Sensitization - Neural Substrates of Sensitization

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 has been proposed as a potential mechanism underlying memory and learning in the human 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 an 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 are 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.