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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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12600 |
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| 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 |
| collection | DOAJ |
| 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. |
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| language | English |
| last_indexed | 2024-03-10T05:24:40Z |
| publishDate | 2021-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5f65a1d4dceb46e6a04a5d2bb4fe4d532023-11-22T23:45:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221260010.3390/ijms222212600Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat ModelMako Naniwa0Chihiro Nakatomi1Suzuro Hitomi2Kazunari Matsuda3Takuya Tabuchi4Daijiro Sugiyama5Sayaka Kubo6Yuichi Miyamura7Kenichi Yoshino8Sumio Akifusa9Kentaro Ono10Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanDivision of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanDivision of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanR&D Department, Daiichi Sankyo Healthcare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, JapanR&D Department, Daiichi Sankyo Healthcare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, JapanR&D Department, Daiichi Sankyo Healthcare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, JapanR&D Department, Daiichi Sankyo Healthcare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, JapanDivision of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanSection of Primary Dental Education, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanSchool of Oral Health Sciences, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanDivision of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Fukuoka, JapanDespite 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.https://www.mdpi.com/1422-0067/22/22/12600stomatitistriamcinolone acetonideglucocorticoidspainorofacial paintrigeminal ganglion |
| spellingShingle | 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 International Journal of Molecular Sciences stomatitis triamcinolone acetonide glucocorticoids pain orofacial pain trigeminal ganglion |
| title | 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_short | 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 |
| topic | stomatitis triamcinolone acetonide glucocorticoids pain orofacial pain trigeminal ganglion |
| url | https://www.mdpi.com/1422-0067/22/22/12600 |
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