Referred itch or mitempfindung is the phenomenon in which a stimulus applied in one region of the body is felt as an itch or irritation in a different part of the body. The syndrome is relatively harmless, though it can be irritating, and healthy individuals can express symptoms. Stimuli range from a firm pressure applied to the skin – a scratch – to irritation or pulling on a hair follicle on the skin.
[Schott GD. "Distant referral of cutaneous sensation (Mitempfindung). Observations on its normal and pathological occurrence." Brain. 1988 Oct., Vol. 111, Issue 5: 1187-1198.] The referred sensation itself should not be painful; it is more of an irritating prickle leading to the compulsion to scratch the area. The stimulus and referred itch are
ipsilateral (the stimulus and the referred itch occur on the same side of the body). Also, because scratching or putting pressure on the referred itch does not cause the stimulus area to itch, the relationship between the stimulus and the referred itch is unidirectional.
The itching sensation is spontaneous and can cease with continued stimulation.
There are two types of referred itch: normal and acquired (pathological). Normal mitempfindung is usually detected in early childhood and persists for the majority, if not the rest, of the individual's life. Acquired or pathological mitempfindung is the effect of damage to the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
and only lasts for a short period of time.
Symptoms are variable among affected individuals, but it is widely accepted that the soles of the feet, palms, and the face are never affected by mitempfindung. There is no evidence of genetic influence on referred itch.
There is a published study, however, that mentions an affected man whose children were also affected. Much is still unknown about the physiological mechanisms of the phenomenon, and no single theory is accepted.
Research and information regarding mitempfindung is limited and dated. Most research on the topic was conducted in the late 19th century, and the most recent publications occurred in the late 1970s. A handful of studies were done in the early 1990s, but further data must be collected and interpreted before a thorough understanding of mitempfindung is reached.
Signs and symptoms
Location of original itch and referred itch
The location of the reference point for each individual that experiences referred itch is well conserved and specific to each person, in that a certain location will elicit the phenomenon repeatedly for a given person while itches elsewhere may not. However, frequent and repetitive stimulation of the same original itch location can weaken the phenomenon, making the referred itch increasingly more discrete with each repeated trial.
There is also no evidence of a relationship between the site of the original stimulus and that of the referred itch.
Though the location of the referred itch may remain fairly constant and precise for a particular stimulus location on a single individual, there is no substantial evidence linking any two locations in a definite origin/referred location relationship. Thus, referral patterns are extremely variable and offer little to no indication of where a referred itch will occur if the location of the original itch is known. The phenomenon is unidirectional.
Consequently, scratching an itch in a location that has previously served as the point of a referred itch does not induce an itch in the person's typical origination site.
Synesthesia and mitempfindung
Mitempfindung has been thought to be related to
synesthesia
Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People who re ...
in some individuals, specifically digit-color
synesthesia
Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People who re ...
.
Digit-color synesthesia is a phenomenon in which affected individuals associate individual numbers with certain colors; individuals have been said to "count in colors."
Both synesthesia and mitempfindung develop in early childhood and are highly variable among individuals.
Furthermore, synesthesia and mitempfindung are both unidirectional. A scratch on the trigger zone creates a referred sensation in a distant body part but not vice versa. Likewise, in synesthesia, a person's association of a number with a color does not mean that that color aways evokes that number for them.
Normal and pathological referred itch
Referred itch is the class of referred sensation that focuses on the situation in which an itch in one place on the body simultaneously triggers an itch in a different location. Other examples of referred sensation include sensations of temperature, pain, and pressure.
Referred itch is commonly observed in completely healthy individuals and can often go unnoticed depending upon the particular person's self-awareness of their itches and the causes of those itches. The ephemeral nature of referred itch and its restriction to a very small area on one's body (the itch is precisely located, it does not induce widespread itching) make it difficult to document or even notice.
The majority of the cases of referred itch studied by experimenters occur in healthy individuals. Furthermore, referred itch itself does not confer any adverse effects on the health of those experiencing it. With the exception of the annoyance of feeling multiple itches and a potentially minuscule feeling of pain, it is an innocuous condition. The cause of referred itch in healthy individuals is still not known for certain, but there are a multiple recorded cases of referred itch being triggered by certain pathological stimuli.
Two men developed temporary referred sensation following
shingles
Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
. Here, the referred sensation occurred in the areas previously affected by the shingles.
Another man who had
hyperpathia and reduced nerve functioning later experienced referred itch in conjunction with his pathology.
This evidence suggests that although referred itch occurs spontaneously in healthy individuals, certain pathologies make it possible to acquire the condition, even if only temporarily.
Causes
Itch (pruritus) has many causes. Allergies and inflammatory skin disease all produce itch as a symptom. Pathophysiologically, the sensation of the itch is poorly understood. Nevertheless, there are many known inducers of itch.
Histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
is widely known as an inducer of the itch sensation. Other substances known to induce itch are
substance P,
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s, and
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s.
Temperature also has an effect. It is conventional opinion that applied cold temperature inhibits itch by inhibiting
C-fiber
Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A a ...
activity. However, studies have also described paradoxical phenomena associated with temperature and itch, where applied short-term moderate cold temperature stimulus enhanced the itch. Such a phenomenon might be explained by "paradoxical heat", which is when one has the perception of heat when, in fact, the skin is innocuously cooled. Thus, the exact effect of temperature on itch remains unclear, with different levels of heat and cold proven to both enhance and inhibit itch.
Alcohol is known to have close interactions with histamine release. Alcohol both stimulates the release of histamine from mast cells and inhibits its degradations by inhibiting
diamine oxidase. Though histamine is used by the body to mediate alcohol-induced gastric and intestinal damage as well as
alcohol flushing, it is possible that elevated levels of histamine might have a correlation with referred itch (or even itch in general).
Mechanisms
An
itch, also known as pruritus, is classified as a sensory stimulation to scratch a certain area of the skin. An itch can be a fleeting sensation, as with a random tickle or prick, or persistent, as with a rash such as
eczema or other skin irritant such as an
allergen. Itch has been demonstrated to be closely related to pain and to share many of its physiological mechanisms. The relationship between pain and itch is evident in the fact that itch sensations occur along a similar neurological and sensory pathway as sensations of pain, and the fact that individuals who are insensitive to pain are also insensitive to itch.
Itch is induced by mechanical, chemical, thermal, or electrical stimuli of sensory receptors in the
peripheral nervous system, or by psychological prompts. The receptors that are responsible for the sensation of itch caused by environmental stimuli are found within the
upper layers of the skin. Once stimulated, usually by histamine within the body, a signal is sent through the peripheral nervous system to the brain (
thalamus), where the information is processed and the command for the bodily response is issued.
Itch can also originate as a result of damage to the nervous system (central or peripheral) or in response to the presence of excess
opioids.
Because of the scarcity of research available on mitempfindung, there is no widely accepted theory on how the referral of sensation is manifested. There are, however, a wide range of hypotheses which carry traction within the scientific community.
One proposed mechanism implicates the
nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
and its branches. At the cellular level, this hypothesis postulates that abnormal branching of neurons occurs during
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
.
During development, the branch of an afferent article may travel unusually far in the nervous system. Thus, in an individual with a fully developed
nervous system, the stimulus at the end of one branch may be interpreted as coming from a point of ending in another, distant, part of the body. Again, research has not been done to prove this hypothesis as valid or invalid.
There is an untested hypothesis that claims that referred itch uses the
spinocervical tract pathway.
The cells in this tract lie in the
dorsal horn of the
spinal cord, and its
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action ...
s run in the
ipsilateral and dorsolateral quadrant, which is consistent with observations that stimuli in the trigger points are ipsilateral to the sites of referred sensations. These axons project to the
thalamus and
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal ( alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
, suggesting that the thalamus is involved in the phenomenon. The cells in this tract are also excited by mechanical stimuli, lending support that this pathway can explain the mechanism of referred itch. Central neuronal damage to this area – either direct or secondary to peripheral nerve damage – makes it an area of focal
hyperexcitability or reduced inhibition. This hypothesis has been found to be unlikely because there would be an expected progression of itches (i.e., from legs to trunk, and from trunk to neck).
However, there is no symmetrical distribution found between trigger zones and sites of referred sensation.
There is great support behind the idea of the thalamus affecting mitempfindung.
Because of the arrangement of sensory regions in the thalamus, there may be a spread of excitation in this brain region. Studies have shown that the thalamic region dedicated to the trunk is found between the regions supporting sensation from the arms and legs. This supports the finding that trigger zones in the chest area lead to referred sensation in the legs. And since the thalamic region for the face lies in a separate area called the
arcuate nucleus
The arcuate nucleus of the hypothalamus (also known as ARH, ARC, or infundibular nucleus) is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes severa ...
, this explains why the face remains unaffected by referred itch.
Some spread in association within the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...
may also explain the large distances between trigger points and referred sensation sites.
In the precentral area where the
homunculus
A homunculus ( , , ; "little person") is a representation of a small human being, originally depicted as small statues made out of clay. Popularized in sixteenth-century alchemy and nineteenth-century fiction, it has historically referred to the ...
rests, it is known that hand and shoulder areas overlap the trunk area. And the area of the thumb overlaps that of the upper part of the tongue. There is a published case in which stimulation in the thumb led to a referred sensation in the upper part of the tongue.
Management
The origin of referred itch is unknown, whether it be
neuropathic
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
(originating in the brain), pruritoceptic (originating at the skin), or disease related, so treatment for it specifically still remains unclear. Nevertheless, treatment for different kinds of itch, some of which may be applicable to referred itch, are available. Note that people with this symptom should seek medical care and consult appropriate medications with a doctor.
Aspirin taken orally has minimal effect on itch.
Therapeutic options for itch that originates in the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
are limited, and need further confirmation, but are in general based on the counteracting interaction between itch and pain via the spine.
[Department of Dermatology, Wake forest, et al. 2003 Itch] Treatments of low dosage
lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, li ...
and
gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diab ...
might be effective in relieving itch that is thought to originate in the central nervous system.
Epidemiology
The prevalence of mitempfindung is difficult to determine exactly, because many individuals would not be aware of having referred itch until the phenomenon is explained to them. Consequently, variability exists within the scientific literature as to the actual prevalence of referred itch in humans.
Mittelmann (1920) has reported that 8 out of 9 people questioned experienced referred sensations. In 1973, Sterling reported that about half of 20 healthy individuals questioned had mitempfindung.
The variability and heterogeneous characteristic of mitempfindung among individuals makes it difficult to determine a precise set of identifying symptoms of the disease, or a set of
risk factor
In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often us ...
s. Nevertheless, mitempfindung is thought to be extremely common.
History
The term mitempfindungen (literally "associated sensations") was first used in 1844 by the German scientist Johannes Müller. "Referred itch" was only used after 1884, in context to the research of Russian physiologist N. Kowalewsky. The phenomenon of referred itch was documented as early as 1733. Around that time, the English scientist
Stephen Hales
Stephen Hales (17 September 16774 January 1761) was an English clergyman who made major contributions to a range of scientific fields including botany, pneumatic chemistry and physiology. He was the first person to measure blood pressure. He a ...
observed that when an area of the body was scratched by the nails, an itching sensation could be triggered on a distant part of the body. He had called the phenomenon the many "Instances of the Sympathy of the Nerves."
[Hales S (1733) Statical Essays, Volume 2. London: W. Innys, R. Manby and T. Woodmward, pp. 59-60.] More extensive observations on the referral of sensation were documented by
Kowalewsky, who observed referred sensations on himself. Kowalewsky published his findings in 1884.
Current research
Although referred itch was first observed nearly 280 years ago, its cause and mechanism between stimulus and referred itch still remain vague and unproven. Up to this point, the most convincing evidence points toward the
thalamus,
sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...
, and chemical signals (like histamine) as the major aspects of our physiology responsible for the phenomenon, as explained above. Increasing knowledge of itching in general and its similarities with pain in the future could help to reveal some of what is unknown about referred itch, as could a better understanding of histamine and the
C-fibers' involvement with itch sensations. Without question, there is a need for further experimentation and study to be directed at referred itch, particularly as the body of evidence pertaining to it is scattered and often inconclusive.
References
Further reading
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External links
{{DEFAULTSORT:Referred Itch
Pruritic skin conditions