Galectin‐1 Regulates Inflammatory Responses and Promotes Microglial M2 Polarization in Chronic Migraine

Chronic migraine (CM) is a severe and debilitating neurological disorder with an unclear pathophysiology. Galectin-1, a β-galactoside-binding protein, is known for its anti-inflammatory and immune-regulatory effects in various inflammation-related diseases. However, its role in CM has not been fully elucidated. In this study, we analysed data from CM patients and employed a nitroglycerin-induced CM mouse model to explore the potential role of galectin-1. Serum galectin-1 levels were significantly lower in CM patients compared with healthy controls. Additionally, galectin-1 levels were negatively correlated with Visual Analogue Scale (VAS) and Headache Impact Test (HIT-6) scores. CM patients also exhibited elevated levels of IL-6 and TNF-α and reduced levels of IL-10. Notably, galectin-1 levels were inversely correlated with IL-6 and TNF-α and positively correlated with IL-10. In the CM mouse model, galectin-1 expression was significantly reduced in the spinal trigeminal nucleus caudalis (Sp5C) region. Supplementation with galectin-1 significantly increased paw and periorbital mechanical thresholds and reduced light aversion and anxiety-like behaviours. Moreover, galectin-1 enhanced microglial morphology, promoted M2 polarization, reduced the expression of pro-inflammatory factors IL-6 and TNF-α and increased levels of the anti-inflammatory cytokine IL-10. Mechanistically, the effects of galectin-1 on microglia may involve the activation of the PI3K/AKT signalling pathway, as evidenced by increased phosphorylation of PI3K and AKT. In summary, our study demonstrates that galectin-1 plays a crucial role in the pathogenesis of chronic migraine. Exogenous supplementation of galectin-1 effectively alleviates migraine symptoms and promotes microglial M2 polarization, suggesting that galectin-1 may represent a novel therapeutic target for CM.