Evidence map›Paper›PMID 32602955›Full record

ReviewHeadache2020

Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review.

Rami Burstein, Andrew M Blumenfeld, Stephen D Silberstein, Aubrey Manack Adams, Mitchell F Brin

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Headache, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 6 pooled it
16.1field-weighted citation impact, top 1% 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

109 citing papers in PubMed, 6 syntheses or guidelines pooled it, 197 citations in OpenAlex.

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  15. Botulinum toxin for chronic migraine.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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49 more citing papers are in PubMed but not listed here.

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 5 institutions in 1 country.

Rami BursteinDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Andrew M BlumenfeldThe Headache Center of Southern California, The Neurology Center, Carlsbad, CA, USA.
Stephen D SilbersteinDepartment of Neurology Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, USA.
Aubrey Manack AdamsAllergan, Inc., Irvine, CA, USA.
Mitchell F BrinAllergan, Inc., Irvine, CA, USA.
Allergan (United States) · USBeth Israel Deaconess Medical Center · USNeurology Center of Southern California · USThomas Jefferson University · USUniversity of California, Irvine · US

Funding

Cortical Mechanisms of Headache: Beyond CSDR01NS094198 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BURSTEIN, RAMI · 2016 to 2020
$1.9M
Allergan, plc, Dublin, IrelandCSR NIH HHS R37-NS0797681CSR NIH HHS RO1-NS094198NINDS NIH HHS R01 NS094198
6 · The paper itself

Abstract

objectiveTo review the literature on the mechanism of action of onabotulinumtoxinA in chronic migraine.

backgroundOnabotulinumtoxinA is a chronic migraine preventive treatment that significantly reduces headache frequency. The traditional mechanism described for onabotulinumtoxinA - reducing muscle contractions - is insufficient to explain its efficacy in migraine, which is primarily a sensory neurological disease.

methodsA narrative literature review on the mechanism of action of onabotulinumtoxinA in chronic migraine.

resultsFollowing injection into tissues, onabotulinumtoxinA inhibits soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE)-mediated vesicle trafficking by cleaving one of its essential proteins, soluble N-ethylmaleimide-sensitive fusion attachment protein (SNAP-25), which occurs in both motor and sensory nerves. OnabotulinumtoxinA inhibits regulated exocytosis of motor and sensory neurochemicals and proteins, as well as membrane insertion of peripheral receptors that convey pain from the periphery to the brain, because both processes are SNARE dependent. OnabotulinumtoxinA can decrease exocytosis of pro-inflammatory and excitatory neurotransmitters and neuropeptides such as substance P, calcitonin gene-related peptide, and glutamate from primary afferent fibers that transmit nociceptive pain and participate in the development of peripheral and central sensitization. OnabotulinumtoxinA also decreases the insertion of pain-sensitive ion channels such as transient receptor potential cation channel subfamily V member 1 (TRPV1) into the membranes of nociceptive neurons; this is likely enhanced in the sensitized neuron. For chronic migraine prevention, onabotulinumtoxinA is injected into 31-39 sites in 7 muscles of the head and neck. Sensory nerve endings of neurons whose cell bodies are located in trigeminal and cervical ganglia are distributed throughout the injected muscles, and are overactive in people with migraine. Through inhibition of these sensory nerve endings, onabotulinumtoxinA reduces the number of pain signals that reach the brain and consequently prevents activation and sensitization of central neurons postulated to be involved in migraine chronification.

conclusionOnabotulinumtoxinA likely acts via sensory mechanisms to treat chronic migraine.

Indexed as

Botulinum Toxins, Type AChronic DiseaseGlutamic AcidHumansMigraine DisordersNeuromuscular AgentsNeuropeptidesNeurotransmitter AgentsSNARE ProteinsBotulinum Toxins, Type AGlutamic AcidNeuromuscular AgentsNeuropeptidesNeurotransmitter Agentsonabotulinum toxin ASNARE Proteinsbotulinumheadachemigrainetrigeminal system

Identifiers

PMID32602955
PMCPMC7496564
OpenAlexW3040027196

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.