Sensitization
Encyclopedia
Sensitization is an example of non-associative learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...

 in which the progressive amplification of a response follows repeated administrations of a stimulus
Stimulation
Stimulation is the action of various agents on nerves, muscles, or a sensory end organ, by which activity is evoked; especially, the nervous impulse produced by various agents on nerves, or a sensory end organ, by which the part connected with the nerve is thrown into a state of activity.The word...

. An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm continuously. After a while, this stimulation will create a warm sensation that will eventually turn painful. The pain is the result of the progressively amplified synaptic
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

 response of the peripheral nerves warning the person that the stimulation is harmful. Sensitization is thought to underlie both adaptive as well as maladaptive learning processes in the organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...

.

Types of sensitization

Sensitization refers to the process by which a cellular receptor becomes more likely to respond to a stimulus (more efficient). There are a couple of different types of sensitization:
  • Electrical or chemical stimulation of the rat hippocampus
    Hippocampus
    The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

     causes strengthening of synaptic signals, a process known as long-term potentiation
    Long-term potentiation
    In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...

     or LTP. LTP of AMPA receptor
    AMPA receptor
    The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...

    s has been proposed as a potential mechanism underlying memory and learning in the human brain.
  • A different type of sensitization is that of kindling
    Kindling
    Kindling is a term to describe small pieces of wood and twigs used to start a fire.Kindling may also refer to:* Kindling, a 1915 film directed by Cecil B...

    , where repeated stimulation of hippocampal or amygdaloid
    Amygdala
    The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

     neurons in the limbic system
    Limbic system
    The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...

     eventually leads to seizure
    Seizure
    An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

    s 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
    Temporal lobe epilepsy
    Temporal lobe epilepsy a.k.a. Psychomotor epilepsy, is a form of focal epilepsy, a chronic neurological condition characterized by recurrent seizures. Over 40 types of epilepsies are known. They fall into two main categories: partial-onset epilepsies and generalized-onset epilepsies...

     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 affect 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
    Spinal cord
    The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

     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
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     transmission, as well as a molecule inside mesolimbic neurons called delta FosB.


These various types indicate that sensitization may underlie both pathological and adaptive functions in the organism.

Etiology

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
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

 and multiple chemical sensitivity
Multiple chemical sensitivity
Multiple chemical sensitivity is a chronic medical condition characterized by symptoms the affected person attributes to exposure to low levels of chemicals. Commonly suspected substances include smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products and paints...

. Sensitization has also been suggested in relation to psychological disorders such as post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

, panic anxiety and mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s.

History

Eric Kandel was one of the first to study the neural basis of sensitization based on his experiments observing gill withdrawal of the seaslug Aplysia
Aplysia
Aplysia is a genus of medium-sized to extremely large sea slugs, specifically sea hares, which are one clade of large sea slugs, marine gastropod mollusks. The general description of sea hares can be found in the article on the superfamily Aplysioidea....

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, Aplysia produced a strong gill withdrawal response. When tested several days after the initial trials, this response was still manifest (After Squire and Kandel, 1999). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

for his research in neuronal learning processes.
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