Selective keratinocyte stimulation is sufficient to evoke nociception in mice

Zixuan Pang, Takashi Sakamoto, Vinod Tiwari, Yu Shin Kim, Fei Yang, Xinzhong Dong, Ali D. Güler, Yun Guan, Michael J. Caterina

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)656-665
Number of pages10
Issue number4
StatePublished - Apr 1 2015
Externally publishedYes


  • Keratinocyte
  • Skin
  • Transgenic pain
  • Transient receptor potential

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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