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Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity
Daisuke Ikutame1, Kentaro Urata1, Tatsuki Oto1
1Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
Abstract:
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.
Insights
Aging accelerates orofacial pain hypersensitivity by promoting pro-inflammatory microglia (M1) and reducing anti-inflammatory microglia (M2). This study used senescence-accelerated mice to investigate age-related changes in microglia polarization and intraoral pain.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Microglia, the immune cells of the central nervous system, exhibit distinct polarization states (M1 and M2) crucial for regulating pain.
- Orofacial pain hypersensitivity is linked to activated microglia, with aging potentially exacerbating this response through altered microglial phenotypes.
Purpose of the Study:
- To investigate the role of aging-related phenotypic conversion of medullary microglia in enhancing intraoral pain sensitivity.
- To compare microglia activation and polarization in aging (SAMP8) versus control (SAMR1) mice following palatal mucosal incision.
Main Methods:
- Mechanical head-withdrawal threshold (MHWT) was measured in senescence-accelerated mice (SAMP8) and resistant controls (SAMR1) for 21 days post-incision.
- Immunohistochemistry was used to quantify CD11c (M1) and CD163 (M2) positive microglia, as well as tumor-necrosis-factor-α (TNF-α) and interleukin-10 (IL-10) expression on days 3 and 11.
Main Results:
- SAMP8 mice exhibited a greater decrease in MHWT, indicating enhanced mechanical allodynia after injury.
- Increased M1 levels and TNF-α expression were observed on day 3 in SAMP8 mice.
- On day 11, while both M1 and M2 were activated, SAMP8 mice showed attenuated IL-10 levels and sustained M1 activation with higher TNF-α.
Conclusions:
- Aging potentiates and prolongs mechanical allodynia following intraoral injury in SAMP8 mice.
- This potentiation is associated with enhanced TNF-α signaling, M1 activation, and reduced M2 activation with diminished IL-10 release.
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