Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL^® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL^® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL^® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca²⁺ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca²⁺ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL^® are needed to sufficiently induce the therapeutic effects.

Tooth enamel is manufactured by the inner enamel epithelium of the multilayered enamel organ. Msx2 loss-of-function mutation in a mouse model causes an abnormal accumulation of epithelial cells in the enamel organ, but the underlying mechanism by which Msx2 regulates amelogenesis is poorly understood. We therefore performed detailed histological and molecular analyses of Msx2 null mice. Msx2 null ameloblasts and stratum intermedium (SI) cells differentiated normally in the early stages of amelogenesis. However, during subsequent developmental stages, the outer enamel epithelium (OEE) became highly proliferative and transformed into a keratinized stratified squamous epithelium that ectopically expressed stratified squamous epithelium markers, including Heat shock protein 25, Loricrin, and Keratin 10. Moreover, expression of hair follicle–specific keratin genes such as Keratin 26 and Keratin 73 was upregulated in the enamel organ of Msx2 mutants. With the accumulation of keratin in the stellate reticulum (SR) region and subsequent odontogenic cyst formation, SI cells gradually lost the ability to differentiate, and the expression of Sox2 and Notch1 was downregulated, leading to ameloblast depolarization. As a consequence, the organization of the Msx2 mutant enamel organ became disturbed and enamel failed to form in the normal location. Instead, there was ectopic mineralization that likely occurred within the SR. In summary, we show that during amelogenesis, Msx2 executes a bipartite function, repressing the transformation of OEE into a keratinized stratified squamous epithelium while simultaneously promoting the development of a properly differentiated enamel organ competent for enamel formation.

日本語には，「もちもち」，「カリカリ」，「シャキシャキ」などといった，食品テクスチャー（食感）を表す言葉が豊富に存在し，食感は食品のおいしさを左右する重要な要素である．また，咀嚼時には歯根膜，舌口蓋粘膜，閉口筋筋紡錘で食品テクスチャーを感知し，咀嚼力や咀嚼リズムを調節している．嚥下時には，食塊が嚥下可能なテクスチャーかどうかを判断することにより，安全な嚥下を可能にしている．このように，食品テクスチャー認知は，摂食嚥下過程においても重要な役割を担っている．しかしながら，これまでの食品テクスチャー研究は主に機器による物性測定やヒトの官能評価に依存しており，末梢でのテクスチャー刺激の受容や，認知に関わる神経回路といった生理学的メカニズムの解明は進んでいない．このように食感認知研究が進まない要因として，動物実験系を用いた食感認知の評価が困難であることが考えられる． 筆者らは，味認知の影響を排除した条件下で，ラットを用いた食品テクスチャー認知評価系の構築を試みてきた．これまでに，嫌悪および嗜好条件付け学習試験を応用することで，粘度，弾力性，硬さ，微粒子の認知が可能であることを実証しており，本総説ではこれらの実験系を紹介する．今後は，神経活動の可視化や操作と組み合わせることにより，口腔感覚情報の中枢処理メカニズムの全容解明が期待される．