Evidence map›Paper›PMID 37085778›Full record

ArticleThe journal of headache and pain2023

Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.

Xiaoxu Zeng, Jia Mai, Hongjian Xie, Ling Yang, Xiaojuan Liu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Xiaoxu ZengDepartment of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Jia MaiDepartment of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Hongjian XieDepartment of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Ling YangDepartment of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Xiaojuan LiuDepartment of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China. 525623699@qq.com.
West China Second University Hospital of Sichuan University · CNSichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCentral sensitization has been widely accepted as an underlying pathophysiological mechanism of chronic migraine (CM), activation of cannabinoid type-1 receptor (CB1R) exerts antinociceptive effects by relieving central sensitization in many pain models. However, the role of CB1R in the central sensitization of CM is still unclear.

methodsA CM model was established by infusing inflammatory soup (IS) into the dura of male Wistar rats for 7 days, and hyperalgesia was assessed by the mechanical and thermal thresholds. In the periaqueductal gray (PAG), the mRNA and protein levels of CB1R and hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2) were measured by qRT-PCR and western blotting. After intraventricular injection of Noladin ether (NE) (a CB1R agonist), ZD 7288 (an HCN2 blocker), and AM 251 (a CB1R antagonist), the expression of tyrosine phosphorylation of N-methyl-D-aspartate receptor subtype 2B (pNR2B), calcium-calmodulin-dependent kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (pCREB) was detected, and central sensitization was evaluated by the expression of calcitonin gene-related peptide (CGRP), c-Fos, and substance P (SP). Synaptic-associated protein (postsynaptic density protein 95 (PSD95) and synaptophysin (Syp)) and synaptic ultrastructure were detected to explore synaptic plasticity in central sensitization.

resultsWe observed that the mRNA and protein levels of CB1R and HCN2 were both significantly increased in the PAG of CM rats. The application of NE or ZD 7288 ameliorated IS-induced hyperalgesia; repressed the pNR2B/CaMKII/pCREB pathway; reduced CGRP, c-Fos, SP, PSD95, and Syp expression; and inhibited synaptic transmission. Strikingly, the application of ZD 7288 relieved AM 251-evoked elevation of pNR2B, CGRP, and c-Fos expression.

conclusionsThese data reveal that activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in CM rats. The activation of CB1R might have a positive influence on the prevention of CM by mitigating central sensitization.

Indexed as

Central Nervous System SensitizationMigraine DisordersReceptor, Cannabinoid, CB1Receptors, N-Methyl-D-AspartateAnimalsCalcitonin Gene-Related PeptideCalcium-Calmodulin-Dependent Protein Kinase Type 2GlyceridesHyperalgesiaHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMalePotassium ChannelsPyrimidinesRatsRats, WistarReceptors, CannabinoidCalcitonin Gene-Related PeptideCalcium-Calmodulin-Dependent Protein Kinase Type 2Cnr1 protein, ratGlyceridesHcn2 protein, ratHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsICI D2788noladin etherNR2B NMDA receptorPotassium ChannelsPyrimidinesReceptor, Cannabinoid, CB1Receptors, CannabinoidReceptors, N-Methyl-D-AspartateCannabinoid receptorCentral sensitizationChronic migraineHCNNR2B

Identifiers

PMID37085778
PMCPMC10120244
OpenAlexW4366742536

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.