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
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 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. Drug sensitization occurs in drug
addiction, and is defined as an increased effect of drug following
repeated doses. Such sensitization involves changes in brain mesolimbic
dopamine 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.
Allergic Sensitization – There is an acute response and a late-phase
response. In the early stages, the Antigen-Presenting Cell causes a
response in a TH2 lymphocyte which produce the cytokine interleukin-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.
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. Cause
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.
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 in the 1960s and 1970s. Kandel and his
colleagues showed that after habituation from siphon touching, 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. 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. See also
Long-term potentiation Synaptic plasticity
Neuroplasticity Multiple Chemical Sensitivity
Animal cognition Plant cognition
Practopoiesis References