Evidence map›Paper›PMID 34903165›Full record

ArticleThe journal of headache and pain2021

Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time.

Aimie L Peek, Andrew M Leaver, Sheryl Foster, Nicolaas A Puts, Georg Oeltzschner, Luke Henderson, Graham Galloway, Karl Ng, Kathryn Refshauge, Trudy Rebbeck

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 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

10 authors at 4 institutions in 3 countries.

Aimie L PeekFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia. apee6909@uni.sydney.edu.au.ORCID http://orcid.org/0000-0001-8943-7951
Andrew M LeaverFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia.
Sheryl FosterFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia.
Nicolaas A PutsDepartment of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, Kings College London, London, UK.
Georg OeltzschnerDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Luke HendersonSchool of Medical Sciences, Brain and Mind Centre, University of Sydney, Camperdown, Australia.
Graham GallowayThe University of Queensland, St Lucia, Queensland, 4072, Australia.
Karl NgFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia.
Kathryn RefshaugeFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia.
Trudy RebbeckFaculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, 2141, Australia.
The University of Sydney · AUKennedy Krieger Institute · USKing's College London · GBTranslational Research Institute · AU

Funding

Towards a comprehensive neurometabolic profile in patients with mild cognitive impairment.R00AG062230 · NIA · JOHNS HOPKINS UNIVERSITY · PI OELTZSCHNER, GEORG · 2021 to 2023
$735k
Towards a comprehensive neurometabolic profile in patients with mild cognitive impairment.K99AG062230 · NIA · JOHNS HOPKINS UNIVERSITY · PI OELTZSCHNER, GEORG · 2019 to 2020
$171k
Medical Research Council MR/N026063/1National Health and Medical Research Council APP1079022National Health and Medical Research Council APP1161467NIA NIH HHS K99 AG062230NIA NIH HHS R00 AG062230The University of Sydney SOAR Research Accelerator
6 · The paper itself

Abstract

backgroundAn imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules ("GABA+") using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.

methodsWe observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time.

resultsThe results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = - 0.51, p = 0.03), intensity (r = - 0.51, p = 0.03) and disability (r = - 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8).

conclusionThe correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

Indexed as

Gyrus CinguliMigraine DisordersAustraliagamma-Aminobutyric AcidHumansMagnetic Resonance Spectroscopygamma-Aminobutyric AcidAnti-CGRPGABALongitudinalMigraineMRSPain

Identifiers

PMID34903165
PMCPMC8903525
OpenAlexW4200268257

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.