Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants

Abstract The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of sub...

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Main Authors: Abdelrahman M. Alhilou, Akiko Shimada, Camilla I. Svensson, Peter Svensson, Malin Ernberg, Brian E. Cairns, Nikolaos Christidis
Format: Article
Language:English
Published: Nature Portfolio 2021-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-93171-2
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author Abdelrahman M. Alhilou
Akiko Shimada
Camilla I. Svensson
Peter Svensson
Malin Ernberg
Brian E. Cairns
Nikolaos Christidis
author_facet Abdelrahman M. Alhilou
Akiko Shimada
Camilla I. Svensson
Peter Svensson
Malin Ernberg
Brian E. Cairns
Nikolaos Christidis
author_sort Abdelrahman M. Alhilou
collection DOAJ
description Abstract The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P < 0.050). Significant positive correlations were found between nerve fiber expression of NMDA-receptors and peak pain intensity (rs = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = − 0.659, P = 0.013), and in combination with NGF (rs = − 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.
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spelling doaj.art-3ad27e6f08df4f04bb27d76dd357d1ca2022-12-21T23:10:41ZengNature PortfolioScientific Reports2045-23222021-07-0111111210.1038/s41598-021-93171-2Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participantsAbdelrahman M. Alhilou0Akiko Shimada1Camilla I. Svensson2Peter Svensson3Malin Ernberg4Brian E. Cairns5Nikolaos Christidis6Department of Restorative Dentistry, College of Dentistry, Umm Al-Qura UniversityDepartment of Geriatric Dentistry, Osaka Dental UniversityDepartment of Physiology and Pharmacology, Center for Molecular Medicine, Karolinska InstitutetSection of Orofacial Pain and Jaw Function, Department of Dentistry and Oral Health, Aarhus University, and Scandinavian Center for Orofacial Neurosciences (SCON)Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, and Scandinavian Center for Orofacial Neurosciences (SCON)Faculty of Pharmaceutical Sciences, University of British ColumbiaDivision of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, and Scandinavian Center for Orofacial Neurosciences (SCON)Abstract The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P < 0.050). Significant positive correlations were found between nerve fiber expression of NMDA-receptors and peak pain intensity (rs = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = − 0.659, P = 0.013), and in combination with NGF (rs = − 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.https://doi.org/10.1038/s41598-021-93171-2
spellingShingle Abdelrahman M. Alhilou
Akiko Shimada
Camilla I. Svensson
Peter Svensson
Malin Ernberg
Brian E. Cairns
Nikolaos Christidis
Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
Scientific Reports
title Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
title_full Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
title_fullStr Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
title_full_unstemmed Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
title_short Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
title_sort sex related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
url https://doi.org/10.1038/s41598-021-93171-2
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