Both mechanical and biochemical factors are involved in the pathophysiology of nerve root compression. Chronic compression produces severe demyelination and fibrosis of the nerve root. Similar lesions can result from exposure to irritant substances released from the nucleus pulposus. Pain sensations arise from the peripheral nervous system as a result of structural radicular damage and sensitization. Structural nerve root changes (deafferentation, formation of ephapses or microneuromas) increase the sensitivity of the spinal nociceptive neurones. Algogenic substances are released that lower the activation threshold of nociceptors, producing peripheral sensitization. In the central nervous system, neuroplasticity and increased transmission of nociceptive signals in the spinal cord result in permanent excitation and sensitization of the spinal convergent neurones. The practical implications of these data are discussed.