Elisabetta Abenavoli 1,* , Valentina Berti 2 , Matilde Nerattini 2, Piercarlo Sarzi-Puttini 3,4, Georgios Filippou 3,4 , Alessandro Lucia 5, Gilberto Pari 6, Stefano Pallanti 7,8, Fausto Salaffi 9, Marina Carotti 10, Silvia Sirotti 3,4
and Francesco Porta 6
Abstract: Fibromyalgia syndrome (FMS) is a complex, heterogeneous disorder characterized by chronic widespread pain, fatigue, and cognitive disturbances. The multifactorial nature of FMS, with the involvement of central and peripheral mechanisms, hampers diagnosis and effective treatment. In recent years, positron emission tomography (PET) imaging has emerged as a valuable tool for exploring the neurobiological underpinnings of FMS. Several studies have investigated alterations in glucose metabolism, neurotransmitter systems (including opioid, dopamine, and GABAergic pathways), and neuroinflammation using various PET tracers. These findings have revealed distinct brain metabolic and molecular patterns in FMS patients compared to healthy controls, particularly in painrelated regions such as the thalamus, insula, and anterior cingulate cortex (ACC). Moreover, preliminary data suggest that PET imaging may help identify FMS subgroups with different pathophysiological profiles, potentially allowing for tailored therapeutic approaches. This review summarizes the current evidence on PET applications in FMS and discusses the potential role of molecular imaging in improving patient stratification and predicting treatment response.
