Tag Archives: itch

New research finds the neurons that makes mice itchy

New research is looking into how our bodies sense and transmit itchiness to the brain.

Light touches play an important role in our daily lives. Between cuddling, picking up fragile objects, and performing tasks that require precision, we use the sensation to guide many of our activities. It’s also an essential part of the body’s defense system, telling us, among others, if we’re covered in biting insects such as ticks or mosquitoes — via that oh-so-pleasant sensation of itchiness.

Creepy crawlies

“The takeaway is that this mechanical itch sensation is distinct from other forms of touch and it has this specialized pathway within the spinal cord,” says Salk Institute Professor Martyn Goulding, senior author of the new study.

The team looked at how neurons in the spinal cord carry these itchy signals to the brain. They hope that the findings will help lead to new drugs to treat chronic itch, which occurs in such conditions as eczema, diabetes, and even some types of cancer.

Goulding and his colleagues had previously found a set of inhibitory neurons in the spinal cord that keep the itchiness pathway locked down most of the time. Inhibitory neurons act as brakes on neural circuits, dampening their activity. Without these neurons — which produce the neurotransmitter neuropeptide Y (NPY) — the pathway is constantly active, causing chronic itching.

What the team wanted to find out know was how the signal encoding this sensation is transmitted to the brain, making us feel the itch. One of the team’s hypotheses was that when NPY inhibitory neurons are missing, the nerve bundles in the spinal cord that transmit light touch get stuck on the “on” setting — which creates a self-amplifying loop. The team identified a population of such (excitatory) neurons in the spinal cord that express the receptor for NPY, the so-called Y1 spinal neurons

To test if these were indeed behind the self-amplifying loop of itchiness, the team selectively removed the NPY “brake” and Y1 “accelerator” neurons in mice to see the effects.

Without Y1 neurons, they report, the mice didn’t scratch, not even in response to light-touch stimuli that normally make them scratch. When the team gave them drugs to activate the Y1 neurons, the mice scratched spontaneously even in the absence of any touch stimuli. The team was then able to link NPY neurotransmitter levels to Y1 neuron excitability — showing that NPY controls our sensitivity to light touch. The findings are also supported by other research which found that people with psoriasis have lower than average levels of NPY.

While the study shows how itchy signals go through the spinal cord, more research is needed to understand the full pathway. There are other neurons that likely mediate its transmission and final response in the brain, the team explains.

“By working out mechanisms by which mechanical itch is signaled under normal circumstances, we might then be able to address what happens in chronic itch,” says David Acton, a postdoctoral fellow in the Goulding lab and the study’s first author.

The paper “Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch” has been published in the journal Cell Reports.

Scientists discover molecular trigger for itch

An itch is a sensation that causes the desire or reflex to scratch. Researchers have long tried to characterize itch, but in its typical annoying fashion, the sensation resisted any such attempts. For a very long time, the itch has been thought of as a low-level form of pain, but now, a new study conducted on mice suggests that it is indeed a distinct sensation, with a dedicated neural circuit linking cells in the periphery of the body to the brain.

itchNeuroscientists Mark Hoon and Santosh Mishra of the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, tried to find the exact molecule which triggers the sensation of itch by screening genes in sensory neurons that are activated by touch, heat, pain and itch. They found that one particular protein, called natriuretic polypeptide b, or Nppb, was expressed in only a subset of these neurons.

Mutant mice lacking this this protein, did not respond to itch-inducing compound – but interestingly enough, they didn’t respond to heat and pain. But what’s even more interesting is that when Nppb was injected into the mice, it send them into a scratching frenzy. This occurred both in the mutants and in control mice.

“Our research reveals the primary transmitter used by itch sensory neurons and confirms that itch is detected by specialized sensory neurons,” says Hoon.

According to Glenn Giesler, a neuroscientist at the University of Minnesota in Minneapolis, the result “explains problems in the literature and provides a very testable hypothesis for how itch works”.

Previous research suggested that gastrin-releasing peptide, or GRP, was the neurotransmitter behind itches, but as Hoon and Misha showed (almost beyond the shadow of a doubt) is that GRP is not the primary trigger, but is still involved in the process, and injecting GRP into mice lacking either Nppb or its receptor did produce strong scratching responses.

Furthermore, mice in which GRP receptors were inhibited did not engage in scratching behaviour, even with spinal-cord injection of Nppb. This seems to suggest that GRP-releasing neurons are downstream of Nppb in the transmission of the itch sensation.

“This model fits better with what everyone else is seeing,” says Sarah Ross, a neuroscientist at the University of Pittsburgh in Pennsylvania.

The neural pathways are similar, though not identical, to those in mice. It remains to be seen if Nppb plays the same role in humans, or if there is something different involved.

“Antihistamines work for a few forms of itch, but for the vast majority they do nothing,” he says. “This research introduces a brand new target for clinical treatment.”

Via Nature