Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model

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 o...

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Autores principales:	Mako Naniwa, Chihiro Nakatomi, Suzuro Hitomi, Kazunari Matsuda, Takuya Tabuchi, Daijiro Sugiyama, Sayaka Kubo, Yuichi Miyamura, Kenichi Yoshino, Sumio Akifusa, Kentaro Ono
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	stomatitis triamcinolone acetonide glucocorticoids pain orofacial pain trigeminal ganglion Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5f65a1d4dceb46e6a04a5d2bb4fe4d53
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spelling	oai:doaj.org-article:5f65a1d4dceb46e6a04a5d2bb4fe4d532021-11-25T17:58:17ZAnalgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model10.3390/ijms2222126001422-00671661-6596https://doaj.org/article/5f65a1d4dceb46e6a04a5d2bb4fe4d532021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12600https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Despite 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<sup>®</sup> ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL<sup>®</sup> 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<sup>®</sup> with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca<sup>2+</sup> imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca<sup>2+</sup> 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<sup>®</sup> are needed to sufficiently induce the therapeutic effects.Mako NaniwaChihiro NakatomiSuzuro HitomiKazunari MatsudaTakuya TabuchiDaijiro SugiyamaSayaka KuboYuichi MiyamuraKenichi YoshinoSumio AkifusaKentaro OnoMDPI AGarticlestomatitistriamcinolone acetonideglucocorticoidspainorofacial paintrigeminal ganglionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12600, p 12600 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	stomatitis triamcinolone acetonide glucocorticoids pain orofacial pain trigeminal ganglion Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	stomatitis triamcinolone acetonide glucocorticoids pain orofacial pain trigeminal ganglion Biology (General) QH301-705.5 Chemistry QD1-999 Mako Naniwa Chihiro Nakatomi Suzuro Hitomi Kazunari Matsuda Takuya Tabuchi Daijiro Sugiyama Sayaka Kubo Yuichi Miyamura Kenichi Yoshino Sumio Akifusa Kentaro Ono Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
description	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<sup>®</sup> ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL<sup>®</sup> 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<sup>®</sup> with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca<sup>2+</sup> imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca<sup>2+</sup> 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<sup>®</sup> are needed to sufficiently induce the therapeutic effects.
format	article
author	Mako Naniwa Chihiro Nakatomi Suzuro Hitomi Kazunari Matsuda Takuya Tabuchi Daijiro Sugiyama Sayaka Kubo Yuichi Miyamura Kenichi Yoshino Sumio Akifusa Kentaro Ono
author_facet	Mako Naniwa Chihiro Nakatomi Suzuro Hitomi Kazunari Matsuda Takuya Tabuchi Daijiro Sugiyama Sayaka Kubo Yuichi Miyamura Kenichi Yoshino Sumio Akifusa Kentaro Ono
author_sort	Mako Naniwa
title	Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
title_short	Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
title_full	Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
title_fullStr	Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
title_full_unstemmed	Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model
title_sort	analgesic mechanisms of steroid ointment against oral ulcerative mucositis in a rat model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5f65a1d4dceb46e6a04a5d2bb4fe4d53
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Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model

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