Central pain syndrome (CPS) is a debilitating and chronic pain condition that results from a lesion or dysfunction in the CNS. The pathophysiological mechanisms underlying CPS are poorly understood. We recently demonstrated that CPS is associated with suppressed inputs from the inhibitory nucleus zona incerta to the posterior thalamus (PO). As a consequence, activity in PO is abnormally increased in CPS. Because the perception of pain requires activity in the cerebral cortex, CPS must also involve abnormal cortical activity. Here we test the hypothesis that CPS is associated with increased activity in the primary somatosensory cortex (SI), a major projection target of PO that plays an important role in processing sensory-discriminative aspects of pain. We recorded activity of single units in SI in rats with CPS resulting from spinal cord lesions. Consistent with our hypothesis, SI neurons recorded from lesioned rats exhibited significantly higher spontaneous firing rates and greater responses evoked by innocuous and noxious mechanical stimulation of the hindpaw compared with control rats. Neurons from lesioned rats also showed a greater tendency than controls to fire bursts of action potentials in response to noxious stimuli. Thus, the excruciatingly painful symptoms of CPS may result, at least in part, from abnormally increased activity in SI.