We sat down with pain scientists Dr. Cheryl Stucky and Francie Moehring to explore the surprising connections between touch, pain, and your skin's health.
Imagine an itch so intense and persistent that it dominates your every waking moment. For millions suffering from chronic skin conditions like eczema and psoriasis, this is a daily reality. But what if that relentless itch isn't just a surface-level symptom? What if it's a form of chronic pain, a faulty alarm bell ringing incessantly in your nervous system?
This is the frontier of research being explored by scientists like Dr. Cheryl Stucky and Francie Moehring. Their work is revolutionizing our understanding of touch and pain, revealing that the line between a gentle caress, a painful prick, and a maddening itch is far blurrier than we ever imagined.
"By understanding that the relentless itch of eczema is a form of maladaptive pain signaling, we can move beyond creams that only treat the skin's surface."
Our skin is our largest organ, and it's equipped with a sophisticated network of sensors called sensory neurons. These neurons are like a team of specialized reporters, each tuned to a different type of stimulus.
These sensors detect gentle touch, like a breeze or the brush of fabric.
These are your alarm system. They fire signals to your brain in response to potentially damaging stimuli like extreme heat, sharp pressure, or chemical irritants.
For a long time, scientists debated whether itch was just a mild form of pain. We now know it has its own dedicated neural pathways.
Itch has dedicated neural pathways separate from pain signals
The problem arises in chronic conditions. In skin diseases like eczema, the skin barrier is compromised. This allows environmental allergens and irritants to seep in, constantly activating the local "itch reporters." Over time, these neurons don't just fire—they become hypersensitive. They start overreacting to stimuli that shouldn't be irritating, like the light touch of clothing or even changes in temperature. The brain interprets this constant, chaotic signaling not just as an itch, but as a form of persistent, unpleasant sensation—a type of chronic pain.
To truly understand this connection, let's look at a pivotal experiment from the Stucky lab that investigates the mechanisms of chronic itch.
Which specific type of sensory neuron is responsible for the relentless, touch-evoked itching (alloknesis) in a model of eczema?
The team suspected that a specific subset of pain-sensing neurons, those marked by a receptor called MRGPRA3, were the key culprits in signaling chronic itch, especially the kind worsened by light touch.
The researchers designed an elegant series of steps to test their hypothesis.
First, they used a mouse model of eczema. These mice were treated with a topical drug (MC903) that disrupts the skin barrier, causing inflammation, dryness, and intense, chronic itching—mimicking human eczema.
They knew that MRGPRA3 neurons were a potential "suspect." To track them, they used genetically engineered mice where these specific neurons could be activated or silenced using light or drugs (a technique called optogenetics and chemogenetics).
They observed the mice's scratching behavior in two key scenarios: spontaneous itch and touch-evoked itch.
In the eczema model mice, they used a targeted neurotoxin to selectively ablate (destroy) only the MRGPRA3 neurons.
They compared the scratching behavior before and after the destruction of these neurons. If scratching decreased dramatically, it would be strong evidence that these neurons are critical for the chronic itch sensation.
The results were striking. The data below illustrates the core findings.
This table shows how the eczema model significantly increases both spontaneous and touch-evoked scratching.
| Group | Spontaneous Scratches (per 30 min) | Touch-Evoked Scratches (per 10 stimuli) |
|---|---|---|
| Control (Healthy Skin) | 5 | 0.5 |
| Eczema Model | 42 | 4.8 |
After selectively destroying the MRGPRA3 neurons, scratching behavior in the eczema model dropped precipitously.
| Group | Spontaneous Scratches (per 30 min) | Touch-Evoked Scratches (per 10 stimuli) |
|---|---|---|
| Eczema Model (Before) | 40 | 4.5 |
| Eczema Model (After Neuron Ablation) | 12 | 1.1 |
To confirm the link, researchers directly activated MRGPRA3 neurons in healthy mice, which immediately induced scratching.
| Intervention | Resulting Scratching Behavior |
|---|---|
| Activate MRGPRA3 Neurons (Light/Drug) | Immediate, robust scratching |
| No Activation (Control) | No change in behavior |
This experiment was a major breakthrough. It didn't just show that neurons are involved in itch; it pinpointed a specific type of neuron as a primary driver of chronic itch in a disease state. The dramatic reduction in scratching after removing these neurons proves they are not just participants, but essential conductors of the "itch symphony." This offers a clear and promising target for future therapies: instead of just treating skin inflammation, we could develop drugs that selectively calm these overactive MRGPRA3 neurons.
How do scientists perform such precise experiments? Here's a look at some of the essential "reagents" and tools in their toolkit.
Allows scientists to label, activate, or silence specific types of neurons (e.g., MRGPRA3) to determine their function.
A technique that uses light to control neurons that have been genetically engineered to be light-sensitive. It allows for millisecond-precise activation of specific neural pathways.
Uses engineered receptors that are activated by designer drugs. This allows for longer-term (hours) control of neuron activity in awake, behaving animals.
A method that makes neurons glow when they are active. Scientists can watch in real-time to see which populations of neurons "light up" in response to an itch or pain stimulus.
Precise measurements of animal behavior (e.g., counting scratches, observing paw withdrawal from heat) that serve as the ultimate readout for sensation.
The work of Dr. Stucky, Francie Moehring, and their colleagues is more than just academic. It represents a fundamental shift in how we view chronic skin diseases. By understanding that the relentless itch of eczema is a form of maladaptive pain signaling, we can move beyond creams that only treat the skin's surface.
The future lies in targeting the nervous system itself. The goal is to develop treatments that can quiet the faulty alarm bells, providing relief for the millions for whom a gentle touch has become a source of torment. The conversation between our skin and our brain is complex, but science is finally learning how to help it speak more calmly.
The goal is to develop treatments that can quiet the faulty alarm bells, providing relief for the millions for whom a gentle touch has become a source of torment.
Targeting the nervous system to quiet faulty itch signals