LAY ABSTRACTPatients with fibromyalgia have treatment-resistant chronic pain. More research is needed in order to understand how and why fibromyalgia develops. Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, are involved in peripheral and central nervous system development of pain and hyperalgesia, but few studies have examined circulating nerve growth factor and brain-derived neurotrophic factor in fibromyalgia or have investigated whether exercise interventions affect the levels of these peptides. This study compared blood levels of nerve growth factor and brain-derived neurotrophic factor in fibromyalgia with those in healthy controls, and investigated the effect of exercise on these levels. Brain-derived neurotrophic factor levels were higher and levels of nerve growth factor were lower in fibromyalgia, compared with healthy controls. Clinical improvements were achieved following the exercise intervention, but the levels of brain-derived neurotrophic factor and nerve growth factor were not normalized.Background: The pathophysiology of fibromyalgia includes central and peripheral factors. Neurotro phins, such as nerve growth factor and brainderived neurotrophic factor, are involved in peripheral and central nervous system development of pain and hy peralgesia. Few studies have examined circulating nerve growth factor and brainderived neurotrophic factor in fibromyalgia or have investigated whether exercise interventions affect the levels of these pep tides. Objectives: To compare plasma levels of nerve growth factor and brainderived neurotrophic factor in fibromyalgia and in healthy controls, to investiga te correlations between levels of nerve growth fac tor, brainderived neurotrophic factor, and cytokines and clinical variables, and to investigate the effect of exercise on these levels. Subjects and methods: A total of 75 women with fibromyalgia participated in blood tests at baseline and after the 15week intervention, and 25 healthy controls participated at baseline. Patients were ran domized to a 15week progressive resistance exer cise intervention or a relaxation intervention. Results: Brainderived neurotrophic factor level was significantly higher (p < 0.001) and nerve growth factor level was significantly lower (p < 0.001) in fi bromyalgia than in healthy controls. Neither resis tance exercise nor relaxation interventions affec ted the levels of brainderived neurotrophic factor or nerve growth factor. No significant correlations were found between brainderived neurotrophic fac tor or nerve growth factor plasma levels in fibromy algia and cytokine levels or clinical variables. Conclusion: Changes in circulating nerve growth factor and brainderived neurotrophic factor levels may affect nociception/pain in fibromyalgia. Clinical improvements were achieved following the exercise intervention, but the levels of brainderived neuro trophic factor and nerve growth factor were not nor malized.