The Journal of Headache and Pain · Published 2026-07-15 · DOI 10.1186/s10194-026-02456-2
Rui Wang, Seungho Kim, Hongying Huang, Dafa Shi, Zhongruowen Ren, Changho Choi, Gen Yan, Yongmin Chang, Renhua Wu
Abstract Background Oxidative stress has been implicated in migraine pathophysiology, but direct evidence of brain antioxidant alterations and their relationship to neuronal integrity remains limited. Methods We conducted a cross-sectional proton magnetic resonance spectroscopy (1H-MRS) study measuring seven metabolites in a single thalamic voxel of 131 participants (left or right, selected for spectral quality): 36 healthy controls, 46 migraines without aura, 17 migraines with aura, and 32 tension-type headache patients. Results Glutathione (GSH) was the only metabolite showing significant group differences (Welch’s F = 31.74, p < 0.001, η2 = 0.432). Thalamic GSH was reduced in migraine without aura (1.76 ± 0.16) and migraine with aura (1.70 ± 0.13) compared to healthy controls (2.07 ± 0.20), with large effect sizes (Cohen’s d = 1.70 and 2.14, respectively). N-acetylaspartate (NAA), a marker of neuronal integrity, showed no group differences (p = 0.74). Equivalence testing showed that the GSH-NAA correlation was statistically equivalent to zero within predefined bounds (TOST p = 0.015), indicating that GSH reduction occurred in the absence of a detectable linear association with NAA in this sample. GSH demonstrated good diagnostic performance (AUC = 0.895, 95% CI 0.821–0.952; sensitivity 93.7%; specificity 69.4%), validated by permutation testing (p = 0.001). Conclusions These findings indicate selective thalamic GSH reduction in migraine in the absence of detectable NAA alterations. These observations are consistent with reduced thalamic antioxidant capacity that is not accompanied by measurable neuronal loss, although NAA cannot exclude subtle neuronal or synaptic dysfunction. Thalamic GSH may represent a candidate biomarker that requires independent validation, and the potential of antioxidant strategies remains hypothesis-generating.
Abstract from DOAJ. Public domain (CC0 1.0).
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Wang, R., Kim, S., Huang, H., et al. (2026). Selective reduction of thalamic glutathione in migraine in the absence of detectable N-acetylaspartate alterations. The Journal of Headache and Pain. https://doi.org/10.1186/s10194-026-02456-2