Fibromyalgia (FM) is a disabling idiopathic chronic pain condition characterized by emotional dysregulation; however, few studies have explored the functional changes of the limbic system or neural substrates of emotional processing in patients with FM.

Innovative methods involving magnetoencephalography and a conditioned fear task were used to obtain direct neural activity from the amygdala to advance current understanding of pain-related fear in FM and chronic migraine (CM); response to pregabalin treatment in patients with FM was followed to verify the amygdala fear response as a potential brain signature for FM diagnosis and prognosis.

Pain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM, those with CM, and controls. Notably, fear habituation in the right amygdala decreased in the patients with FM (vs. those with CM and controls); no difference was detected between the patients with CM and controls.

After 3 months of pregabalin treatment, the patients with FM patients who reported ≥ 30% improvement in pain severity exhibited a higher degree of fear habituation in the left amygdala relative to those who reported < 30% pain improvement.

Receiver operating characteristic analysis confirmed that amygdala fear habituation is a suitable predictor of diagnosis and treatment outcomes of FM.