Journal Article

Keratinocytes can modulate and directly initiate nociceptive responses

Koerber, H Richard, Davis, Brian M, Albers, Kathryn M, DeBerry, Jennifer J, Lee, Kuan Hsien, Miller, Richard H, Hachisuka, Junichi, Baumbauer, Kyle M, Adelman, Peter C, Ross, Sarah E

2015

Overview

How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can directly elicit AP firing in nociceptive as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing. When a person touches a hot saucepan, nerve cells in the skin send a message to the brain that causes the person to pull away quickly. Similar messages alert the brain when the skin comes in contact with an object that is cold or causes pain. These nerve cells also help to transmit information about other sensations like holding a ball. Scientists believe that skin cells may release messages that influence how the nerves in the skin respond to sensations. But it is difficult to distinguish the respective roles of skin cells and nerve cells in experiments because these cells often appear to react at the same time. Researchers have discovered that a technique called optogenetics, which originally developed to study the brain, can help. Optogenetics uses genetic engineering to create skin cells that respond to light instead of touch. Baumbauer, DeBerry, Adelman et al. genetically engineered mice to express a light-sensitive protein in their skin cells. When these skin cells were exposed to light, the mice pulled away just like they would if they were responding to painful contact. This behavior coincided with electrical signals in the nerve cells even though the nerve cells themselves were not light sensitive. In further experiments, mice were genetically engineered to express another protein in their skin cells that prevents the neurons from being able to generate electrical signals. When these skin cells were exposed to light, the surrounding nerve cells produced fewer electrical signals. Together, the experiments show that skin cells are able to directly trigger electrical signals in nerve cells. Baumbauer, DeBerry, Adelman et al.'s findings may help researchers to understand why some patients with particular inflammatory conditions are in pain due to overactive nerve cells.

• Publisher: eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
• Subject: Action Potentials / Animals / epidermal / Epidermis - physiology / keratinocyte / Keratinocytes - physiology / Mice / Neuroscience / Nociceptive Pain / nociceptor / optogenetics / pain / sensory neuron / Sensory Receptor Cells - physiology / Touch