Fibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells

Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes. In this study, we created the iMG cells from 14 patients with fibromyalgia and 10 healthy individuals, and compared the activation of iMG cells between two groups at the cellular level. The expression of tumor necrosis factor (TNF)-α at mRNA and protein levels significantly increased in ATP-stimulated iMG cells from patients with fibromyalgia compared to cells from healthy individuals. Interestingly, there was a moderate correlation between ATP-induced upregulation of TNF-α expression and clinical parameters of subjective pain and other mental manifestations of fibromyalgia. These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-α from microglia may be a key factor underlying the complex pathology of fibromyalgia.