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Creation Date: 30 Nov 2010 | Review Date: 30 Nov 2010

Itch: More Than Skin Deep

Itch is a sensation most of us rarely think about. We get an itch. We scratch. But severe, chronic itch can become debilitating and even life-threatening. Thanks to continuing brain research, scientists are developing a better understanding of the nerve pathways and genetic factors that underlie itch. This knowledge may help bring more effective treatments to people who live with itchy skin conditions. 

Studies show the chemical gastrin-releasing peptide (red), which is produced in the dorsal root ganglion (shown) and acts in the spinal cord, may be important in itch.
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Studies show the chemical gastrin-releasing peptide (red), which is produced in the dorsal root ganglion (shown) and acts in the spinal cord, may be important in itch.
Adapted by permission from Macmillan Publishers Ltd: Nature 448: 700–703, copyright 2007.

Scratching an itch is one of life’s simple pleasures. But, as scientists are discovering, it’s neurologically complex. Although an itch may be felt on the skin, long nerve fibers transmit that feeling from the skin to the spinal cord and brain. Our skin isn’t even necessary for us to “feel” an itch; just seeing images of “itchy” things — such as fleas, lice, bedbugs, or skin rashes — can make us start scratching.   

Scientists believe the sensation of itch — known medically as pruritus — may have developed to protect us from potential hazards such as disease-carrying insects. Scratching allows us to flick away a mosquito or flea before it can bite and leave its toxins. Itch is also a symptom of many skin disorders, such as psoriasis and eczema, as well as a complication of liver and kidney disease, and other illnesses. Most itches are nothing more than a temporary annoyance, but a chronic or severe itch can be disabling, causing an agonizingly relentless urge to scratch. Unfortunately, anti-itch therapies are not always effective and some people scratch themselves raw, even when asleep. 

New research is enabling scientists to solve many of the neurobiological mysteries of itch. For example, how is itch related to pain? To answer this and other questions, researchers are studying itch nerve pathways, including those in the central nervous system. Scientists have also identified several genes that may be related to itch. These discoveries are leading to: 

• The development of better treatments for people with chronic, debilitating itch

• Insight into how the brain processes sensory stimuli

Previously, observations of people who itch led researchers to associate itch with pain, as an itch-relieving scratch can become painful if done to excess.  But, pain medications such as morphine often make an itch feel more intense. These findings caused scientists to suspect that itch and pain share the same nerve pathways — that perhaps itch was a weaker form of pain. Researchers now believe that although itch and pain may share some of the same nerve receptors, they send messages to the brain via different nerve circuits and pathways. In addition, studies involving brain scans have found that itch and pain generate activity in different areas of the brain’s frontal lobe.  

More recently, scientists have learned that itch has at least two devoted nerve pathways.  One is used when an itch is triggered by histamine, a substance released by the body’s cells in response to allergens such as ragweed pollen, insect venom, or poison ivy. The other pathway is activated by non-histamine sources.  Researchers have used the main ingredient in practical jokers’ itching powder — a tropical herb called cowhage — to explore non-histamine-based chronic itch. The presence of two separate pathways helps explain why anti-histamine drugs often fail to bring relief. Insight into how these pathways convey messages to the brain may help scientists develop more effective treatments for specific types of itch. 

The realization that itch and pain are two distinct sensations led scientists to ask how are they different? The discovery of a potential “itch gene” in mice, called the gastrin-releasing peptide receptor (GRPR), may provide some answers. When mice bred to lack this gene were injected with a painkiller that usually induces itch, they did not scratch. Likewise, when researchers gave normal mice the painkiller along with a chemical that blocked GRPR, they also did not scratch. These findings suggest that GRPR is important for itch but not for pain. If these results are confirmed and GRPR nerve cells can be similarly affected in humans, scientists may be able to develop pain treatments that don’t cause itchy skin. 

For people whose itches are satisfied by a scratch, scientists are learning why. Brain imaging studies have found that scratching both increases activity in an area associated with compulsive behavior and reduces activity in one linked with unpleasant emotions.  These findings may explain why scratching an itch is both compulsive and pleasurable. 


References

Han L., Ma C., Liu Q., et al. A Subpopulation of Nociceptors Specifically Linked to Itch. Nature Neuroscience. 10.1038/nn.3289 (2012).

Niemeier V, Kupfer J, Gieler U. (2000) Observations during an itch inducing lecture. Dermatology and Psychosomatics. 1:15-18.

McGlone F, Rukweid R, Hitchcock D, Howard M. (2003) Histamine induced discriminative and affective responses revealed by functional MRI. In Itch: Basic Mechanism and Therapy. New York: Marcel Dekker: 53-62.

Davidson S, Zhang X, Yoon CH, Khasabov SG, Dimone DA, Giesler GJ. (2007) The itch-producing agents histamine and cowhage activate separate pupulations of primate spinothalamic tract neurons. Journal of Neuroscience. 27:10007-100014.

Sun YG, Zhao ZQ, MengXL, Yin J, Liu XY, Chen ZF. (2009) Cellular basis of itch sensation. Science. 325: 1531-1534.

Yosipovitch G, Ishiuji Y, Patel TS, Hicks MI, Oshiro Y, Kraft RA, Winnicki E, Coghill RC. (2008) The brain processing of scratching. Journal of Investigative Dermatology. 128:1806-1811.

Further Reading

Davidson S, Giesler G. (2010) The multiple pathways for itch and their interactions with pain. Trends in Neuroscience.

Gawande, A. (June 30, 2008) The itch. The New Yorker.

Gieler U, Walter B. Chronic itching: causes and cures. June 26, 2008. Scientific American Mind.

Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. (2006) The neurobiology of itch. Nature Reviews Neuroscience. 7:535-547.

Sanders, Laura. (2008) Itch. Science News. 174:16-19.