N58A Exerts Analgesic Effect on Trigeminal Neuralgia by Regulating the MAPK Pathway and Tetrodotoxin-Resistant Sodium Channel

Li, Chun-Li; Yang, Ran; Sun, Yang; Feng, Yuan; Song, Yongbo

doi:10.3390/toxins13050357

Cited by 9 publications

(17 citation statements)

References 25 publications

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“…To trace back to the phosphate groups from LRRK2 , LRRK2 pull-down and IP assays of trigeminal root entry zone of TN were conducted to detect a variety of enzymes that catalyze phosphate group transmission. We noticed that MAPK/ERK signaling pathway was the top affected item in TN ( Figure 3(c) ) and was reported to participate in pathogenesis neuralgia in previous studies [ 34 , 35 ]. We harvested ERK1/2 from the LRRK2 binding proteins ( Figure 6(c) ).…”

Section: Resultsmentioning

confidence: 75%

Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model

Wei

Liu

Qiu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by spontaneous and elicited paroxysms of electric-shock-like or stabbing pain in a region of the face. The epigenetic regulation of TN is still obscure. In current study, a rat TN model subject to carbamazepine (CBZ) treatment was established, and transcriptome- and genome-scale profiling of H3K9ac and HDAC3 was performed by RNA-seq and ChIP-seq. We observed that H3K9ac levels in the trigeminal ganglion were lower in the TN rats compared with those in the control, and CBZ treatment led to recovery of H3K9ac levels. Further, we found that HDAC3 was overactivated, which interfered with H3K9 acetylation due to higher phosphorylation in TN compared with that in the control. Finally, the phosphokinase leucine-rich repeat kinase 2 (LRRK2) was demonstrated to contribute to HDAC3 activity via the MAPK signaling pathway. Taken together, we identified a regulatory mechanism in which the phosphate groups transferred from activated ERK and LRRK2 to HDAC3 caused genome-scale deacetylation at H3K9 and resulted in the silencing of a large number of genes in TN. The kinases or important enzymes within this regulatory axis may represent important targets for TN therapy and prevention.

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Section: Resultsmentioning

confidence: 75%

Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model

Wei

Liu

Qiu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…It has been shown that MAPK activation in the spinal cord or primary afferent nerve promotes nociceptor hyperexcitability and induces changes in neuronal plasticity, which is associated with neuropathic and inflammatory pain (Yu et al., 2016 ). As reported, scorpion analgesic peptide N58A exerts significant analgesic effects on CCI‐ION rat models possibly by decreasing the phosphorylation levels of MAPK signaling protein (C. L. Li et al., 2021 ). Additionally, miR‐125a‐3p attenuates the maintenance of orofacial inflammatory pain through negatively regulating p38 MAPK in rat trigeminal ganglions (Y. Dong et al., 2014 ).…”

Section: Discussionmentioning

confidence: 78%

“…reported, scorpion analgesic peptide N58A exerts significant analgesic effects on CCI-ION rat models possibly by decreasing the phosphorylation levels of MAPK signaling protein (C. L Li et al, 2021)…”

mentioning

confidence: 99%

MiR‐223‐3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling

et al. 2022

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Background: Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR-223-3p in mouse models of TN. Methods: Infraorbital nerve chronic constriction injury (CCI-ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR-223-3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI-ION mice was measured using RT-qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR-223-3p and MKNK2 was tested by a luciferase reporter assay. Results: We found that miR-223-3p was downregulated, while MKNK2 was upregulated in TGs of CCI-ION mice. MiR-223-3p overexpression by an intracerebroventricular injection of Lv-miR-223-3p attenuated trigeminal neuropathic pain in CCI-ION mice, as well as reduced the protein levels of pro-inflammatory cytokines in TGs of CCI-ION mice. MKNK2 was verified to be targeted by miR-223-3p. Additionally, miR-223-3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI-ION mice to inhibit MAPK/ERK signaling. Conclusions: Overall, miR-223-3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling.

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“…Many studies have highlighted the effect of disturbances in ion channels on neuropathic pain. This resembles the disturbances observed among NVC patients (Charlesworth et al, 2012;Wei et al, 2013;Choi et al, 2016;Li et al, 2021;Romero et al, 2021). Interestingly, the relationships between disturbances in ion channels and NVC have been explored in a few papers.…”

Section: Disturbances In Ion Channelsmentioning

confidence: 99%

The Underlying Pathogenesis of Neurovascular Compression Syndromes: A Systematic Review

Szmyd

Sołek

Błaszczyk

et al. 2022

Front. Mol. Neurosci.

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Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported. Other syndromes, e.g., disabling positional vertigo, arterial hypertension in the course of NVC at the CN IX-X REZ and torticollis, have insufficient clinical evidence for microvascular decompression. The exact pathomechanism leading to characteristic NVC-related symptoms remains unclear. Proposed etiologies have limited explanatory scope. Therefore, we have examined the underlying pathomechanisms stated in the medical literature. To achieve our goal, we systematically reviewed original English language papers available in Pubmed and Web of Science databases before 2 October 2021. We obtained 1694 papers after eliminating duplicates. Only 357 original papers potentially pertaining to the pathogenesis of NVC were enrolled in full-text assessment for eligibility. Of these, 63 were included in the final analysis. The systematic review suggests that the anatomical and/or hemodynamical changes described are insufficient to account for NVC-related symptoms by themselves. They must coexist with additional changes such as factors associated with the affected nerve (e.g., demyelination, REZ modeling, vasculature pathology), nucleus hyperexcitability, white and/or gray matter changes in the brain, or disturbances in ion channels. Moreover, the effects of inflammatory background, altered proteome, and biochemical parameters on symptomatic NVC cannot be ignored. Further studies are needed to gain better insight into NVC pathophysiology.

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N58A Exerts Analgesic Effect on Trigeminal Neuralgia by Regulating the MAPK Pathway and Tetrodotoxin-Resistant Sodium Channel

Cited by 9 publications

References 25 publications

Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model

Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model

MiR‐223‐3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling

The Underlying Pathogenesis of Neurovascular Compression Syndromes: A Systematic Review

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