Itching is an unpleasant sensation that drives us to scratch reflexively in an effort to remove harmful substances from our body. It’s also how I get most of my physical activity for the day. Not being able to scratch an itch is intensely frustrating and many scientists have long described itch as the milder cousin of pain.
But a team of scientists from Washington University’s Pain Center (I wonder if they have problems with recruitment) have discovered a group of neurons in the spines of mice that are specific to itch but not to pain. Remove them, and mice hardly ever scratch when they’re exposed to itchy chemicals, even though they can still feel pain as well as any normal mouse.
The discovery settles a long-standing debate about whether itch and pain are governed by separate neural systems. It confirms the so-called “labelled line” theory, which says that both sensations depend on different groups of nerve cells.
Two years ago, Yan-Gang Sun and Zhong-Qiu Zhao discovered an itch-specific gene called GRPR that is activated in a small group of neurons in the spinal cords of mice. Without a working copy of this gene, mice became immune to itching but they still responded normally to heat, pressure, inflammation and the noxious flavour of mustard. The duo even managed to stop mice from scratching by injecting them with a chemical that blocks GRPR.
But neurons that activate an itch-specific gene aren’t necessarily restricted to conveying the sensations of itching – they could also be involved in pain. To test that idea, Sun and Zhao injected mice with a nerve poison called bombesin-saporin, which specifically kills neurons that use GRPR. Without these neurons, the mice resisted a wide variety of substances that cause normal mice to scratch furiously, even though their movements were generally unaffected. Just compare the two mice in the video below – both have been injected with an itching agent but the one on the left lacks any working GRPR neurons.
However, even bereft of GRPR neurons, the mice felt pain just as any other mouse would, reacting normally to heat, pressure and noxious chemicals like mustard oil and capsaicin, the active component of chillies. Clearly, these neurons are specific to itch.
A couple of weeks ago, I wrote about propranolol, a drug that can erase the emotion of fearful memories. When volunteers take the drug before recalling a scary memory about a spider, it dulled the emotional sting of future recollections. It’s not, however, a mind-wiping pill in the traditional science-fiction sense, and it can’t erase memories as was so widely reported by the hysterical mainstream media.
The research that’s published today is a different story. Jin-Hee Han from the University of Toronto has indeed found a way to erase a specific fearful memory, but despite the superficial similarities, this is a very different story to the propranolol saga. For a start, Han worked in mice not humans. And unlike the propranolol researchers, who were interested in developing ways of treating people with post-traumatic stress disorder, Han’s goal was to understand how memories are stored in the brain. Erasing them was just a step towards doing that.
Han’s found that a protein called CREB is a molecular beacon that singles out neurons involved in remembering fearful experiences. When a rat experiences something scary, the CREB-neurons in a part of its brain called the amygdala are responsible for storing that memory – for producing what neuroscientists call its “trace”. When Han killed the amygdala’s CREB-neurons, he triggered selective amnesia in the rats, abolishing the specific fears they had been trained to feel. The memory loss was permanent.
This is a major piece of work. Scientists have long believed that memories are represented by specific collections of neurons. But these neurons don’t occur in a neat, tidy clump; they’re often widely spread out, which makes finding the cells that make up any particular memory incredibly challenging. Han has done this by using the CREB protein as a marker. And in doing so, he had highlighted the vital role of this protein in our memories.
I stress again that this isn’t about erasing memories in and of itself. Doing so is just a means to an end – identifying a group of neurons involved in storing a specific memory. For reasons that should become clear in this article, Han’s technique isn’t exactly feasible in humans! Whether this will stop the inevitable run-for-the-hills editorials is perhaps unlikely, but enough speculation: on with the details.