GABA and glutamate in pediatric migraine

Bell, Tiffany; Stokoe, Mehak; Khaira, Akashroop; Webb, Megan; Noel, Melanie; Amoozegar, Farnaz; Harris, Ashley D.

doi:10.1097/j.pain.0000000000002022

Cited by 26 publications

(25 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, although several MRS studies on thalamic GABA levels have been conducted, and thalamic GABA levels in the controls in the current study were equivalent to those observed by Pollack, 35 the quantitative GABA values were affected by multiple factors, including field strength MRI scanner (3 T, 4 T 34 ), MRS sequence (STEAM, 36 PRESS, MEGA‐PRESS, or JEPSI 34 ), location of MRS VOI (unilateral 37 or bilateral thalamus), post‐process software (LcModel 38 or Gannet), co‐edited macromolecule signals, and internal reference (Cr or water 39 ). For example, only taking internal‐referenced thalamic GABA levels into consideration, the gap in quantitative thalamic GABA values in normal controls in different studies was over 10‐fold 37 .…”

Section: Limitationssupporting

confidence: 76%

Effect ofDRD4Receptor −616 C/G Polymorphism on ThalamicGABALevels in Pediatric Patients With Primary Nocturnal Enuresis

Sun

You

Xue

et al. 2021

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Background The single nucleotide polymorphism (SNP) of dopamine D4 receptor (DRD4) promoter (−616; rs747302) is associated with abnormalities of the thalamus in children suffering from primary nocturnal enuresis (PNE). Purpose To investigate the effect of DRD4 −616 C/G SNP on thalamic gamma‐aminobutyric acid (GABA) levels in PNE children. Study Type Prospective, observational. Subjects One hundred and seventy‐six children with PNE and 161 healthy control children. Field Strength/Sequence 3 T, three‐dimensional T1‐weighted turbo field echo sequence and MEscher–Garwood Point RESolved Spectroscopy (MEGA‐PRESS) MRS sequence. Assessment The MEGA‐PRESS MRS sequence was used to measure thalamic GABA spectra. The thalamic GABA+ level was calculated using the Gannet 3.0 software package for each participant. A questionnaire was used to determine arousal from sleep (AS) scores. Statistical Tests Comparisons of the AS scores and thalamic GABA+ levels were performed using the Mann–Whitney U test between C‐allele carriers and GG homozygotes in the PNE and control groups. Spearman correlation analysis was performed to determine the association between AS scores and thalamic GABA levels in PNE children. Results Thalamic GABA levels in the PNE group were significantly higher than those in the healthy control group (0.178 (0.169–0.186) vs. 0.154 (0.146–0.164), Z = 8.526, Pcorrected < 0.001). The GABA levels in C‐allele carriers were significantly higher than those in GG homozygotes in both the PNE and control groups (0.184 (0.181–0.193) vs. 0.170 (0.165–0.177), Z = 8.683, Pcorrected < 0.001; 0.166 (0.156–0.170) vs. 0.147 (0.141–0.152), Z = 9.445, Pcorrected < 0.001). GABA levels in the thalamus were also significantly and positively correlated with AS scores in C‐allele carriers in the PNE group (r = 0.747, P < 0.05). Data Conclusion DRD4 −616 C allele may be associated with increased thalamic GABA+ levels, especially in C‐allele carrying PNE children. Level of Evidence 2 Technical Efficacy Stage 3

show abstract

Section: Limitationssupporting

confidence: 76%

Effect ofDRD4Receptor −616 C/G Polymorphism on ThalamicGABALevels in Pediatric Patients With Primary Nocturnal Enuresis

Sun

You

Xue

et al. 2021

Magnetic Resonance Imaging

View full text Add to dashboard Cite

show abstract

“…The elevated baseline levels of GABA+ observed in this cohort [ 24 ] and by others [ 14 , 20 , 25 ] have been proposed as a potential cause of migraine, due to being present in people with migraine but not in healthy controls. However, given the cross-sectional nature of the studies, the temporal and directional nature of these findings are unknown.…”

Section: Introductionmentioning

confidence: 51%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…Peek et al demonstrated that improvements in migraine frequency, intensity, and disability are associated with increased GABA+ levels in the anterior cingulate cortex [ 64 ]. Bell et al found that higher glutamate levels in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with longer durations of pediatric migraine [ 10 ]. Additionally, lower GABA levels in the sensorimotor cortex are associated with more frequent migraine attacks [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study

et al. 2022

View full text Add to dashboard Cite

Background The pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects. Methods Using the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine (n = 25), those with chronic migraine (n = 24), and age-matched and sex-matched healthy subjects (n = 16). Patients with chronic migraine were further divided into those with (n = 12) and without (n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University. Results We found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability (r = -0.425, p = 0.055, n = 20), and lower GABA/water (r = -0.424, p = 0.062, n = 20) and Glx/Water (r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality. Conclusions Neurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.

show abstract

GABA and glutamate in pediatric migraine

Abstract: Supplemental Digital Content is Available in the Text. Using magnetic resonance spectroscopy in vivo, we show GABA and glutamate alterations in children aged 7 to 13 years with migraine, which are associated with migraine characteristics.

Cited by 26 publications

References 56 publications

Effect ofDRD4Receptor −616 C/G Polymorphism on ThalamicGABALevels in Pediatric Patients With Primary Nocturnal Enuresis

Effect ofDRD4Receptor −616 C/G Polymorphism on ThalamicGABALevels in Pediatric Patients With Primary Nocturnal Enuresis

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

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study

Contact Info

Product

Resources

About