Introduction: Fibromyalgia (FM) is a chronic pain condition characterized by impaired emotional regulation. This study explored the brain response to pain-related fear as a potential brain signature of FM. Methods: We used a conditioned fear task and magnetoencephalography to record pain-related fear responses in patients with FM. Two blocks of 30 fear responses were collected to compute the response strength in the first block and the strength difference between the first and second blocks (fear habituation). These measurements were investigated for their clinical relevance and compared with measurements obtained from healthy controls and patients with chronic migraine (CM), a different chronic pain condition often comorbid with FM. Results: Pain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM (n = 52), patients with CM (n = 50), and the controls (n = 30); the response strength in the first block was consistent across groups. However, fear habituation in the right amygdala decreased in the FM group (vs. CM and control groups, both p ≤ 0.001, no difference between CM and control groups). At the 3-month follow-up, the patients with FM reporting < 30% improvement in pain severity (n = 15) after pregabalin treatment exhibited lower fear habituation in the left amygdala at baseline (vs. ≥ 30% improvement, n = 22, p = 0.019). Receiver operating characteristic analysis confirmed that amygdala fear habituation is a suitable predictor of diagnosis and treatment outcomes of FM (area under the curve > 0.7). Conclusions: Amygdala activation to pain-related fear is maladaptive and linked to treatment outcomes in patients with FM. Because the aberrant amygdala response was not observed in the CM group, this response is a potential brain signature of FM. Trial Registration: ClinicalTrials.gov Identifier, NCT02747940.
- Chronic migraine
- Pain-related fear