Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity

Activated microglia involved in the development of orofacial pain hypersensitivity have two major polarization states. The aim of this study was to assess the involvement of the aging-related phenotypic conversion of medullary microglia in the enhancement of intraoral pain sensitivity using senescen...

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Main Authors: Daisuke Ikutame, Kentaro Urata, Tatsuki Oto, Shintaro Fujiwara, Toshimitsu Iinuma, Ikuko Shibuta, Yoshinori Hayashi, Suzuro Hitomi, Koichi Iwata, Masamichi Shinoda
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/21/21/7871
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author Daisuke Ikutame
Kentaro Urata
Tatsuki Oto
Shintaro Fujiwara
Toshimitsu Iinuma
Ikuko Shibuta
Yoshinori Hayashi
Suzuro Hitomi
Koichi Iwata
Masamichi Shinoda
author_facet Daisuke Ikutame
Kentaro Urata
Tatsuki Oto
Shintaro Fujiwara
Toshimitsu Iinuma
Ikuko Shibuta
Yoshinori Hayashi
Suzuro Hitomi
Koichi Iwata
Masamichi Shinoda
author_sort Daisuke Ikutame
collection DOAJ
description Activated microglia involved in the development of orofacial pain hypersensitivity have two major polarization states. The aim of this study was to assess the involvement of the aging-related phenotypic conversion of medullary microglia in the enhancement of intraoral pain sensitivity using senescence-accelerated mice (SAM)-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) mice. Mechanical head-withdrawal threshold (MHWT) was measured for 21 days post palatal mucosal incision. The number of CD11c-immunoreactive (IR) cells [affective microglia (M1)] and CD163-IR cells [protective microglia (M2)], and tumor-necrosis-factor-α (TNF-α)-IR M1 and interleukin (IL)-10-IR M2 were analyzed via immunohistochemistry on days 3 and 11 following incision. The decrease in MHWT observed following incision was enhanced in SAMP8 mice. M1 levels and the number of TNF-α-IR M1 were increased on day 3 in SAMP8 mice compared with those in SAMR1 mice. On day 11, M1 and M2 activation was observed in both groups, whereas IL-10-IR M2 levels were attenuated in SAMP8 mice, and the number of TNF-α-IR M1 cells increased, compared to those in SAMR1 mice. These results suggest that the mechanical allodynia observed following intraoral injury is potentiated and sustained in SAMP8 mice due to enhancement of TNF-α signaling, M1 activation, and an attenuation of M2 activation accompanying IL-10 release.
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spelling doaj.art-4f6a6ea814564c83b5a093e4180334c42023-11-20T18:19:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121787110.3390/ijms21217871Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain SensitivityDaisuke Ikutame0Kentaro Urata1Tatsuki Oto2Shintaro Fujiwara3Toshimitsu Iinuma4Ikuko Shibuta5Yoshinori Hayashi6Suzuro Hitomi7Koichi Iwata8Masamichi Shinoda9Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, JapanDepartment of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, JapanActivated microglia involved in the development of orofacial pain hypersensitivity have two major polarization states. The aim of this study was to assess the involvement of the aging-related phenotypic conversion of medullary microglia in the enhancement of intraoral pain sensitivity using senescence-accelerated mice (SAM)-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) mice. Mechanical head-withdrawal threshold (MHWT) was measured for 21 days post palatal mucosal incision. The number of CD11c-immunoreactive (IR) cells [affective microglia (M1)] and CD163-IR cells [protective microglia (M2)], and tumor-necrosis-factor-α (TNF-α)-IR M1 and interleukin (IL)-10-IR M2 were analyzed via immunohistochemistry on days 3 and 11 following incision. The decrease in MHWT observed following incision was enhanced in SAMP8 mice. M1 levels and the number of TNF-α-IR M1 were increased on day 3 in SAMP8 mice compared with those in SAMR1 mice. On day 11, M1 and M2 activation was observed in both groups, whereas IL-10-IR M2 levels were attenuated in SAMP8 mice, and the number of TNF-α-IR M1 cells increased, compared to those in SAMR1 mice. These results suggest that the mechanical allodynia observed following intraoral injury is potentiated and sustained in SAMP8 mice due to enhancement of TNF-α signaling, M1 activation, and an attenuation of M2 activation accompanying IL-10 release.https://www.mdpi.com/1422-0067/21/21/7871microgliaM1M2senescence-accelerated miceSAMP8SAMR1
spellingShingle Daisuke Ikutame
Kentaro Urata
Tatsuki Oto
Shintaro Fujiwara
Toshimitsu Iinuma
Ikuko Shibuta
Yoshinori Hayashi
Suzuro Hitomi
Koichi Iwata
Masamichi Shinoda
Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
International Journal of Molecular Sciences
microglia
M1
M2
senescence-accelerated mice
SAMP8
SAMR1
title Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
title_full Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
title_fullStr Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
title_full_unstemmed Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
title_short Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
title_sort aging related phenotypic conversion of medullary microglia enhances intraoral incisional pain sensitivity
topic microglia
M1
M2
senescence-accelerated mice
SAMP8
SAMR1
url https://www.mdpi.com/1422-0067/21/21/7871
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