Itchy wool sweaters explained: Scientists uncover itch-specific nerve cells in skin
This is an artist's rendition of nerve cells monitoring the surface of the skin where they may encounter pain stimulants like capsaicin, found in hot peppers, and itch stimulants like histamine. Credit: Copyright Tim Phelps, Department of Art as Applied to Medicine, Johns Hopkins University, 2012
Johns Hopkins researchers have uncovered strong evidence that mice have a specific set of nerve cells that signal itch but not pain, a finding that may settle a decades-long debate about these sensations, and, if confirmed in humans, help in developing treatments for chronic itch, including itch caused by life-saving medications.
At the heart of their discovery is a type of sensory nerve cell whose endings receive information from the skin and relay it to other nerves in the spinal cord, which then coordinates a response to the stimulus. Published online Dec. 23 in Nature Neuroscience, a report on the research suggests that even when the itch-specific nerve cells receive stimuli that are normally pain-inducing, the message they send isn't "That hurts!" but rather "That itches!"
Pain and itch are both important sensations that help organisms survive. And pain is arguably more important because it tells us to withdraw the pained body part in order to prevent tissue damage. But itch also warns us of the presence of irritants, as in an allergic reaction. However, "when either of these sensations continues for weeks or months, they are no longer helpful. We even see patients stop taking life-saving medications because they cause such horrible itchiness all over," says Xinzhong Dong, a Howard Hughes early career scientist and associate professor of neuroscience at the Institute of Basic Biomedical Sciences at the Johns Hopkins University School of Medicine. "And sometimes when we try to suppress chronic pain, with morphine for example, we end up causing chronic itchiness. So the two sensations are somehow related, and this study has begun to untangle them," he says.
Because nerve cells send their messages as electrical currents that flow through them just as they would through wires, scientists can plug tiny monitors into individual nerve cells to detect the moment of stimulation. The scientific controversy over pain and itch centers around a group of nerve cells known to respond electrically to painful stimuli such as molecules of capsaicin, the fiery ingredient in chili peppers. A small subset of these nerve cells also responds electrically to itchy stimuli because they have on their surfaces receptors for molecules like histamine. One of these itchy receptors, called MrgA3, binds the anti-malaria drug chloroquine, causing serious itchiness in many patients.
Sensory nerve scientists have not known whether the nerves with itchy receptors and pain receptors were actually sending both types of messages to the brain, or just itch messages. What the current study found is that, in nerves with the itchy receptor MrgA3, electrical signals sent in response to both painful and itchy stimuli are interpreted by the brain as itch.
To reach this conclusion, the researchers first used a genetic trick to label the MrgA3 cells in mice with a glowing protein that allowed them to see the cells under the microscope. Aided by the glow, they were able to plug in those tiny electricity monitors and watch nerve cell responses to different stimuli. The cells transmitted electrical signals when the mice were exposed to itch-inducing chloroquine and histamine, as well as pain-inducing capsaicin and heat. Based on this result, the researchers tentatively concluded that the cells could send both pain and itch signals.
In the next experiment, the researchers monitored the behavioral responses of mice to the different stimuli. As expected, when the tails of normal mice were placed in hot water, they quickly pulled them out; when normal mice were given a bit of chloroquine or histamine, they scratched vigorously with their hind legs.
Then, to examine the role of MrgA3 cells in pain and itch, the scientists selectively killed MrgA3 nerve cells in adult mice and retested their responses. Presumably, the researchers noted, because MrgA3 cells are only a small fraction of all pain-sensing nerve cells, the mice had normal withdrawal responses to painful stimuli like hot water. However, when exposed to itchy stimuli, their scratching responses were reduced to varying degrees depending on the stimulus, most significantly in response to chloroquine. The fact that some stimuli still caused scratching suggested to the scientists that MrgA3 cells are not the only ones in the body that respond to itch. "We were convinced that MrgA3 cells are responsible for much of the sensation of itch, but it wasn't yet clear whether MrgA3 cells could also relay painful information," says Dong.
In their final experiments, the scientists used genetic techniques to create mice in which the MrgA3 cells were the only cells in the body capable of responding to capsaicin, that peppery pain-inducing substance. When injected into the cheeks of mice, normal mice massage the area with their forepaws to relieve the hot sensation. When injected into the experimental mice, they vigorously scratched their cheeks with their hind legs, suggesting that this normally painful stimulus had been communicated to the brain—by MrgA3 cells—as itchiness.
"Now that we have disentangled these itchy sensations from painful ones, we should be able to design drugs that target itch-specific nerve cells to combat chronic itchiness," says Dong. "We hope that this will not only provide relief, but also increase people's faithfulness to their drug plans, particularly for deadly diseases like malaria and cancer."
More information: dx.doi.org/10.1038/nn.3289
Journal reference: Nature Neuroscience
Provided by Johns Hopkins University School of Medicine
- Up a little on the left... now, over to the right... Scientists find a source of nonallergic itch Dec 22, 2009 | not rated yet | 0
- Pain and itch connected down deep May 02, 2011 | not rated yet | 0
- Study looks at effect of emotions on pain and itch intensity Mar 16, 2012 | not rated yet | 0
- Burning pain and itching governed by same nerve cells Nov 04, 2010 | not rated yet | 0
- Researchers identify itch-specific neurons in mice, hope for better treatments Aug 06, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Study shows premature birth interrupts vital brain development processes leading to reduced cognitive abilities
Researchers from King's College London have for the first time used a novel form of MRI to identify crucial developmental processes in the brain that are vulnerable to the effects of premature birth. This new study, published ...
Neuroscience 2 hours ago | not rated yet | 0 |
While the effects of acute stroke have been widely studied, brain damage during the subacute phase of stroke has been a neglected area of research. Now, a new study by the University of South Florida reports that within a ...
Neuroscience 4 hours ago | not rated yet | 0 |
Over the past few decades, neuroscientists have made much progress in mapping the brain by deciphering the functions of individual neurons that perform very specific tasks, such as recognizing the location ...
Neuroscience 7 hours ago | 5 / 5 (5) | 0 |
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
Neuroscience May 18, 2013 | 5 / 5 (1) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
Neuroscience May 17, 2013 | 4 / 5 (1) | 0 |
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
1 hour ago | not rated yet | 0 |
A Saudi man who had contracted the coronavirus has died, raising the death toll in the kingdom from the SARS-like virus to 16, the health ministry announced on Monday on its Internet website.
1 hour ago | not rated yet | 0
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
1 hour ago | 5 / 5 (3) | 0 |
(Medical Xpress)—Individuals who learn two languages at an early age seem to switch back and forth between separate "sound systems" for each language, according to new research conducted at the University of Arizona.
1 hour ago | 5 / 5 (2) | 0 |
Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired
Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...
1 hour ago | 5 / 5 (1) | 1 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
2 hours ago | not rated yet | 0 |