Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine

Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide. Its activity has been associated with several molecular processes involved in migraine. Therefore, this cross-sectional study aims to study the potential role of aSMase in patients with episodic and chronic migraine. In this cross-sectional pilot study, serum samples from female healthy controls (n = 23), episodic migraine (EM) patients (n = 31), and chronic migraine (CM) patients (n = 28) were studied. The total serum levels of aSMase were determined by ELISA. In addition, the serum levels of sphingomyelin (SM), dihydro-sphingomyelin (dhSM), ceramide (Cer), and dihydro-ceramide (dhCer) were determined by mass spectrometry as biomarkers involved in the main molecular pathways associated with aSMase. aSMase serum levels were found significantly elevated in both EM (3.62 ± 1.25 ng/mL) and CM (3.07 ± 0.95 ng/mL) compared with controls (1.58 ± 0.72 ng/mL) (<i>p</i> < 0.0001). ROC analysis showed an area under the curve (AUC) of 0.94 (95% CI: 0.89-0.99, <i>p</i> < 0.0001) and 0.90 (95% CI: 0.81-0.99, <i>p</i> < 0.0001) for EM and CM compared to controls, respectively. Regarding other biomarkers associated with aSMase's pathways, total SM serum levels were significantly decreased in both EM (173,534 ± 39,096 pmol/mL, <i>p</i> < 0.01) and CM (158,459 ± 40,010 pmol/mL, <i>p</i> < 0.0001) compared to the control subjects (219,721 ± 36,950 pmol/mL). Elevated serum levels of aSMase were found in EM and CM patients compared to the control subjects. The decreased SM levels found in both EM and CM indicate that aSMase activity plays a role in migraine. Therefore, aSMase may constitute a new therapeutic target in migraine that should be further investigated.