The evolving landscape and research trend of calcitonin gene-related peptide in migraine: A bibliometric analysis and visualization.

Background: Migraine is a global public health concern, affecting both social and individual well-being. Calcitonin gene-related peptide (CGRP), a crucial neuropeptide, holds important research value in understanding migraine pathogenesis. CGRP receptor antagonists and monoclonal antibodies that target CGRP or its receptors have shown efficacy in reducing migraine frequency and severity, presenting a promising therapeutic approach. This study aimed to conduct a comprehensive bibliometric analysis to analyze the current state, research trends, and future directions of CGRP in migraine. Methods: Bibliometric tools including CiteSpace, VOSviewer, etc., were utilized to extract and summarize publications related to CGRP in migraine from the Web of Science Core Collection Database (WOSCC) between 2004 and 2023, as of December 31, 2023. The analysis focused on trends in annual publications, leading countries/regions and institutions, prominent journals and references, influential authors, and high-frequency keywords in the field. Results: A total of 1,821 articles and reviews involving 5,180 authors from 1,315 organizations across 64 countries were included in the study. These publications were distributed across 362 journals and accumulated 56,999 citations by December 31, 2023. An increasing trend was observed in annual publications on CGRP in migraine. The United States emerged as the leading nation in both publications and citations, with academic Peter Goadsby contributing the highest number of publications. The University of Copenhagen stood out as the institution with the most publications, and Cephalalgia emerged as the most influential journal. The most cited paper identified was "Calcitonin gene-related peptide receptor antagonist BIBN4096BS for the acute treatment of migraine" by Jes Olesen, published in the New Engl Med. Keyword frequency analysis revealed prevalent terms such as "migraine," "CGRP," and "episodic migraine," along with emerging topics represented by keywords including "trial," "monoclonal antibodies," "preventive treatment," and "safety." Conclusion: CGRP is pivotal in migraine pathogenesis, and there is a robust research foundation exploring its role. The US leads in research output on CGRP in migraine. Investigating the mechanism of CGRP and its receptor in migraine remains a key area of interest, particularly focusing on signaling pathways. Future research should target identifying critical therapeutic targets in CGRP antagonist pathways for migraine treatment.

Energy metabolism disturbance in migraine: From a mitochondrial point of view.

Migraine is a serious central nervous system disease with a high incidence rate. Its pathogenesis is very complex, which brings great difficulties for clinical treatment. Recently, many studies have revealed that mitochondrial dysfunction may play a key role in migraine, which affects the hyperosmotic of Ca2+, the excessive production of free radicals, the decrease of mitochondrial membrane potential, the imbalance of mPTP opening and closing, and the decrease of oxidative phosphorylation level, which leads to neuronal energy exhaustion and apoptosis, and finally lessens the pain threshold and migraine attack. This article mainly introduces cortical spreading depression, a pathogenesis of migraine, and then damages the related function of mitochondria, which leads to migraine. Oxidative phosphorylation and the tricarboxylic acid cycle are the main ways to provide energy for the body. 95 percent of the energy needed for cell survival is provided by the mitochondrial respiratory chain. At the same time, hypoxia can lead to cell death and migraine. The pathological opening of the mitochondrial permeability transition pore can promote the interaction between pro-apoptotic protein and mitochondrial, destroy the structure of mPTP, and further lead to cell death. The increase of mPTP permeability can promote the accumulation of reactive oxygen species, which leads to a series of changes in the expression of proteins related to energy metabolism. Both Nitric oxide and Calcitonin gene-related peptide are closely related to the attack of migraine. Recent studies have shown that changes in their contents can also affect the energy metabolism of the body, so this paper reviews the above mechanisms and discusses the mechanism of brain energy metabolism of migraine, to provide new strategies for the prevention and treatment of migraine and promote the development of individualized and accurate treatment of migraine.

[Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology].

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation.

Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

Beneficial Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Ischemic Heart Failure via TGF-ß1/Smad3 Pathway.

Qili qiangxin (QL) capsule is a traditional Chinese medicine that is widely used for the treatment of patients with chronic heart failure (CHF) of all etiologies, although the exact mechanisms of action remain unclear. CHF leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier that may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. We examined whether QL could improve lung injury in ischemic CHF by reducing lung remodeling. Rats with myocardial infarct received QL (1.0 g/kg/day) for 4 weeks. Echocardiographic and morphometric measurements were obtained followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. CHF caused significant lung structural remodeling evidenced by collagen deposition and thickening of the alveolar septa after myocardial infarct that were greatly improved by QL. Lung weight increased after infarct with no evidence of pulmonary edema and was normalized by QL. QL also reduced lung transforming growth factor-ß1 (TGF-ß1), p-Smad3, tumor necrosis factor-α (TNF-α), and Toll-like receptor-4 (TLR4) expression. Thus, QL reduces lung remodeling associated with CHF, mainly by suppressing the TGF-ß1/Smad3 signaling pathway. The mechanism may also involve inhibition of TLR4 intracellular signaling.