Sensitization is a non-associative
learning
Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...
process in which repeated administration of a
stimulus
A stimulus is something that causes a physiological response. It may refer to:
*Stimulation
**Stimulus (physiology), something external that influences an activity
**Stimulus (psychology), a concept in behaviorism and perception
*Stimulus (economi ...
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
Eric Richard Kandel (; born Erich Richard Kandel, November 7, 1929) is an Austrian-born American medical doctor who specialized in psychiatry, a neuroscientist and a professor of biochemistry and biophysics at the College of Physicians and Surge ...
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
''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.
These benthic herbivorous creatures can become rather large compared with most ...
''. 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
[Squire LR, Kandel ER (1999). ''Memory: From Mind to Molecules.'' New York: Scientific American Library; New York: W.H. Freeman. .]). In 2000, Eric Kandel was awarded the
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for his research in neuronal learning processes.
Neural substrates
The neural basis of
behavioral sensitization
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use of ...
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
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
causes strengthening of
synaptic signal
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...
s, a process known as
long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
or LTP.
LTP of
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...
s is a potential mechanism underlying memory and learning in the brain.
* In "
kindling
Kindling is material for firelighting
Kindling may also refer to:
* ''Kindling'' (album), a 1973 album by Gene Parsons
* ''Kindling'' (film), a 1915 film by Cecil B. DeMille
* ''Kindling'' (Mick Farren novel)
* ''Ruined City'' (novel) or ''Ki ...
", repeated stimulation of hippocampal or
amygdaloid neurons in the
limbic system
The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...
eventually leads to
seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s 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
Temporal lobe epilepsy (TLE) is a chronic disorder of the nervous system which is characterized by recurrent, unprovoked focal seizures that originate in the temporal lobe of the brain and last about one or two minutes. TLE is the most common f ...
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 neuron
A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...
s in the
dorsal horns of the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
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
Reverse tolerance or drug sensitization is a pharmacological phenomenon describing subjects' increased reaction (positive or negative) to a drug following its repeated use. Not all drugs are subject to reverse tolerance.
This is the opposite of d ...
occurs in
drug addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use of ...
, and is defined as an increased effect of drug following repeated doses (the opposite of
drug tolerance
Drug tolerance or drug insensitivity is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further ...
). Such sensitization involves changes in brain
mesolimbic
The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
transmission, as well as a protein 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.
Cross-sensitization
Cross-sensitization is a phenomenon in which sensitization to a stimulus is generalized to a related stimulus, resulting in the amplification of a particular response to both the original stimulus and the related stimulus.
For example, cross-sensitization to the neural and behavioral effects of
addictive drug
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
s are well characterized, such as sensitization to the locomotor response of a stimulant resulting in cross-sensitization to the motor-activating effects of other stimulants. Similarly,
reward sensitization
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use of ...
to a particular addictive drug often results in
reward cross-sensitization
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use of ...
, which entails sensitization to the
rewarding property of other addictive drugs in the same
drug class
A drug class is a set of medications and other compounds that have a similar chemical structures, the same mechanism of action (i.e. binding to the same biological target), a related mode of action, and/or are used to treat the same disease.
In ...
or even certain
natural reward
Behavioral addiction is a form of addiction that involves a compulsion to engage in a rewarding non- substance-related behavior – sometimes called a natural reward – despite any negative consequences to the person's physical, mental, social ...
s.
In animals, ''cross-sensitization'' has been established between the consumption of many different types of
drugs of abuse
Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...
– in line with the
gateway drug theory
The gateway drug effect (alternatively, stepping-stone theory, escalation hypothesis, or progression hypothesis) is a comprehensive catchphrase for the often observed effect that the use of a psychoactive substance is coupled to an increased probab ...
– and also between
sugar
Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
consumption and the
self-administration
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
In animal experimentati ...
of drugs of abuse.
As a causal factor in pathology
Sensitization has been implied as a causal or maintaining mechanism in a wide range of apparently unrelated pathologies including
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
, allergies, asthma,
overactive bladder
Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. If there is loss ...
and some medically unexplained syndromes such as
fibromyalgia
Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...
and
multiple chemical sensitivity
Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is an unrecognized and controversial diagnosis characterized by chronic symptoms attributed to exposure to low levels of commonly used chemicals. Symp ...
. Sensitization may also contribute to psychological disorders such as
post-traumatic stress disorder
Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...
,
panic anxiety
Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
and
mood disorder
A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
s.
See also
*
Long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
*
Multiple chemical sensitivity
Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is an unrecognized and controversial diagnosis characterized by chronic symptoms attributed to exposure to low levels of commonly used chemicals. Symp ...
*
Neuroplasticity
Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of Neural circuit, neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that diffe ...
*
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuit ...
References
{{Learning
Behaviorism
Learning