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Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.