Background: Myofascial trigger points (MTrPs) are a highly prevalent source of musculoskeletal pain. Prolonged ongoing nociceptive input from MTrPs may lead to maladaptive changes in the central nervous system. It remains, however, unknown whether pain from MTrPs is associated with brain atrophy. In addition, stress, which may contribute to the formation of MTrPs, is also known to affect brain structures. Here, we address whether structural brain changes occur in patients with chronic pain originating from MTrPs and whether such changes are related to pain or stress. Methods: Voxel-based morphometry was used to compare grey-matter (GM) volumes in 21 chronic pain patients, with MTrPs in the bilateral upper trapezius muscles, with 21 healthy controls. Hyperalgesia was assessed by pressure pain thresholds, and stress was assessed by cortisol levels and anxiety questionnaires. Results: Patients exhibited normal stress levels but lowered pain thresholds. GM atrophy was found in dorsal and ventral prefrontal regions in patients. The GM density of the right dorsolateral prefrontal cortex correlated with pain thresholds in patients, i.e. the more atrophy, the lower pain threshold. GM atrophy was also found in the anterior hippocampus, but the atrophy was neither related to pain nor stress. Conclusions: Patients with chronic myofascial pain exhibit GM atrophy in regions involved in top-down pain modulation and in processing of negative affect. The relationship between the dorsolateral prefrontal cortex and pain thresholds suggests the presence of pain disinhibition. No evidence was found for the involvement of stress. It remains unclear whether the observed atrophy contributes to the development of the chronic pain state or is caused by the ongoing nociceptive input. Significance: Chronic myofascial pain, caused by myofascial trigger points, is associated with localized brain atrophy in areas involved in pain processing and modulation, among others. These findings extend previous knowledge about peripheral and spinal changes to the supraspinal level.