Inhibitory effects of tetramethylpyrazine on pain transmission of trigeminal neuralgia in CCI-ION rats

• Published in: Brain research bulletin Vol. 134; pp. 72 - 78
• Main Authors: Xiong, Wei, Tan, Mengxia, He, Lingkun, Ou, Xiaoyan, Jin, Youhong, Yang, Guo, Huang, Liping, Shen, Yulin, Guan, Shu, Xu, Changshui, Li, Guilin, Liu, Shuangmei, Xu, Hong, Liang, Shangdong, Gao, Yun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: Adenosine Triphosphate - metabolism; Analgesics, Non-Narcotic - pharmacology; Animals; CCI-ION rats; Disease Models, Animal; HEK293 Cells; Humans; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - pathology; Male; MAP Kinase Signaling System - drug effects; Membrane Potentials - drug effects; Membrane Potentials - physiology; P2X3; p38 Mitogen-Activated Protein Kinases - metabolism; Pain Threshold - drug effects; Pain Threshold - physiology; Phosphorylation - drug effects; Pyrazines - pharmacology; Random Allocation; Rats, Sprague-Dawley; receptor; Receptors, Purinergic P2X3 - genetics; Receptors, Purinergic P2X3 - metabolism; RNA, Messenger - metabolism; Trigeminal ganglion; Trigeminal Ganglion - drug effects; Trigeminal Ganglion - metabolism; Trigeminal Ganglion - pathology; Trigeminal neuralgia; Trigeminal Neuralgia - drug therapy; Trigeminal Neuralgia - metabolism; Trigeminal Neuralgia - pathology; P2X3; Trigeminal neuralgia; receptor; Trigeminal ganglion; CCI-ION rats
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2017.07.005

•Activated P2X3 receptor in TG aggravated pain of TN.•TMP inhibited P2X3 expression of TG.•TMP inhibited ATP currents in HEK293 cells transfected with P2X3.•TMP relieved hyperalgesia of CCI-ION rats. Tetramethylpyrazine (TMP) has anti-inflammatory effects and is used to treat cerebral ischemic injury, but the mechanism of TMP on neural protection is not clear. Trigeminal neuralgia (TN) is a facial pain syndrome that is characterized by paroxysmal, shock-like pain attacks located in the somatosensory distribution of the trigeminal nerve. P2X3 receptor plays a crucial role in facilitating pain transmission. The present study investigates the effects of TMP on trigeminal neuralgia transmission mediated by P2X3 receptor of the trigeminal ganglia (TG). Chronic constriction injury of the infraorbital branch of the trigeminal nerve (CCI-ION) was used as a trigeminal neuralgia model. On day 15 after surgery, there was a significant decline in the mechanical hyperalgesia threshold in the territory of the ligated infraorbital nerve in the TN group, and an increase in expression of P2X3 receptor in the TG of the TN group compared with the Sham group. After treatment with TMP or A-317491, the mechanical hyperalgesia threshold of TN rats was significantly higher, and expression of P2X3 receptor in the TG noticeably declined compared with the TN group. Phosphorylation of p38 and ERK1/2 in the TN group was stronger than in the Sham group. However, the phosphorylation of p38 and ERK1/2 in the TN+TMP group and TN+A-317491 group was much lower than in the TN group. TMP significantly inhibited the ATP activated currents in HEK293 cells transfected with a P2X3 plasmid. Thus, TMP might have inhibitory effects on trigeminal neuralgia by suppressing the expression of P2X3 receptor in the TG and the phosphorylation of p38 and ERK1/2 in the TG.