Interictal pontine metabolism in migraine patients without aura

Migraine is not associated with altered interictal pontine glutamate levels. Interestingly, interictal total creatine levels were increased in the pons. This novel finding from a Danish imaging study suggests that disequilibrium in the pontine energy metabolism could be an important feature of migraine pathophysiology [1].

The major excitatory neurotransmitter glutamate is involved in the trigeminovascular pain pathway. In the pons, glutamatergic mechanisms are involved in regulating inhibitory descending pain modulation and serotoninergic neurotransmission, as well as modulating the sensory transmission of the trigeminovascular system. Abnormal glutamate levels in the pons may be an important pathophysiological feature of migraine, aiding to attack initiation.

“How to measure glutamate levels in the pons? This is technically challenging,” Dr Samaira Younis (Danish Headache Centre, Denmark) mentioned. “In recent years, however, the application of proton magnetic resonance spectroscopy (MRS) has allowed non-invasive measurements of glutamate in various brain structures.” Using this technique to investigate glutamate at different levels of the trigeminovascular system, previous studies have demonstrated alterations during the interictal state of migraine [2,3]. One study recently investigated glutamate levels in the pons during attacks and detected no change [4].

The current study investigated whether glutamate levels in the pontine are altered outside attack cycles [1]. To this end, 34 patients with migraine without aura were scanned when outside an attack cycle using a proton MRS protocol optimised for the pons at 3T (3T ¹H-MRS).

Measurements were taken on 2 separate days to increase accuracy and they were compared with similar repeated measurements from 16 healthy controls. Results demonstrated that interictal pontine glutamate levels of migraine patients were not different from those of healthy controls (P=0.098; see Figure). “Interestingly, we found that total creatine levels were markedly increased in patients compared with healthy controls (P=0.009; see Figure).” No correlation was found of glutamate or total creatine levels with migraine attack frequency, days since the last attack, disease duration, or usual pain intensity of attacks.

Figure: Glutamate and total creatine levels in migraine patients and healthy controls [1]

1. Younis S, et al. Interictal pontine metabolism in migraine without aura patients: a 3 tesla proton magnetic resonance spectroscopy study. AL066, IHC 2021, 8–12 September.


2. Aguila ME, et al. NMR Biomed. 2015;28(7):890–7.


3. Arngrim N, et al. Brain. 2016;139(Pt 3):723–37.


4. Younis S, et al. J Cereb Blood Flow Metab. 2021;41(3):604–16.

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Posted on 8 November, 20219 February, 2022