3) a TN rats treated with 0.5% sodium carboxymethyl cellulose (CMC) as vehicle group (TN) and (4) a TN rats treated with emodin group (TN + E). The mechanical hyperalgesia threshold of TN rats was tested by Electric Von Frey filaments. The change of the expression of P2X3 receptors and CGRP in rat's TG was detected with RT-PCR, immunohistochemical staining, and Western blotting. The phosphorylation of p38 and ERK1/2 pathway of TG was detected by Western blotting. After CCI-ION injury, the threshold of mechanical hyperalgesia for the territory of ligated infraorbital nerve in TN group decreased significantly compared with that in sham group. On day 14 after operation of CCI-ION, there was also an evident increase in the expression of P2X3 receptors and CGRP in the TG of TN group. However after treatment with emodin, the response of mechanical hyperalgesia of TN rats was clearly increased while the enhanced expression of P2X3 receptor and CGRP in TN rats was significantly decreased. The phosphorylation of p38 and ERK1/2 in TN group was stronger than that in Sham group. But these phosphorylation changes in the TN rats were much weaker after treatment with emodin. In conclusion, P2X3 receptor may cooperate with CGRP in the pain transmission of TN, and emodin can inhibit the expression and activation of P2X3 receptor and CGRP in TG to relieve TN.

Keywords: Emodin; P2X3 receptor; calcitonin-gene-related peptide; trigeminal ganglia; trigeminal neuralgia.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Effect of emodin on the mechanical withdrawal threshold (MWT) of TN rats. The MWT of rats in the four groups was measured. N = 12 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 2
Figure 2
Effects of emodin on the expression of P2X3 receptor at mRNA level in TG. The expression of P2X3 receptor mRNA in TG of each group on postoperative d14 was tested by RT-PCR. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 3
Figure 3
Effects of emodin on the expression of CGRP at mRNA level in TG. The expression of CGRP mRNA in TG of each group on postoperative d14 was tested by RT-PCR. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 4
Figure 4
Effects of emodin on the expression of P2X3 receptor in TG assessed by immunohistochemistry. On postoperative d14, the average optical density of P2X3 staining in TG was measured. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group (arrows indicate the immunostained neurons; scale bars, 100 μm).
Figure 5
Figure 5
Effects of emodin on the expression of CGRP in TG assessed by immunohistochemistry. On postoperative d14, the average optical density of CGRP in TG was measured. N = 6 per group, *P<0.05 vs. sham group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group (arrows indicate the immunostained neurons; scale bars, 100 μm).
Figure 6
Figure 6
Effects of emodin on the expression of P2X3 receptor at protein level in TG. The expression of P2X3 receptor protein in TG of each group on postoperative d14 was determined by Western blotting. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 7
Figure 7
Effects of emodin on the expression of CGRP at protein level in TG. The expression of CGRP protein in TG of each group on postoperative d14 was determined by Western blotting. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 8
Figure 8
Effect of emodin on the phosphorylation of p38 in TG. The expression levels of p38 and p-p38 were detected by Western blotting. Using image analysis, the stain values (integrated optical density) of p-p38 were normalized to individual p38/β-actin. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
Figure 9
Figure 9
Effect of emodin on the phosphorylation of ERK1/2 in TG. The expression levels of ERK1/2 and p-ERK1/2 were detected by Western blotting. Using image analysis, the stain values (integrated optical density) of p-ERK1/2 were normalized to individual ERK1/2/β-actin. N = 6 per group, **P<0.01 vs. sham group; ##P<0.01 vs. TN group.
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