Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury

Abstract

Background/Aim: The ectopic pain associated with inferior alveolar nerve (IAN) injury has been reported to involve macrophage expression in the trigeminal ganglion (TG). However, the effect of age-related changes on this abnormal pain conditions are still unknown. This study sought to clarify the involvement of age-related changes in macrophage expression and phenotypic conversion in the TG and how these changes enhance ectopic mechanical allodynia after IAN transection (IANX). Materials and Methods: We used senescence-accelerated mouse (SAM)-prone 8 (SAMP8) and SAM-resistance 1 (SAMR1) mice, which are commonly used to study ageing-related changes. Mechanical stimulation was applied to the whisker pad skin under light anaesthesia; the mechanical head withdrawal threshold (MHWT) was measured for 21 d post-IANX. We subsequently counted the numbers of Iba1 (macrophage marker)-immunoreactive (IR) cells, Iba1/CD11c (M1-like inflammatory macrophage marker)-co-IR cells, and Iba1/CD206 (M2-like anti-inflammatory macrophage marker)-co-IR cells in the TG innervating the whisker pad skin. After continuous intra-TG administration of liposomal clodronate Clophosome® -A (LCCA) to IANX-treated SAMP8mice, the MHWT values of the whisker pad skin were examined. Results: Five days post-IANX, the MHWT had significantly decreased in SAMP8 mice compared to SAMR1-mice. Iba1-IR and Iba1/CD11c-co-IR cell counts were significantly increased in SAMP8 mice compared to SAMR1 mice 5 d post-IANX. LCCA administration significantly restored MHWT compared to control-LCCA administration. Conclusion: Ectopic mechanical allodynia of whisker pad skin after IANX is exacerbated by ageing, which involves increases in M1-like inflammatory macrophages in the TG.

Exploring the Connectivity of Neurodegenerative Diseases: Microglia as the Center

“… 6 Some degenerative diseases are peripheral neurodegenerative diseases, such as pain neuron degeneration and osteoarthritis. 7 , 8 Although many studies are conducted on degenerative diseases, few study has explored the underlying commonality of these degenerative diseases. Therefore, exploring the commonality of central and peripheral mechanisms is vital in finding novel treatments, which is the objective of this review.…”

Remodeling of Blood Vessels by Binge Alcohol Intake in the Mouse Trigeminal Ganglia

“…19,20) IBA1/AIF1, however, is also expressed in macrophages in the periphery, therefore the exact cell type of the IBA1/AIF1-positive population in the trigeminal ganglia is still in debate. 21,22) We refer to these IBA1/ AIF1-positive cells in the trigeminal ganglia as "microglialike cells" in this manuscript. These microglia-like cells in the trigeminal ganglia may be responsible for the modulation of sensory signal transmission.…”

“…These microglia-like cells in the trigeminal ganglia may be responsible for the modulation of sensory signal transmission. 21,22) To unveil the pathological effects and mechanisms of ethanol toxicity, our investigation has explored the impact of excess ethanol intake on the nervous system, revealing blood vessel remodeling in the mouse cerebral cortex. 23) However, it remains uncertain whether blood vessels in other nervous system regions undergo similar remodeling due to excess ethanol intake.…”