Increasing evidence consistently indicates that cortical mechanisms play important roles in chronic pain and its emotional disorders. Central synapses, especially excitatory synapses, are undergoing long-term memory-like plastic changes after peripheral injury. These changes not only occur at the single synaptic level, but also take place at cortical and subcortical circuits. Consequently, neuronal responses to peripheral sensory stimuli, or even to sensory inputs triggered by normal physiological signals such as touch and movement, are significantly potentiated or increased. Such prolonged cortical excitation likely contributes to chronic pain and its related emotional changes. In this short review article, I will summarize recent progress using animal models and explore possible different mechanisms that may contribute to chronic pain in the brain.