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. 2021 Aug;9(16):1318.
doi: 10.21037/atm-21-3423.

Effects of ligustrazine on the expression of neurotransmitters in the trigeminal ganglion of a rat migraine model

Hui Li  1 , Fanghui Bai  2 , Cong Cong  3 , Baotian Chen  4 , Wei Xie  4 , Shasha Li  5 , Qiang Liu  4 , Chaojun Chen  6 , Yanhua Wu  1
Affiliations

Effects of ligustrazine on the expression of neurotransmitters in the trigeminal ganglion of a rat migraine model

Hui Li et al. Ann Transl Med. 2021 Aug.

Abstract

Background: Migraine is one of the most common neurological diseases which has been treated by active substances from traditional Chinese medicine (TCM), such as ligustrazine, an extract of the Chinese herb Chuanxiong. However, the pathogenesis of migraine and the curative mechanisms of ligustrazine have remained unclear. The genes P2X3, TRPV1, ERK, and c-fos have been implicated to play a role. In this work, we attempted to elucidate the analgesic mechanism of ligustrazine using a classic migraine-representative rat model.

Methods: The migraine rat model was established by administration of nitroglycerin (NTG). Ligustrazine treatment was administered by intravenous injection. The animal's behavior was continuously recorded, and then trigeminal ganglions (TGs) were isolated. Total RNA was extracted from cells and total protein was extracted from TG. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the levels of P2X3, TRPV1, c-Fos, and ERK in TG.

Results: Ligustrazine could reduce the neurological activities of NTG-induced migraine rats. The rats TG nerve showed varying degrees of expression of P2X3, TRPV1, c-Fos and ERK expression element. Ligustrazine could inhibit over-expression of P2X3, TRPV1, c-fos, and ERK in the TG nerve of NTG-induced migraine rats.

Conclusions: Our results demonstrated that ligustrazine had potent activity against NTG-induced migraine rats through inhibition of the c-fos/ERK signaling pathway. This work may provide a comprehensive basis for a better understanding of the pathogenesis of migraine and the curative mechanisms of ligustrazine.

Keywords: Migraine; ligustrazine; neurotransmitters; trigeminal ganglion (TG).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3423). The authors report funding support from the National Natural Science Foundation of China (81774239). The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
HPLC chromatogram of Ligustrazine hydrochloride injection. HPLC, high performance liquid chromatography.
Figure 2
Figure 2
Intergroup comparison of the climbing cage frequency and scratching head frequency of each time point. (A) Intergroup comparison of the climbing cage frequency of each time; (B) intergroup comparison of the scratching head frequency of each time. TMP, tetramethylpyrazine.
Figure 3
Figure 3
Effects of TMP on the expression of P2X3 and TRPV1 in TG. (A) Representative immunofluorescence staining results of P2X3: (A1), control group; (A2), model group; (A3), TMP group (×200); (B) representative immunofluorescence staining results of TRPV1: (B1), control group; (B2), model group; (B3), TMP group (×200); (C) mRNA levels of P2X3; (D) mRNA levels of TRPV1; mRNA levels were quantified by qRT-PCR analysis. One-way ANOVA was used for multiple comparisons. All data are presented as mean ± SD (n=3). Compared with model group: **P<0.01; (E) the results of proteins expression of P2X3; (F) the analysis of proteins expression of P2X3, compared with model group: **P<0.01; (G) the results of proteins expression of TRPV1; (H) the analysis of proteins expression of TRPV1, compared with model group: **P<0.01. TMP, tetramethylpyrazine; TG, trigeminal ganglion; mRNA, messenger RNA; qRT-PCR, quantitative real-time polymerase chain reaction; ANOVA, analysis of variance; SD, standard deviation.
Figure 4
Figure 4
Effects of TMP on the expression of c-fos receptors in TG of each group. Representative immunofluorescence staining results of c-fos. (A) Control group; (B) model group; (C) TMP group (×200). TG, trigeminal ganglion; TMP, tetramethylpyrazine.
Figure 5
Figure 5
Effects of TMP on the expression of ERK protein in TG of each group. (A) Bands of proteins of p-ERK, ERK were detected by WB; (B) the analysis results of proteins expression of p-ERK/ERK. Compared with model group: **P<0.01. TG, trigeminal ganglion; TMP, tetramethylpyrazine; WB, western blot.
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