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Published in: The Journal of Headache and Pain 1/2021

01-12-2021 | Migraine | Research article

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

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

Published in: The Journal of Headache and Pain | Issue 1/2021

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Abstract

Background

An 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.

Methods

We 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.

Results

The 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).

Conclusion

The 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.
Appendix
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Metadata
Title
Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time
Authors
Aimie L. Peek
Andrew M. Leaver
Sheryl Foster
Nicolaas A. Puts
Georg Oeltzschner
Luke Henderson
Graham Galloway
Karl Ng
Kathryn Refshauge
Trudy Rebbeck
Publication date
01-12-2021
Publisher
Springer Milan
Keyword
Migraine
Published in
The Journal of Headache and Pain / Issue 1/2021
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-021-01352-1

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