Lewis and Grandl
offer context and note the significance of work by by Feng et al.
It is well known that aging is accompanied by the death of specific cell types that function as sensors of outside signals and that this cell death leads to deficits in our ability to detect these signals. For example, age-associated loss of sensory hair cells and/or spiral ganglia neurons in the inner ear leads to progressive hearing loss, particularly of high frequencies. Similarly, death of photoreceptors in the retina of the eye is a key aspect of the pathogenesis of age-related macular degeneration, the leading cause of vision impairment in individuals older than 60 years of age. Feng et al. now identify an unusual link between age-related loss of a sensory cell type and aberrant sensory processing: During aging, the loss of specialized skin cells called Merkel cells results in alloknesis, the pathological sensation of itch in response to innocuous mechanical stimuli...
The finding that Merkel cells normally protect against mechanical itch is notable because it is initially counterintuitive. Whereas in other sensory modalities (for example, vision and hearing), a reduction in sensory cell number as a result of cell death leads to a detrimental reduction in sensation, here, death of Merkel cells leads to an increase in unwanted sensation; that is, an otherwise nonaversive stimulus is perceived as potentially harmful.
The Feng et al.
The somatosensory system relays many signals ranging from light touch to pain and itch. Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis. Chemogenetic activation of Merkel cells protected against alloknesis in dry skin. This study reveals a previously unknown function of the cutaneous touch receptors and may provide insight into the development of alloknesis.
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