TY - JOUR
T1 - Selective keratinocyte stimulation is sufficient to evoke nociception in mice
AU - Pang, Zixuan
AU - Sakamoto, Takashi
AU - Tiwari, Vinod
AU - Kim, Yu Shin
AU - Yang, Fei
AU - Dong, Xinzhong
AU - Güler, Ali D.
AU - Guan, Yun
AU - Caterina, Michael J.
N1 - Funding Information:
Supported by grants from the NIH (NIAMS AR-62826), funding from the Neurosurgery Pain Research Institute at Johns Hopkins, and a gift from the Kao Corporation to M. J. Caterina and by a grant from the NIH (NS70814) to Y. Guan.
Publisher Copyright:
© 2015 Lippincott Williams and Wilkins. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - The skin epidermis is densely innervated by peripheral sensory nerve endings. Nociceptive neurons, whose terminals are in close contact with epidermal keratinocytes, can be activated directly by noxious physical and chemical stimuli to trigger pain. However, whether keratinocytes can signal acutely to sensory nerve terminals to initiate pain in vivo remains unclear. Here, using the keratin 5 promoter to selectively express the capsaicin receptor TRPV1 in keratinocytes of TRPV1-knockout mice, we achieved specific stimulation of keratinocytes with capsaicin. Using this approach, we found that keratinocyte stimulation was sufficient to induce strong expression of the neuronal activation marker, c-fos, in laminae I and II of the ipsilateral spinal cord dorsal horn and to evoke acute paw-licking nocifensive behavior and conditioned place aversion. These data provide direct evidence that keratinocyte stimulation is sufficient to evoke acute nociception-related responses.
AB - The skin epidermis is densely innervated by peripheral sensory nerve endings. Nociceptive neurons, whose terminals are in close contact with epidermal keratinocytes, can be activated directly by noxious physical and chemical stimuli to trigger pain. However, whether keratinocytes can signal acutely to sensory nerve terminals to initiate pain in vivo remains unclear. Here, using the keratin 5 promoter to selectively express the capsaicin receptor TRPV1 in keratinocytes of TRPV1-knockout mice, we achieved specific stimulation of keratinocytes with capsaicin. Using this approach, we found that keratinocyte stimulation was sufficient to induce strong expression of the neuronal activation marker, c-fos, in laminae I and II of the ipsilateral spinal cord dorsal horn and to evoke acute paw-licking nocifensive behavior and conditioned place aversion. These data provide direct evidence that keratinocyte stimulation is sufficient to evoke acute nociception-related responses.
KW - Keratinocyte
KW - Skin
KW - Transgenic pain
KW - Transient receptor potential
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U2 - 10.1097/j.pain.0000000000000092
DO - 10.1097/j.pain.0000000000000092
M3 - Article
C2 - 25790456
AN - SCOPUS:84943812640
VL - 156
SP - 656
EP - 665
JO - Pain
JF - Pain
SN - 0304-3959
IS - 4
ER -