The key-question, when dealing with preemptive analgesia, its to know whether an analgesic intervention coming before surgery is as efficient, more efficient or less efficient than the same intervention following surgery. Surgical tissular damaging leads to a dual phenomenon of peripheral and central sensitization. The result is a state of neuronal hyperexcitability, so-called "wind-up phenomenon", which could partially explain postoperative painful states. Peripheral mechanisms involve many factors, especially prostaglandins that could be blocked by NSAIDs. Central mechanisms and neuroplasticity are analyzed, insisting on inter and intracellular biochemical events. The role of excitatory amino-acid is explained, especially of glutamic acid and the NMDA (N-methyl-D-aspartate) receptor at the spinal level.