Over the last few years, the mechanisms of pain due to peripheral nerve injury have been the subject of extensive clinical and fundamental investigation. Several types of peripheral mechanisms have been described in animal models of peripheral nerve injury. Abnormal (ectopic) neuronal activity has been reported in primary afferents and in the dorsal root ganglion, and appears related to dysregulation of the synthesis and/or the functioning of sodium channels (notably the tetrodotoxin-resistant channel). Fiber interactions (ephaptic or cross-excitation), nociceptor sensitization and sympathetic sensory coupling may also be involved in some cases. Peripheral nerve lesions can also induce central changes; this has essentially been investigated at the spinal cord level in animals. Three major types of modifications could induce a pathologic activation of central nociceptive neurons: modification of the modulatory controls of the transmission of nociceptive messages; anatomic reorganization (neuroplasticity) of the central nociceptive neurons, and thus their pathologic activation; and central sensitization (hyperexcitability) of nociceptive neurons to produce modifications of their electrophysiologic properties. Central sensitization probably depends critically on intracellular changes induced by the activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids released by primary afferents. Due to the multiplicity of mechanisms, it is unlikely that neuropathic pain corresponds to a unique entity. Each of the painful symptoms may correspond to distinct mechanisms and thus respond to specific treatments.