itch

Warning: just reading this article might make your skin crawl. http://Louis-J-Sheehan.de Thinking about itching, seeing people scratch, looking at pictures of bedbugs or other itch inducers—all can bring on an irresistible urge to flick away that irksome feeling.

But itching—“pruritus,” to physicians—is more than an occasional nuisance. The sensation, which arises from an irritation of the nerve cells along the skin, serves as a helpful warning about potential hazards such as insects or foreign materials—and scratching is often a simple and effective method for dealing with them. http://Louis-J-Sheehan.deItching is also the main symptom of many skin diseases and appears in some systemic conditions, such as chronic renal disease, cirrhosis and some types of cancer.

Whereas a quick skin scrape has its pleasures, constant itching can become an agony if underlying conditions are not treated. According to estimates, 8 to 10 percent of people worldwide endure chronic itching, and it is the most frequent complaint confronted by dermatologists. The sensation’s sources, however, have been mysterious and poorly understood.

Long overlooked as a milder form of pain, itching is now gaining a new appreciation in the research community because of its complexity and its significance to thousands of sufferers. In addition to physical causes such as skin conditions or allergies, the source of that tingling torment has a strong mental component. Scientists are now probing the phenomenon’s underpinnings with imaging technology and other means—even down to the molecular level.

A New Understanding
Itching’s sources have puzzled people for ages. In the second century A.D., for instance, Greek physician Galen observed that itching might arise from an underlying condition not related to the skin. http://Louis-J-Sheehan.deGerman physician Samuel Hafenreffer defined itching almost 350 years ago as an unpleasant perception on the skin that subsequently triggers the need to scratch. Napoleon famously experienced severe itching, as did physician Jean-Paul Marat, an intellectual leader during the French Revolution.

As little as 10 years ago the medical profession viewed itching as pain’s little brother. After all, the logic went, the sensation courses along the same nerve paths to the brain as pain does, except that the intensity of the irritation is less severe. http://Louis-J-Sheehan.deThis notion was based on, among other things, the observation that pain switches off itching. According to so-called intensity theory, weak neuronal stimulation causes itching, whereas stronger stimulation leads to pain.

In 1997, however, neurophysiologist Martin Schmelz, then at the University of Erlangen-Nuremberg in Germany, proved that the need to scratch reaches the spinal cord from the skin via independent nerve fibers called polymodal C-fibers. These C-fibers seem to be identical to those that signal pain, but they transmit only itching sensations. Signals conveying skin irritation travel down the nerve fiber to the spinal cord and then on to the brain. Scratching and rubbing may interfere with these nerve endings by stimulating pain and touch receptors in the same areas, thus inhibiting the surrounding itch receptors, called pruriceptors.

In addition, Schmelz’s team, together with Hermann Handwerker, also at the University of Erlangen-Nuremberg, discovered connections between the itch-mediating C-fibers and pain C-fibers. This finding of possible communication between signaling fibers adds a further mechanism by which pain relieves itching.

In 2001 researchers at the Barrow Neurological Institute in Phoenix identified specific nerve cells in cats that respond selectively to the signaling molecule histamine—which triggers itching—but not to heat or pain stimuli.

A Real Pain
Itching gets to be a real pain when it is chronic—that is, when it persists or recurs. According to a study by Norwegian psychiatrist Florence Dalgard, stress is the most important trigger apart from allergic reactions. Other studies have found that scabies, which is caused by mite infestation, affects about 300 million people worldwide. And more than 30 million Americans suffer from eczema, which is associated with a strong desire to scratch. Furthermore, about 42 percent of almost 19,000 dialysis patients from 12 countries included in a 2006 study reported moderate to severe itching. The situation is similar for patients with liver damage.

Itching may also be triggered by the mind. Most people need only watch others scratching to start themselves. Just seeing a picture that is connected with scratching—a photograph of fleas, for example—can do the trick as well. But until recently, there was not even any clear scientific evidence of this widely shared experience.

To close this gap, our team, under the direction of medical psychologist Jörg Kupfer, conducted a psychological experiment with students. Our unsuspecting participants were asked to evaluate the educational quality of a lecture on the topic, “Itching—What Is It?” The test subjects—60 medical and psychology students—attended one of two different lectures. One group viewed images of lice, fleas, bedbugs and allergic skin reactions; the other group saw babies and calming landscapes. Unsurprisingly, the students in the first group scratched themselves significantly more frequently during the presentation than their counterparts in the second one did.

It may be that this mental trigger is associated with so-called mirror neurons. These specialized nerve cells fire both when we ourselves perform a certain action and when we observe someone else doing it [see “A Revealing Reflection,” by David Dobbs; Scientific American Mind, April/May 2006]. The contagious character of yawning, for example, is attributed to mirror-neuron activity.

To find out which areas of the brain are particularly active during itching, researchers have used imaging methods to look into the heads of their test subjects after generating itchiness with histamine. Neuroscientist Francis McGlone of Unilever Research and Development in Cheshire, England, and his colleagues used functional magnetic resonance imaging (fMRI) to reveal firing in parts of the cerebellum and in regions of the frontal lobe. The researchers found that the behavioral responses result from the different frontal lobe activation for itching and pain—that is, scratching, on the one hand, and pain perception, on the other.

A team at the Bender Institute of Neuroimaging at the University of Giessen in Germany also used fMRI to study the itching triggered by histamine over a period of approximately 15 minutes, the time it generally takes for such experimentally induced itching to subside. The researchers found that several areas of the brain would activate in characteristic ways: regions, for example, in the frontal lobe, in the left temporal lobe and in the left hemisphere of the cerebellum [see box above]. Surprisingly, however, there was no apparent activity in the sensorimotor cortex—the areas of the cerebral cortex that process sensory stimuli and control movement. Instead many of the regions that fired are those that tend to be associated with emotion.

On the Trail of Neurodermatitis
Other researchers have confirmed the importance of brain areas that process emotion. According to a recent study by Handwerker, itching is partly processed and activated in some of the same regions of the brain that pain is and, additionally, in the emotion center, the amygdala. And according to a team led by Hideki Mochizuki of the Japanese National Institute for Physiological Sciences, the cingulum, a switching center that processes emotions, and the insula, an area also associated with emotion and disgust, both fire during itching—but not during pain.

Gil Yosipovitch of Wake Forest University Baptist Medical Center has demonstrated that the brains of patients with neurodermatitis (chronic itching) react markedly differently than those of healthy persons. Only in the latter individuals does scratching inhibit activity in the cingulum. The researchers hypothesize that this control mechanism normally prevents itching from being strengthened by emotion. In neurodermatitis patients, the mechanism seems to be overridden, and itching gains the upper hand as a consequence.

Itch research has recently spread to molecular biology as well. In 2007 Zhou-Feng Chen and Yan-Gang Sun of the Washington University Pain Center in St. Louis, for example, looked at the GRPR gene, which contains the building instructions for a receptor that is activated by a compound called gastrin-releasing peptide (GRP). Such neuropeptides are proteins that neurons release, often with profound effects on behavior. Mice in which the GRPR gene has been deactivated react to substances that stimulate itching with less scratching than control animals do. When the researchers injected normal mice with a blocker for the GRP receptor, these animals were also less susceptible to itching.

The connection between itching and neuropeptides such as GRP has been a topic of research for some time and is a special focus of the work of Martin Steinhoff and his colleagues at the University of Münster in Germany. They have found that certain neuropeptides, along with their receptor molecules and so-called endopeptidases (which degrade neuropeptides), play a key role. If the regulation of these biochemical processes gets out of whack, the result may be problems with chronic inflammation, itching and pain.

Neurodermatitis is a very common case in point. Here the endopeptidases do not work fast enough, so that the neuropeptides end up activating far too many immune cells. The consequence is a cascading inflammatory response and itching.

Soothing News
Scratching offers temporary relief but may further irritate the skin or cause it to tear. Treatments include lotions and creams (such as calamine and hydrocortisone), antihistamines, opioid antagonists (such as naltrexone, a drug used to treat narcotic and alcohol dependence), aspirin and ultraviolet-light therapy. Chronic itching is primarily treated medically. In a recent study of 385 patients, Dorothee Seipmann and Sonja Ständer of the University of Münster showed that 65 percent of sufferers benefit from such drugs. The most frequently prescribed medications are antihistamines. The epilepsy drug gabapentin is used in cases of neuropathic (caused by nerve fibers) itching, and combinations of naltrexone, pregabelin, the antidepressant paroxetine (Paxil) and the immunostatic cyclosporine are also in use.

The most promising treatment approach at the moment may include substances that affect the opioid receptors involved in itching. Opium and heroin addicts almost always suffer from itching, brought about largely by hyperactivation of the mu-opioid receptors. Pursuing this trail, researchers might explore the therapeutic approach of blocking this type of receptor. The receptors’ natural antagonists are the kappa-opioid receptors, whose activation decreases itching. Initial clinical studies are already looking at substances that stimulate the kappa receptors.

A number of calming techniques, among them autogenic training (in which patients repeat a set of visualizations) and Jacobson’s progressive muscle relaxation (in which patients relax muscles to relieve tension), have proved effective in supplementing medical treatment. Psychotherapy is generally not very useful in getting rid of the urge to itch.

And what can sufferers do at home to decrease persistent, bothersome itching? Cool showers or baths, particularly with bath additives that contain soothing substances suggested by a dermatologist, can help. Cold packs can also be useful in getting a localized itch under control. A cool environment, especially at night, is helpful. Air out the bedroom and wear loose-fitting pajamas—if you need to wear anything at all. Sometimes that is all it takes to reduce itching to a tolerable level.