Fibromyalgia (FM) is still often viewed as a psychosomatic disorder. However, the increased pain sensitivity to stimuli in FM patients is not an "imagined" histrionic phenomena. Pain, which is consistently felt in the musculature, is related to specific abnormalities in the CNS pain matrix. Brain-derived neurotrophic factor (BDNF) is an endogenous protein involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system (CNS and PNS). Several lines of evidence converged to indicate that BDNF also participates in structural and functional plasticity of nociceptive pathways in the CNS and within the dorsal root ganglia and spinal cord. In the latter, release of BDNF appears to modulate or even mediate nociceptive sensory inputs and pain hypersensitivity. We were interested, if BDNF serum concentration may be altered in FM. The present pilot study assessed to our knowledge for the first time BDNF serum concentrations in 41 FM patients in comparison to 45 age-matched healthy controls. Mean serum levels of BDNF in FM patients (19.6 ng/ml; SD 3.1) were significantly increased as compared to healthy controls (16.8 ng/ml; SD 2.7; p<0.0001). In addition, BDNF serum concentrations in FM patients were independent from age, gender, illness duration, preexisting recurrent major depression and antidepressive medication in low doses. In conclusion, the results from our study indicate that BDNF may be involved in the pathophysiology of pain in FM. Nevertheless, how BDNF increases susceptibility to pain is still not known.