{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:13:38Z","timestamp":1787652818534,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Izador I. Cabakoff Research Endowment Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endocannabinoid system is involved in physiological and pathological processes, including pain generation, modulation, and sensation. Its role in certain types of chronic orofacial pain (OFP) has not been thoroughly examined. By exploring the profiles of specific salivary endocannabinoids (eCBs) in individuals with different types of OFP, we evaluated their use as biomarkers and the influence of clinical parameters and pain characteristics on eCB levels. The salivary levels of anandamide (AEA), 2-arachidonoyl glycerol (2-AG), and their endogenous breakdown product arachidonic acid (AA), as well as the eCB-like molecules N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), were assessed in 83 OFP patients and 43 pain-free controls using liquid chromatography\/tandem mass spectrometry. Patients were grouped by diagnosis: post-traumatic neuropathy (PTN), trigeminal neuralgia (TN), temporomandibular disorder (TMD), migraine, tension-type headache (TTH), and burning mouth syndrome (BMS). Correlation analyses between a specific diagnosis, pain characteristics, and eCB levels were conducted. Significantly lower levels of 2-AG were found in the TN and TTH groups, while significantly lower PEA levels were found in the migraine group. BMS was the only group with elevated eCBs (AEA) versus the control. Significant correlations were found between levels of specific eCBs and gender, health-related quality of life (HRQoL), BMI, pain duration, and sleep awakenings. In conclusion, salivary samples exhibited signature eCBs profiles for major OFP disorders, especially migraine, TTH, TN, and BMS. This finding may pave the way for using salivary eCBs biomarkers for more accurate diagnoses and management of chronic OFP patients.<\/jats:p>","DOI":"10.3390\/ijms232113017","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T20:37:58Z","timestamp":1666903078000},"page":"13017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management"],"prefix":"10.3390","volume":"23","author":[{"given":"Shimrit","family":"Heiliczer","sequence":"first","affiliation":[{"name":"Department of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf","family":"Wilensky","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Gaver","sequence":"additional","affiliation":[{"name":"In Partial Fulfillment of DMD Requirements, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Georgiev","sequence":"additional","affiliation":[{"name":"In Partial Fulfillment of DMD Requirements, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharleen","family":"Hamad","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-0119","authenticated-orcid":false,"given":"Alina","family":"Nemirovski","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Hadar","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Sharav","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron J.","family":"Aframian","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-0093","authenticated-orcid":false,"given":"Joseph","family":"Tam","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Haviv","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1080\/17460441.2018.1524458","article-title":"Chronic orofacial pain animal models progress and challenges","volume":"13","author":"Pereira","year":"2018","journal-title":"Expert Opin. 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