Evidence map›Paper›PMID 34000998›Full record

ArticleThe journal of headache and pain2021

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice.

Wei-Jia Chen, Jing-Qi Niu, Yi-Ting Chen, Wen-Jing Deng, Ying-Ying Xu, Jing Liu, Wei-Feng Luo, Tong Liu

Open access · goldAbstract read
In one paragraph

Article in The journal of headache and pain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
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  7. Review
  8. BoNT Injection into Temporomandibular Joint Alleviates TMJ Pain in Forced Mouth Opening Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Article
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  14. Article
  15. Progress in study on animal models of trigeminal neuralgia.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Article
  16. Article
  17. Role of microglia in diabetic neuropathic pain.Frontiers in cell and developmental biology · 2024
    Review
  18. Review
  19. Article
  20. Article
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

8 authors at 4 institutions in 1 country.

Wei-Jia Chen *Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
Jing-Qi Niu *Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
Yi-Ting Chen *Changzhou Hygiene Vocational Technology College, Changzhou, 213002, China.
Wen-Jing DengDepartment of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
Ying-Ying XuDepartment of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
Jing LiuDepartment of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
Wei-Feng LuoDepartment of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China. lwfwxx@126.com.
Tong LiuInstitute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, 226019, China. tongliu@ntu.edu.cn.ORCID http://orcid.org/0000-0001-9152-5264
Soochow University · CNChangzhou Vocational Institute of Engineering · CNNantong University · CNUniversity of Science and Technology of China · CN

Funding

Collaborative Innovation Center for Water Treatment Technology and Materials (CN) SS2019060National Natural Science Foundation of China 81671270National Natural Science Foundation of China 81870874
6 · The paper itself

Abstract

objectivesIn this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated.

methodsMale C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2

resultsWe found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice.

conclusionThese results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.

Indexed as

Botulinum Toxins, Type ANeuralgiaTrigeminal NeuralgiaAnimalsAnxietyHyperalgesiaMaleMiceMice, Inbred C57BLRatsRats, Sprague-DawleyToll-Like Receptor 2Botulinum Toxins, Type ATlr2 protein, mouseToll-Like Receptor 2AnxietyBotulinum toxin type AInnate immunityMicrogliaToll-like receptor 2 (TLR2)Trigeminal neuralgia

Identifiers

PMID34000998
PMCPMC8130347
OpenAlexW3162229909

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.