Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of stimuli in addition to the one that is repeated. For example, repetition of a painful stimulus may make one more responsive to a loud noise. History Eric Kandel was one of the first to study the neural basis of sensitization, conducting experiments in the 1960s and 1970s on the gill withdrawal reflex of the seaslug Aplysia. Kandel and his colleagues first habituated the reflex, weakening the response by repeatedly touching the animal's siphon. They then paired noxious electrical stimulus to the tail with a touch to the siphon, causing the gill withdrawal response to reappear. After this sensitization, a light touch to the siphon alone produced a strong gill withdrawal response, and this sensitization effect lasted for several days. (After Squire and Kandel, 1999). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes. Neural substrates The neural basis of behavioral sensitization is often not known, but it typically seems to result from a cellular receptor becoming more likely to respond to a stimulus. Several examples of neural sensitization include: Electrical or chemical stimulation of the rat hippocampus causes strengthening of synaptic signals, a process known as long-term potentiation or LTP. LTP of AMPA receptors is a potential mechanism underlying memory and learning in the brain. In "kindling", repeated stimulation of hippocampal or amygdaloid neurons in the limbic system eventually leads to seizures in laboratory animals. After sensitization, very little stimulation may be required to produce seizures. Thus, kindling has been suggested as a model for temporal lobe epilepsy in humans, where stimulation of a repetitive type (flickering lights for instance) can cause epileptic seizures. Often, people suffering from temporal lobe epilepsy report symptoms of negative effects such as anxiety and depression that might result from limbic dysfunction. In "central sensitization", nociceptive neurons in the dorsal horns of the spinal cord become sensitized by peripheral tissue damage or inflammation. This type of sensitization has been suggested as a possible causal mechanism for chronic pain conditions. The changes of central sensitization occur after repeated trials to pain. Research from animals has consistently shown that when a trial is repeatedly exposed to a painful stimulus, the animal’s