Non-Psychoactive Cannabinoid Modulation of Nociception and Inflammation Associated with a Rat Model of Pulpitis

Biomolecules. 2023 May 16;13(5):846. doi: 10.3390/biom13050846.


Despite advancements in dental pain management, one of the most common reasons for emergency dental care is orofacial pain. Our study aimed to determine the effects of non-psychoactive Cannabis constituents in the treatment of dental pain and related inflammation. We tested the therapeutic potential of two non-psychoactive Cannabis constituents, cannabidiol (CBD) and β-caryophyllene (β-CP), in a rodent model of orofacial pain associated with pulp exposure. Sham or left mandibular molar pulp exposures were performed on Sprague Dawley rats treated with either vehicle, the phytocannabinoid CBD (5 mg/kg i.p.) or the sesquiterpene β-CP (30 mg/kg i.p.) administered 1 h pre-exposure and on days 1, 3, 7, and 10 post-exposure. Orofacial mechanical allodynia was evaluated at baseline and post-pulp exposure. Trigeminal ganglia were harvested for histological evaluation at day 15. Pulp exposure was associated with significant orofacial sensitivity and neuroinflammation in the ipsilateral orofacial region and trigeminal ganglion. β-CP but not CBD produced a significant reduction in orofacial sensitivity. β-CP also significantly reduced the expression of the inflammatory markers AIF and CCL2, while CBD only decreased AIF expression. These data represent the first preclinical evidence that non-psychoactive cannabinoid-based pharmacotherapy may provide a therapeutic benefit for the treatment of orofacial pain associated with pulp exposure.

Keywords: cannabinoids; dental pain; pulpitis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cannabinoids* / pharmacology
  • Cannabis*
  • Facial Pain / complications
  • Facial Pain / drug therapy
  • Inflammation / metabolism
  • Nociception
  • Pulpitis* / complications
  • Pulpitis* / drug therapy
  • Pulpitis* / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Cannabinoids
  • Cannabidiol