Evidence map›Paper›PMID 35382731›Full record

ArticleThe journal of headache and pain2022

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats.

Yanjie Zhou, Lily Zhang, Yuyan Hao, Liu Yang, Shanghua Fan, Zheman Xiao

Open access · goldAbstract read
In one paragraph

Article in The journal of headache and pain, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 37 citations in OpenAlex.

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  8. Evidence for brain glial activity in chronic migraine patients: a [European journal of nuclear medicine and molecular imaging · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Yanjie ZhouDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Lily ZhangDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Yuyan HaoDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Liu YangDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Shanghua FanDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Zheman XiaoDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China. zmxiao@whu.edu.cn.ORCID http://orcid.org/0000-0003-0597-5889
Wuhan University · CN

Funding

National Natural Science Foundation of China 81471133National Natural Science Foundation of China 81971055National Natural Science Foundation of China 82101292
6 · The paper itself

Abstract

backgroundThe incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine.

methodsModel rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation.

resultsMicroglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia.

conclusionsOur results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

Indexed as

Chemokine CX3CL1CX3C Chemokine Receptor 1Migraine DisordersStatus EpilepticusAnimalsHumansMicrogliaRatsThalamusChemokine CX3CL1CX3C Chemokine Receptor 1Cx3cl1 protein, ratCX3CR1 protein, ratBDNFCX3CR1EpilepsyFKNMicrogliaMigraine

Identifiers

PMID35382731
PMCPMC8981829
OpenAlexW4223464262

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.