Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients

Yaron Haviv*, Olga Georgiev, Tal Gaver-Bracha, Sharleen Hamad, Alina Nemirovski, Rivka Hadar, Yair Sharav, Doron J. Aframian, Yariv Brotman, Joseph Tam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: the endocannabinoid system (ECS) participates in many physiological and pathological processes including pain generation, modulation, and sensation. Its involvement in chronic orofacial pain (OFP) in general, and the reflection of its involvement in OFP in salivary endocannabinoid (eCBs) levels in particular, has not been examined. Objectives: to evaluate the association between salivary (eCBs) levels and chronic OFP. Methods: salivary levels of 2 eCBs, anandamide (AEA), 2-arachidonoylglycerol (2-AG), 2 endocannabinoid-like compoundsN-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed using liquid chromatography/tandem mass spectrometry in 83 chronic OFP patients and 43 pain-free controls. The chronic OFP patients were divided according to diagnosis into musculoskeletal, neurovascular/migraine, and neuropathic pain types. Results: chronic OFP patients had lower levels of OEA (p = 0.02) and 2-AG (p = 0.01). Analyzing specific pain types revealed lower levels of AEA and OEA in the neurovascular group (p = 0.04, 0.02, respectively), and 2-AG in the neuropathic group compared to controls (p = 0.05). No significant differences were found between the musculoskeletal pain group and controls. Higher pain intensity was accompanied by lower levels of AA (p = 0.028), in neuropathic group. Conclusions: lower levels of eCBs were found in the saliva of chronic OFP patients compared to controls, specifically those with neurovascular/migraine, and neuropathic pain. The detection of changes in salivary endocannabinoids levels related to OFP adds a new dimension to our understanding of OFP mechanisms, and may have diagnostic as well as therapeutic implications for pain.

Original languageAmerican English
Article number4662
Issue number14
StatePublished - 21 Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.


  • 2-AG
  • anandamide
  • chronic pain
  • endocannabinoids
  • migraine
  • neuropathic pain
  • orofacial pain
  • saliva


Dive into the research topics of 'Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients'. Together they form a unique fingerprint.

Cite this