Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles

Abstract Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by...

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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 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-95229-7
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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 Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.
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spelling doaj.art-634c70c42366403d96bbc0c09dd108cc2022-12-21T19:26:38ZengNature PortfolioScientific Reports2045-23222021-08-011111910.1038/s41598-021-95229-7Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter musclesAbdelrahman 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 InstitutetDepartment of Dentistry and Oral Health, Aarhus University, and 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 Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.https://doi.org/10.1038/s41598-021-95229-7
spellingShingle Abdelrahman M. Alhilou
Akiko Shimada
Camilla I. Svensson
Peter Svensson
Malin Ernberg
Brian E. Cairns
Nikolaos Christidis
Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
Scientific Reports
title Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
title_full Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
title_fullStr Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
title_full_unstemmed Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
title_short Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles
title_sort nerve growth factor and glutamate increase the density and expression of substance p containing nerve fibers in healthy human masseter muscles
url https://doi.org/10.1038/s41598-021-95229-7
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