Sensitization is a non-associative learning process in which repeated administrations 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.
Neural substrates of sensitization
|• addiction – a state characterized by compulsive engagement in rewarding stimuli despite adverse consequences|
|• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them|
|• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached|
|• addictive drug – a drug that is both rewarding and reinforcing|
|• addictive behavior – a behavior that is both rewarding and reinforcing|
|• sensitization – an amplified response to a stimulus resulting from repeated exposure to it|
|• drug tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose|
|• drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose|
|• dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)|
|• physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)|
|• psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)|
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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 pain threshold will change and result in a stronger pain response. Researchers believe that there are parallels that can be drawn between these animal trials and persistent pain in people. For example, after a back surgery that removed a herniated disc from causing a pinched nerve, the patient may still continue to “feel” pain. Also, newborns who are circumcised without anesthesia have shown tendencies to react more greatly to future injections, vaccinations, and other similar procedures. The responses of these children are an increase in crying and a greater hemodynamic response (tachycardia and tachypnea).
- Drug sensitization occurs in drug addiction, and is defined as an increased effect of drug following repeated doses (the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a molecule inside mesolimbic neurons called delta FosB. An associative process may contribute to addiction, for environmental stimuli associated with drug taking may increase craving. This process may increase the risk for relapse in addicts attempting to quit.
- Allergic Sensitization – There is an acute response (early stages) and a late-phase response (later stages). In the early stages, the Antigen-Presenting Cell causes a response in a TH2 lymphocyte which produce the cytokine interleukin-4 (IL-4). The TH2 lymphocytes interact with B cells and together they produce IgE. IgE circulates around and binds to receptors of cells leading to an acute inflammatory response. In this case, sensitization is commonly referring to commencement of allergic responses. Allergic sensitization development varies with age, with younger children at the greatest risk of developing allergic sensitization. There are a variety of tests to diagnose allergic conditions. Tests that are commonly used place potential allergens on the skin of the patient and looking for a reaction to look for an allergen-specific IgE (Immunoglobulin E). They have shown that IgE levels are at their greatest before 10 years of age and fall vastly until one reaches 30. There is a school of thought that believes that there are different genetic loci for different ethnicities for the same inflammatory disease. By this thought, asthma has different chromosomal locations in people of European, Hispanic, Asian, and African descent.
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 the seaslug Aplysia 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 for his research in neuronal learning processes.
Possible correlation with animal cognition
It is important to note the possible correlation between sensitization and animal cognition. The continual stimulation of the rat hippocampus results in LTP. This is a proposed mechanism of memory formation. Sensitization is an increased response to a stimulus that results in LTP and it is plausible that nonhuman animals, in addition to humans, exhibit cognitive ability in the form of memory development.  More research is needed to prove or disprove the connection between these two phenomena.
- Long-term potentiation
- Synaptic plasticity
- Multiple Chemical Sensitivity
- Animal cognition
- Plant cognition
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