Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management

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)...

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Main Authors: Shimrit Heiliczer, Asaf Wilensky, Tal Gaver, Olga Georgiev, Sharleen Hamad, Alina Nemirovski, Rivka Hadar, Yair Sharav, Doron J. Aframian, Joseph Tam, Yaron Haviv
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/21/13017
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author Shimrit Heiliczer
Asaf Wilensky
Tal Gaver
Olga Georgiev
Sharleen Hamad
Alina Nemirovski
Rivka Hadar
Yair Sharav
Doron J. Aframian
Joseph Tam
Yaron Haviv
author_facet Shimrit Heiliczer
Asaf Wilensky
Tal Gaver
Olga Georgiev
Sharleen Hamad
Alina Nemirovski
Rivka Hadar
Yair Sharav
Doron J. Aframian
Joseph Tam
Yaron Haviv
author_sort Shimrit Heiliczer
collection DOAJ
description 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.
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spelling doaj.art-c76773d0ec8a40c984eac81183736b9a2023-11-24T05:00:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211301710.3390/ijms232113017Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and ManagementShimrit Heiliczer0Asaf Wilensky1Tal Gaver2Olga Georgiev3Sharleen Hamad4Alina Nemirovski5Rivka Hadar6Yair Sharav7Doron J. Aframian8Joseph Tam9Yaron Haviv10Department of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Periodontology, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelIn Partial Fulfillment of DMD Requirements, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelIn Partial Fulfillment of DMD Requirements, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelObesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Oral Medicine, Sedation and Maxillofacial Imaging, Hadassah Medical Center, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelThe 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.https://www.mdpi.com/1422-0067/23/21/13017endocannabinoidsanandamide2-AGchronic painorofacial painneuropathic pain
spellingShingle Shimrit Heiliczer
Asaf Wilensky
Tal Gaver
Olga Georgiev
Sharleen Hamad
Alina Nemirovski
Rivka Hadar
Yair Sharav
Doron J. Aframian
Joseph Tam
Yaron Haviv
Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
International Journal of Molecular Sciences
endocannabinoids
anandamide
2-AG
chronic pain
orofacial pain
neuropathic pain
title Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
title_full Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
title_fullStr Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
title_full_unstemmed Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
title_short Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
title_sort salivary endocannabinoid profiles in chronic orofacial pain and headache disorders an observational study using a novel tool for diagnosis and management
topic endocannabinoids
anandamide
2-AG
chronic pain
orofacial pain
neuropathic pain
url https://www.mdpi.com/1422-0067/23/21/13017
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