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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-10-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/21/7871 |
_version_ | 1797549970016960512 |
---|---|
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. |
first_indexed | 2024-03-10T15:22:35Z |
format | Article |
id | doaj.art-4f6a6ea814564c83b5a093e4180334c4 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T15:22:35Z |
publishDate | 2020-10-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT daisukeikutame agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT kentarourata agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT tatsukioto agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT shintarofujiwara agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT toshimitsuiinuma agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT ikukoshibuta agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT yoshinorihayashi agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT suzurohitomi agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT koichiiwata agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity AT masamichishinoda agingrelatedphenotypicconversionofmedullarymicrogliaenhancesintraoralincisionalpainsensitivity |