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We used PET to study regional cerebral blood flow (rCBF) changes in nine patients with unilateral central pain after a lateral medullary infarct (Wallenberg's syndrome). All patients presented, on the abnormal side, a combination of hypaesthesia to noxious and thermal stimuli and allodynia to rubbing of the skin with a cold object (i.e. abnormal pain to innocuous stimulation). The rCBF responses during allodynia were compared with those obtained during stimulation of the normal side using (i) a cold non-noxious stimulus identical to that applied to the painful side, and (ii) an electrical high-frequency stimulus at painful ranges. Statistical analysis disclosed two abnormal patterns of rCBF change during allodynia. First, there is a quantitative change whereby the blood flow response was out of proportion with the actual intensity of the stimulus, i.e. the pattern of activation by innocuous rubbing of the skin was in our patients identical to that previously reported in response to painful stimuli in normal subjects. This pattern concerned primarily the contralateral thalamus in its lateral half and the primary and somatosensory areas, as well as inferior parietal [Brodmann area (BA) 39/40], anterior insular (BA 6) and medial prefrontal (BA 10) cortices. Thalamic over-activity may reflect abnormal transduction and amplification of sensory inputs after spinothalamic deafferentation. This might be responsible for both increased rCBF in multiple cortical targets and the perceived shift of stimulus intensity from innocuous to painful ranges. The second abnormality associated with allodynic sensation was qualitative. It concerned exclusively the contralateral cingulate gyrus, which did not exhibit the usual pain-related rCBF increase reported in normal subjects. This abnormal cingulate response may account for the peculiar response of lateral medullary infarct patients to allodynic pain, which is not simply perceived as an exaggerated pain sensation, but as a new, strange and extremely unpleasant feeling, not previously experienced by the patients.