Poison ivy, bug bites, allergies — just hearing those words can make you want to scratch. But even though we all itch, and we all scratch, we don’t know very much about what is happening in our brains when we do so.
New work by researchers, including one in Pittsburgh, is attempting to figure it out.
Sarah Ross, a physiologist and itch specialist at the University of Pittsburgh’s Neurology Department and Pain Center, said the neuroscience community has developed new tools that are allowing researchers to learn more about how neurocircuits work. And in recent years, funding agencies have pumped more money into itch-related research, which has helped researchers, such as Ross, who are at the forefront of new sensory science.
"We are interested in understanding how sensory information such as hot, cold, itch, pain," she said, "how that information is detected on your skin and integrated in the spinal cord."
While the neural pathways of itch and pain are distinct from each other, they are connected. Ross said they are two sides of the same coin.
Itch and pain are both alarm signals that warn our bodies that there could be something harming us. That’s similar. But they trigger different behavioral responses that may feel involuntary. So if you put your hand on a hot stove, your instinct would be to pull it away, but if something is triggering itch, the reflex is to scratch.
Our nervous system is made up of billions of individual nerve cells, or neurons. They’re wired together. Itch is first detected by nerve cells that have terminals in our skin. When they detect an itchy substance they send that information to the spinal cord, in turn, sends it to the brain.
"Once it gets to the brain it goes to many different regions of the cortex," Ross said. "One part of the cortex might be telling you where the itch is another part of the cortex might be telling you I don’t like this, this feels awful, and then another part of the cortex, you know the motor cortex, might be saying, let's get rid of this, I want to scratch it away."
That may sound like many steps — and it is — but Ross said it happens quickly.
"From the moment that the sensory neuron detects the itch until you respond could be very fast in the sense that the information passing from neuron to another neuron is a millisecond process, so even though there may be 10 steps, each one is a millisecond," she said, "so it’s a very, very fast process."
What researchers don’t yet know is why something causes you to scratch yourself. Ross and her colleagues are trying to figure out how the neurons are integrating that information and causing the scratch behavior.
They’re doing that using genetically engineered mice.
They selectively label and manipulate groups of nerve cells in these mice to make it so certain nerve cells are green and glow in the dark. These cells can be activated with drugs allowing the scientists to trace the neural circuits and figure out how they do what they do.
"We inhibit that one part of the neural circuit, and we see do the mice still respond to an itchy substance, do they still respond to a painful substance or now or can they no longer respond," she said.
They also use electrophysiology, a way of listening to the activity of particular nerve cells while researchers manipulate some aspect of the input. They might record from a population of nerve cells that are the ones that respond to itch, and then if they add an itchy substance they could hear those neurons firing much more rapidly. They use very fine electrodes and just touch the edge of the nerve cell membrane and then we can hear the electric activity that’s in the cell.
But what do those sounds mean?
"We might have a hypothesis that those itch neurons are conveying information from a particular kind of projection neuron," Ross said. "We could record from that particular kind of projection neuron and then test the hypothesis that if we add an itchy substance those are the neurons that are going to respond."
Earlier this summer, Ross and her colleagues published a paper in the scientific journal Neuron reporting that although it may not feel like it when you can’t stop scratching yourself, the body often takes action to control itching. They identified a neuron that tries to stop itching by partially blocking the neural signal going from the itch site to the brain through the production of an opiate.
"Those neurons function to inhibit itch. They block itch," Ross said. "That’s why when you lose those neurons, itch is abnormally high, and what we discovered about those cells was two important things: First thing we discovered is those are the neurons in the spinal cord that are normally releasing dynorphin, which is a kappa-opiod and kappa-opiods we show inhibit itch just like mu opidiods like morphine inhibit pain so we think the kappa system is an endogenous system that inhibits itch, and we’re going to be able to use that to develop drugs that inhibit itch."
That’s a good thing. While we all itch for lots of reasons — mosquito bites in the summer and wool sweaters in the winter are common ones. Dermatitis or neuropathic itch can be a severe problem for lots of people. There are hundreds of disease conditions, including several mental health diagnoses associated with itch. Ross and her colleagues at Pitt aren’t looking at that — they are looking at this from the bottom up, and as they move further into the nervous system, they hope to get to some of the other mysteries of itch.
"If you see somebody else that’s scratching you might start scratching," Ross said. "That’s because itch is contagious. We know that to be true, but we have no understanding of how that works, and there may be some diseases where that type of itch is heightened, but we don’t understand that very well yet."