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

Xiong, Wei; Tan, Mengxi; He, Laichang; Ou, Xiaoyan; Jin, Youhong; Yang, Guo; Huang, Liping; Shen, Yulin; Guan, Shu; Xu, Changshui; Li, Guilin; Liu, Shuangmei; Xu, Hong; Liang, Shangdong; Gao, Yun

doi:10.1016/j.brainresbull.2017.07.005

Cited by 24 publications

(11 citation statements)

References 26 publications

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“…P2X3 receptor and P2X7 receptor belong to the family of purinoceptors for ATP and function as ligand-gated ion channels and may transduce ATP-evoked nociceptor activation [7,8]. Here, we observed an increase in expression of CGRP, P2X3 receptor and P2X7 receptor in TGs from TN model mice, which was consistent with previous studies [8,19].…”

Section: Discussionsupporting

confidence: 92%

“…It is well known that activation of the trigeminal nerve system induces the release of CGRP [15] and blocking of CGRP receptor may be one of the ways to treat TN [18]. The P2X3 receptor and P2X7 receptor play a crucial role in facilitating pain transmission in TN [7,19,20]. P2X3 receptor and P2X7 receptor belong to the family of purinoceptors for ATP and function as ligand-gated ion channels and may transduce ATP-evoked nociceptor activation [7,8].…”

Section: Discussionmentioning

confidence: 99%

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Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

Yan

Zhu

et al. 2020

J Inflamm

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Background: This study aims to investigate the role of long non-coding RNA Gm14461 in regulating pain transmission in trigeminal neuralgia (TN). The mouse TN model was produced by chronic constriction injury of the infraorbital nerve (CCI-ION). The values of mechanical withdrawal threshold (MWT) were measured to assess the nociception of mice at different times after CCI-ION surgery (0, 1, 3, 5, 7, 9, 11, 13, 15 d). The primary mouse trigeminal ganglion neurons (TGNs) were isolated from C57BL/6 J mice and treated with TNF-α to mimic a TN cellular model. The expression of Gm14461, TNF-α, IL-1β, and IL-6 was examined using qRT-PCR. The protein levels of CGRP and P2X3/7 receptor were measured using western blot.Results: Gm14461 expression was increased in trigeminal ganglia (TGs) of TN mice on the operation side. Furthermore, Gm14461 knockdown in TGs increased, whereas Gm14461 overexpression decreased MWT in TN mice. Moreover, Gm14461 knockdown downregulated, whereas Gm14461 overexpression upregulated mRNA levels of TNF-α, IL-1β, and IL-6 and protein levels of CGRP and P2X3/7 receptor in TGs from TN mice. In vitro assay showed that Gm14461 was upregulated by TNF-α, IL-1β, and IL-6. Additionally, Gm14461 knockdown decreased protein levels of CGRP and P2X3/7 receptor in TNF-α-treated TGNs, whereas Gm14461 overexpression exerted the opposite effect.Conclusion: Gm14461 promoted pain transmission (reduced MWT value) in a CCI-ION-induced mouse TN model. The underlying mechanisms might involve the regulation of pro-inflammatory cytokines, CGRP and P2X3/7 receptor.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

Yan

Zhu

et al. 2020

J Inflamm

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“…Although our present results showed that ligustrazine enhanced the hypnotic and analgesic effect of ketamine in mice, whether it has the same effect in human remained unknown. In the rat models of neuropathic pain 53,54) and trigeminal neuralgia, 55) ligustrazine showed inhibitory effects on pain transmission. Our present results did not find ligustrazine alone have analgesic roles.…”

Section: Discussionmentioning

confidence: 98%

Ligustrazine Enhances the Hypnotic and Analgesic Effect of Ketamine in Mice

Liu

Huang

et al. 2018

Biological & Pharmaceutical Bulletin

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The purpose of this study was to determine the effects of different concentrations of ligustrazine, an extract from Chinese herb, on ketamine requirement for hypnosis and analgesia in mice. In the hypnotic response study, mice were randomly allocated to receive saline or ligustrazine at 10, 20, 40, 80 or 160 mg·kg by intraperitoneal injection. Ketamine was administrated 15 min after ligustrazine injection. The hypnotic response was determined by assessing loss of the righting reflex (LORR) after ketamine injection. The dose of ketamine was determined by modified Dixon's up-and-down method in each group. In the analgesia study, different doses of ligustrazine were administrated 15 min before 50 mg·kg ketamine injection. The analgesia effects (pain threshold) were determined by heat radiation-induced tail-flick latency and evaluated before ligustrazine administration or 5, 15, 30 and 60 min after ketamine administration. The ED [95% confidence interval (CI)] for hypnosis induced by ketamine was 54.1 (44.8, 65.3) mg·kg. Ligustrazine dose-dependently decreased the ED for ketamine to induce hypnosis, which was [31.6 (26.2, 38.1)] mg·kg with the addition of 80 mg·kg ligustrazine and [27.7 (22.6, 33.7)] mg·kg with the addition of 160 mg·kg ligustrazine, respectively (p<0.05). Ligustrazine at 160 mg·kg also increased pain threshold in the presence of ketamine. Ligustrazine enhanced the hypnotic effect of ketamine in a dose-dependent manner. Ligustrazine at a large dose also increased the analgesic effect of ketamine.

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“…However, there is little evidence that such treatments result in 50% pain reduction and improvement in quality of life . Targeted therapy has been recognized as an attractive therapeutic strategy for the treatment of TN with high safety and efficacy, and protein kinases have been considered as one of the most promising targets in the targeted TN therapy . The human genome encodes 538 protein kinases that transfer a γ‐phosphate group from ATP to serine, threonine, and tyrosine residues; many of them are associated with human disease initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

“…3 Targeted therapy has been recognized as an attractive therapeutic strategy for the treatment of TN with high safety and efficacy, 4 and protein kinases have been considered as one of the most promising targets in the targeted TN therapy. 5 The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, and tyrosine residues 6 ; many of them are associated with human disease initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of neurological disorder has proven successful in clinical therapy.…”

Section: Introductionmentioning

confidence: 99%

Statistical analysis and heuristic identification of unexpected interactions from the neurokinase‐inhibitor interactome in trigeminal neuralgia pharmacological intervention

Liu

Chen

Liu

et al. 2019

Journal of Chemometrics

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The cell signaling pathways of human trigeminal neuralgia (TN) are orchestrated by a variety of protein kinase‐elicited phosphorylation events. However, a majority of TN‐related neurokinases have not yet been revealed and still remain largely unexplored. Here, a systematic kinase‐inhibitor interactome for 601 small‐molecule inhibitors across 51 human neurokinases is created via a high‐throughput molecular docking procedure; the inhibitors are reversible, ATP competitive, and commercially available, while the kinases are enriched by gene ontology (GO) to be semantically relevant with TN and have cocrystallized structures with their cognate ligands. Heuristic clustering and statistical analysis identify 35 hit inhibitors from the interactome profile, which are potential to target TN‐related kinases. The intermolecular interactions of four promising inhibitors with the array of 51 TN‐related kinases are investigated in detail at molecular level using dynamics simulation and energetics analysis. Consequently, a total of nine protein kinases are inferred as high‐affinity cotargets of these potent inhibitors, in which fours have already been established as sophisticated targets for TN therapy, while others are still unclear about their therapeutic implications underlying the disease. Some candidates are selected as representatives to perform kinase assay. It is found that some putative kinase targets can be inhibited effectively by noncognate inhibitors; the activity values are comparable with or even better than known cognate inhibitors. Structural examination of a potent kinase‐inhibitor complex identifies a number of noncovalent interactions such as hydrogen bonds, cation‐π stacking, and hydrophobic contacts at the tightly packed complex interface, conferring both stability and specificity to the complex recognition and interaction.

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

Cited by 24 publications

References 26 publications

Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

Ligustrazine Enhances the Hypnotic and Analgesic Effect of Ketamine in Mice

Statistical analysis and heuristic identification of unexpected interactions from the neurokinase‐inhibitor interactome in trigeminal neuralgia pharmacological intervention

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