Limb denervation leads to reorganization of the representational zones of the somatosensory cortex. Using [11C](R)-PK11195, a sensitive in vivo marker of glial cell activation, and PET, we provide first evidence that limb denervation induces a trans-synaptic increase in [11C](R)-PK11195 binding in the human thalamus but not somatosensory cortex: these brain structures appeared morphologically normal on magnetic resonance imaging (MRI). The increased thalamic signal was detectable many years after nerve injury, indicating persistent reorganization of the thalamus. This glial activation, beyond the first-order projection area of the injured neurons, may reflect continually altered afferent activity. Our findings support the view that long-term rearrangement of cortical representational maps is significantly determined within the thalamus.