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. 2022 Jul 21;27(14):4662.
doi: 10.3390/molecules27144662.

Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients

Yaron Haviv  1 , Olga Georgiev  1   2 , Tal Gaver-Bracha  1   2 , Sharleen Hamad  3 , Alina Nemirovski  3 , Rivka Hadar  3 , Yair Sharav  1 , Doron J Aframian  1 , Yariv Brotman  4 , Joseph Tam  1
Affiliations

Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients

Yaron Haviv et al. Molecules. .

Abstract

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.

Keywords: 2-AG; anandamide; chronic pain; endocannabinoids; migraine; neuropathic pain; orofacial pain; saliva.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cohort distribution according to diagnosis. Diagnoses are grouped according to etiology and characteristics, see Sharav and Benoliel [28]: MMP—Masticatory Myofascial Pain, TMD—Temporomandibular disorder, TMJ—Solely Temporomandibular joint origin, Mig—Migraine, NVOP—Neurovascular orofacial pain (orofacial migraine), TTH—Tension Type Headache (primary headache), PTN—Post Traumatic Neuropathy, TN—Trigeminal neuralgia, PHN—Post Herpetic Neuralgia, PIFP—Persistent idiopathic facial pain, BMS—Burning Mouth Syndrome.
Figure 2
Figure 2
Cohort distribution according to gender.
See this image and copyright information in PMC

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