Impaired Junctions and Invaded Macrophages in Oral Epithelia With Oral Pain

Reiko U. Yoshimoto, Reona Aijima, Yukiko Ohyama, Junko Yoshizumi, Tomoko Kitsuki, Yasuyoshi Ohsaki, Ai Lin Cao, Atsushi Danjo, Yoshio Yamashita, Tamotsu Kiyoshima, Mizuho A. Kido

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Recurrent or chronic oral pain is a great burden for patients. Recently, the links between epithelial barrier loss and disease were extended to include initiation and propagation. To explore the effects of pathohistological changes in oral epithelia on pain, we utilized labial mucosa samples in diagnostic labial gland biopsies from patients with suspected Sjögren’s syndrome (SS), because they frequently experience pain and discomfort. In most labial mucosa samples from patients diagnosed with SS, disseminated epithelial cellular edema was prevalent as ballooning degeneration. The disrupted epithelia contained larger numbers of infiltrating macrophages in patients with oral pain than in patients without pain. Immunohistochemistry revealed that edematous areas were distinct from normal areas, with disarranged cell–cell adhesion molecules (filamentous actin, E-cadherin, β-catenin). Furthermore, edematous areas were devoid of immunostaining for transient receptor potential channel vanilloid 4 (TRPV4), a key molecule in adherens junctions. In an investigation on whether impaired TRPV4 affect cell–cell adhesion, calcium stimulation induced intimate cell–cell contacts among oral epithelial cells from wild-type mice, while intercellular spaces were apparent in cells from TRPV4-knockout mice. The present findings highlight the relationship between macrophages and epithelia in oral pain processing, and identify TRPV4-mediated cell–cell contacts as a possible target for pain treatment.

Original languageEnglish
Pages (from-to)245-256
Number of pages12
JournalJournal of Histochemistry and Cytochemistry
Issue number4
Publication statusPublished - Apr 1 2019

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Histology


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