Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice

Neuroreport. 2023 Feb 1;34(3):165-169. doi: 10.1097/WNR.0000000000001877. Epub 2023 Jan 20.


Objectives: Pain is the most common cause of seeking healthcare and the leading cause of disability worldwide. Although cannabidiol and transcutaneous electrical nerve stimulation (TENS) are effective and safe strategies for treating chronic pain, the combined effect of these interventions remains overlooked. To compare the isolated and combined effect of cannabidiol and TENS in the treatment of experimental neuropathic and inflammatory pain.

Methods: Swiss mice were subjected to chronic constriction injury (CCI)-induced neuropathic or carrageenan-induced inflammatory pain models. Cannabidiol or TENS alone and the combination of these therapies were administered once. The nociceptive threshold was measured by the von Frey test. IL-1β, TNF-α and IL-10 cytokine levels were measured by ELISA from spinal cord samples.

Results: Combined, cannabidiol and TENS potentiate antinociception only in neuropathic pain. IL-1β and TNF-α levels were similarly reduced when TENS or cannabidiol were administered alone or in combination. However, only cannabidiol and TENS combined increased IL-10 levels.

Conclusions: Our findings indicated TENS and cannabidiol combined were effective in potentiating antinociception in a neuropathic pain model, an effect potentially associated with spinal IL-10 upregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabidiol* / pharmacology
  • Interleukin-10
  • Mice
  • Neuralgia* / therapy
  • Transcutaneous Electric Nerve Stimulation*
  • Tumor Necrosis Factor-alpha


  • Cannabidiol
  • Interleukin-10
  • Tumor Necrosis Factor-alpha