The IASP defines neuropathic pain as pain that is caused by a lesion or disease of the somatosensory system. The pathophysiology involves a complex and redundant interplay of neural generators, circuits, and mediators. Neuroanatomical changes consist of both peripheral and central adaptive and maladaptive mechanisms. The adaptive processes include changes in pro-nociceptive and anti-nociceptive systems.
In normal sensory experience, a noxious stimulus applied to nociceptive sensory endings is transmitted to the brain. Inflammation can lead to nociceptive endings becoming hypersensitive causing inflammatory pain. When an injury or disease affects the peripheral nerves (neuropathy), sensory ganglia (ganglionopathy), or sensory roots (radiculopathy), then pain signals can occur in areas ectopically away from the sensory ending. Abnormal impulse discharge can then lead to neuropathic pain. A range of inciting events can lead to ectopic impulse discharge, such as trauma, nerve entrapment, infection, inflammatory, metabolic disturbance, malnutrition, vascular disease, toxins, radiation, and genetic. Most commonly ectopic impulse generation arises from the site of injury and the associated dorsal root ganglion. This abnormal impulse discharge can not only drive pain sensation (spontaneous or evoked), but also induce and maintain central nervous system pain amplification processes.