Keratinocytes can modulate and directly initiate nociceptive responses.
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.
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Kyle M
http://orcid.org/0000-0003-0437-9209
KM
Baumbauer
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Jennifer J
JJ
DeBerry
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Peter C
PC
Adelman
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Richard H
RH
Miller
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Junichi
J
Hachisuka
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Kuan Hsien
KH
Lee
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Sarah E
SE
Ross
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
H Richard
HR
Koerber
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Brian M
BM
Davis
Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
Kathryn M
KM
Albers
D000200:Action Potentials; D000818:Animals; D004817:Epidermis / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D059226:Nociceptive Pain; D011984:Sensory Receptor Cells / Q000502:physiology*; D014110:Touch
epidermal; keratinocyte; mouse; neuroscience; nociceptor; optogenetics; pain; sensory neuron