Study Identifies Itch-specific Nerves

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Scientists have been looking for itch-specific nerves for decades. New research from investigators at Johns Hopkins University and Yale University in the United States and several universities in China has identified sensory neurons in mice that are dedicated to relaying itchy sensations from the top layers of skin to the spinal cord [1].

In 1835, Johannes Peter Müller proposed the law of specific nerve energies. It stated that everything we feel and experience relies on the stimulation of particular neuronal pathways — and thus that the actual, external stimulus is irrelevant. He wrote:

The same cause, such as electricity, can simultaneously affect all sensory organs, since they are all sensitive to it; and yet, every sensory nerve reacts to it differently; one nerve perceives it as light, another hears its sound, another one smells it; another tastes the electricity, and another one feels it as pain and shock.

But how to divorce the stimulus from the nerve it stimulates to test this idea? As reported in a recent paper in Nature Neuroscience, an international team of researchers started by labeling a small subset of neurons in the dorsal root ganglion in mice [2]. The dorsal root ganglion is the home of neurons that mediate sensory signals, and the subset of neurons these scientists labeled is known to respond to stimuli that induce both pain and itch. They showed that these neurons exclusively innervate the epidermis — the outermost layer of the skin — and that they connect to a type of neuron in the spinal cord previously known to mediate itching. Unlike pain, which can arise from deeper tissues like muscle, bone, and organs, itch arises exclusively from the skin. The researchers go on to demonstrate that for the first time, they have identified neurons that are responsible specifically for feeling itchy.

Itch-specific neurons have been sought for many years. Because there are neurons that respond to both painful and itchy stimuli, it has been controversial whether neurons that mediate itch exclusively exist at all. These researchers found that ablating only their labeled subset of nerves did not alter pain reception, so these neurons were not required in order for the mice to feel pain. However, ablating these cells did reduce all kinds of itchiness — itchiness induced by the antimalarial drug chloroquinone, itchiness induced by histamine, itchiness induced by dry skin, and itchiness associated with allergic chronic conditions like allergic conjunctivitis and allergic contact dermatitis. Eliminating these cells markedly reduced itch, but did not abolish it completely, so the authors speculate that other types of neurons contribute to itchiness as well. But their best proof that these neurons elicit only itch came from an experiment where they injected the mice with capsaicin, the compound that makes spicy peppers spicy and a standard stimulus used in pain research to elicit pain. Upon stimulation with capsaicin, these neurons transmitted an itchy signal. The mice scratched.

The authors hope that their identification of itch specific neurons will help develop better therapies to combat itchiness. Currently, treatments for both chronic and acute itchiness rely on medications such as corticosteroid creams and oral antihistamines, light therapy (phototherapy), topical anesthetics such as lidocaine or benzocaine, and ointments and lotions such as menthol, camphor or calamine [2].

References

1. Han et al. A subpopulation of nociceptors specifically linked to itch. Nat Neurosci. 2012 Dec 23;16(2):174-82. doi: 10.1038/nn.3289. Epub 2012 Dec 23.
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2. Itchy skin (pruritus): Treatments and drugs. Mayo Clinic. Accessed 2013 Jan 8.