Newly Published
Pain Medicine  |   February 2018
Endothelin Signaling Contributes to Modulation of Nociception in Early-stage Tongue Cancer in Rats
Author Notes
  • From the Department of Clinical Medicine (A.F., R.A., Y.Y.) and the Department of Physiology (M.S., A.K., K.H., K.I.), Nihon University School of Dentistry, Tokyo, Japan.
  • Submitted for publication August 3, 2017. Accepted for publication January 22, 2018.
    Submitted for publication August 3, 2017. Accepted for publication January 22, 2018.×
  • Research Support: Supported in part by research grants from the Sato and Uemura Funds from the Nihon University School of Dentistry (Tokyo, Japan), a grant from the Dental Research Center in Nihon University School of Dentistry, Nihon University Multidisciplinary Research Grant (2016 and 2017), and the Ministry of Education, Culture, Sports, Science and Technology–supported Program for the Strategic Research Foundation at Private Universities (2013–2017).
    Research Support: Supported in part by research grants from the Sato and Uemura Funds from the Nihon University School of Dentistry (Tokyo, Japan), a grant from the Dental Research Center in Nihon University School of Dentistry, Nihon University Multidisciplinary Research Grant (2016 and 2017), and the Ministry of Education, Culture, Sports, Science and Technology–supported Program for the Strategic Research Foundation at Private Universities (2013–2017).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Shinoda: Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. shinoda.masamichi@nihon-u.ac.jp. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Pain Medicine
Pain Medicine   |   February 2018
Endothelin Signaling Contributes to Modulation of Nociception in Early-stage Tongue Cancer in Rats
Anesthesiology Newly Published on February 14, 2018. doi:10.1097/ALN.0000000000002139
Anesthesiology Newly Published on February 14, 2018. doi:10.1097/ALN.0000000000002139
Abstract

Background: Patients with early stage tongue cancer do not frequently complain of tongue pain. Endothelin-1 signaling is upregulated in the cancerous tongue at the early stage. We tested the hypothesis that endothelin-1 signaling contributes to the modulation of tongue nociception.

Methods: Squamous cell carcinoma cells were inoculated into the tongue under general anesthesia. Lingual mechanical sensitivity under light anesthesia using forceps from days 1 to 21 (n = 8) and the amounts of endothelin-1 and β-endorphin in the tongue on days 6, 14, and 21 (n = 5 to 7) were examined after the inoculation. The effect of endothelin-A or µ-opioid receptor antagonism on the mechanical sensitivity was examined (n = 5 to 7).

Results: Lingual mechanical sensitivity did not change at the early stage (days 5 to 6) but increased at the late stage (days 13 to 14). The amount of endothelin-1 increased (25.4 ± 4.8 pg/ml vs. 15.0 ± 5.2 pg/ml; P = 0.008), and endothelin-A receptor antagonism in the tongue induced mechanical hypersensitivity at the early stage (51 ± 9 g vs. 81 ± 6 g; P = 0.0001). The µ-opioid receptor antagonism enhanced mechanical hypersensitivity (39 ± 7 g vs. 81 ± 6 g; P < 0.0001), and the amount of β-endorphin increased at the early stage.

Conclusions: β-Endorphin released from the cancer cells via endothelin-1 signaling is involved in analgesic action in mechanical hypersensitivity at the early stage.