TY - JOUR
T1 - Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time
AU - Peek, Aimie L.
AU - Leaver, Andrew M.
AU - Foster, Sheryl
AU - Puts, Nicolaas
AU - Oeltzschner, Georg
AU - Henderson, Luke
AU - Galloway, Graham
AU - Ng, Karl
AU - Refshauge, Kathryn
AU - Rebbeck, Trudy
N1 - Funding Information:
This research was funded by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence in recovery following road Traffic Injuries (CRERTI) APP1079022, NHMRC (Career Development Fellowship) APP1161467 and the University of Sydney Research Accelerator (SOAR) Fellowship.
Funding Information:
We would like to acknowledge the research assistants working on the project Mi Hoang Amanda Dinh and Alexis Curtis, and the team at Westmead Hospital Radiology department, Australia. In addition, Edward J. Auerbach, Ph.D. and Ma?gorzata Marja?ska, Ph.D. (Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, USA) for the development of the pulse sequences for the Siemens platform which were provided by the University of Minnesota under a C2P agreement.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Anti-CGRP
KW - GABA
KW - Longitudinal
KW - MRS
KW - Migraine
KW - Pain
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U2 - 10.1186/s10194-021-01352-1
DO - 10.1186/s10194-021-01352-1
M3 - Article
C2 - 34903165
AN - SCOPUS:85121299244
SN - 1129-2369
VL - 22
JO - Journal of Headache and Pain
JF - Journal of Headache and Pain
IS - 1
M1 - 150
ER -