title: Selective keratinocyte stimulation is sufficient to evoke nociception in mice.
abstract: 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.
authors: Departments of Neurosurgery Biological Chemistry Neuroscience Neurosurgery Pain Research Institute Center for Sensory Biology Department of Anesthesiology and Critical Care Medicine Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA Department of Biology, University of Virginia, Charlottesville, VA, USA.
authors: Zixuan
authors: Z
authors: Pang
authors: Takashi
authors: T
authors: Sakamoto
authors: Vinod
authors: V
authors: Tiwari
authors: Yu-Shin
authors: YS
authors: Kim
authors: Fei
authors: F
authors: Yang
authors: Xinzhong
authors: X
authors: Dong
authors: Ali D
authors: AD
authors: Güler
authors: Yun
authors: Y
authors: Guan
authors: Michael J
authors: MJ
authors: Caterina
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D003216:Conditioning, Operant / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004965:Estrogen Antagonists; D008164:Luminescent Proteins; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013629:Tamoxifen; C016601:afimoxifene; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin