Methylene blue induces an analgesic effect by significantly decreasing neural firing rates and improves pain behaviors in rats

Seung Won Lee, Sun Wook Moon, Jin Sung Park, Hye Rim Suh, Hee Chul Han

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Methylene blue (MB) is a blue cationic thiazine dye and currently used in different medical settings. Notably, there have been several attempts to introduce MB for attenuating pain in the last decade. Some clinical studies reported remarkable results, which, however, have been much debated. In addition, accumulating evidence have revealed that MB diminishes voltage-gated sodium channel currents. Accordingly, in the present study, we conducted in vivo experiments, including in vivo single nerve recording and behavioral test, to investigate whether MB dampens neural firing rates and ultimately contributes to pain relief. As a result, neural firing rates significantly decreased and finally converged to zero after MB administration. This event lasted longer than that of lidocaine and was dose-dependently modulated. Furthermore, there was a marked improvement in pain behaviors. The withdrawal threshold and latency of hind paws significantly rose post-MB administration. Therefore, these results demonstrate that MB lessens pain by significantly weakening neural excitability, which implies a strong possibility that this dye may be developed as a pain-relieving medication in the future. This is the first in vivo study to elucidate the effect of MB on nerves and pain relief.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalBiochemical and biophysical research communications
Publication statusPublished - 2021 Feb 19

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea ( NRF ) funded by the Ministry of Education (grant number: NRF-2019R1I1A1A01063196).

Publisher Copyright:
© 2021


  • In vivo single nerve recording
  • Lidocaine
  • Methylene blue
  • Neural firing rate
  • Pain reduction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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