Sensitization

eric kandel by Joseph Adolphe

Sensitization [sen-si-tuh-zey-shuhn] is an example of non-associative learning (learning involving exposure to a single event) in which the progressive amplification of a response follows repeated administrations of a stimulus. An everyday example of this mechanism is a warm sensation followed by pain caused by constantly rubbing an arm. The pain is the result of the progressively amplified response of the nerve endings.

Sensitization is thought to underlie both adaptive as well as maladaptive learning processes in the organism. Sensitization refers to the process by which a cellular receptor becomes more likely to respond to a stimulus (more efficient). There are a several of different types of sensitization: long-term potentiation, kindling, central sensitization, and drug  sensitization.

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 has been proposed as a potential mechanism underlying memory and learning in the human brain. ‘Kindling’ refers to repeated stimulation of hippocampal or amygdaloid neurons in the limbic system (paleomammalian brain) and eventually leads to seizures in laboratory animals. Having been sensitized, very little stimulation is required to produce the 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.

A third type is central sensitization, where 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. Drug sensitization occurs in drug addiction, and is defined as an increased effect of drug following repeated doses (the opposite of drug tolerance). Addiction may also be related to increased (sensitized) drug craving when environmental stimuli associated with drug taking, or drug cues, are encountered. This process may contribute to the risk for relapse in addicts attempting to quit. Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a molecule inside mesolimbic neurons called delta FosB. The mesolimbic pathway is one of the dopaminergic pathways in the brain. These various types indicate that sensitization may underlie both pathological and adaptive functions in the organism.

Sensitization has been implied as a causal or maintaining mechanism in a wide range of apparently unrelated pathologies including substance abuse and dependence, allergies, asthma, and some medically unexplained syndromes such as fibromyalgia and multiple chemical sensitivity. Sensitization has also been suggested in relation to psychological disorders such as post-traumatic stress disorder, panic anxiety, and mood disorders.

Eric Kandel was one of the first to study the neural basis of sensitization based on his experiments observing gill withdrawal of seaslugs in the 1960s and 1970s. Kandel and his colleagues showed that after habituation from siphon touching (gill withdrawal response weakened), applying a paired noxious electrical stimulus to the tail and a touch to the siphon, gill withdrawal was once again noted. After this sensitization, applying a light touch to the siphon, absent of noxious stimulus to the tail, produced a strong gill withdrawal response. When tested several days after the initial trials, this response was still manifest. In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes.

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