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The mechanism of neuropathic pain in rats that had undergone left L5 spinal nerve transection was analyzed. Ten days after surgery, these rats acquired neuropathic pain. The patch-clamp technique was used on the isolated bilateral L5 dorsal root ganglion neurons. The current-clamped neurons on the ipsilateral side exhibited significantly higher excitability than those on the contralateral side. However, only neurons with diameters of 40-50 mu m on the ipsilateral side exhibited significantly larger voltage sags in response to hyperpolarizing current pulses than those on the contralateral side. Under the voltage clamp, only these neurons on the ipsilateral side showed a significantly larger density of an inward current at \u003c -80 mV [hyperpolarization-activated nonselective cation (I-h) current] with a rightward-shifted activation curve than that on the contralateral side. Ivabradine-an I-h current inhibitor-inhibited I-h currents in these neurons on both sides in a similar concentration-dependent manner, with an IC50 value of similar to 3 mu M. Moreover, the oral administration of ivabradine significantly alleviated the neuropathic pain on the ipsilateral side. An inhibitor of adenylyl cyclase or an antagonist of prostanoid EP4 receptors (CJ-023423) inhibited ipsilateral, but not contralateral I-h, currents in these neurons. Furthermore, the intrathecal administration of CJ-023423 significantly attenuated neuropathic pain on the ipsilateral side. Thus, ivabradine and/or CJ-023423 may be a lead compound for the development of novel therapeutics against neuropathic pain."}]}, "item_1627890986942": {"attribute_name": "\u51fa\u7248\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u5f35, \u660a"}], "nameIdentifiers": [{"nameIdentifier": "108082", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "14MH081B_yoshi.pdf", "filesize": [{"value": "156.1 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 156100.0, "url": {"label": "\u5185\u5bb9\u306e\u8981\u65e8", "url": "https://soar-ir.repo.nii.ac.jp/record/20746/files/14MH081B_yoshi.pdf"}, "version_id": "023027ec-3c59-4b45-945a-bf072e92a1ea"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "14MH081B_shinsa.pdf", "filesize": [{"value": "142.3 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 142300.0, "url": {"label": "\u5be9\u67fb\u7d50\u679c\u306e\u8981\u65e8", "url": "https://soar-ir.repo.nii.ac.jp/record/20746/files/14MH081B_shinsa.pdf"}, "version_id": "db6a6374-61e4-4ef5-8b6d-c2d53b4b46b1"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-06-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "14MH081B_ronbun.pdf", "filesize": [{"value": "928.5 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "\u00a9 2018 by The American Society for Pharmacology and Experimental Therapeutics / Reprinted with permission of the American Society for Pharmacology and Experimental Therapeutics. 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Prostanoid EP4 receptor-mediated augmentation of Ih currents in Aβ dorsal root ganglion neurons underlies neuropathic pain(プロスタノイドEP4受容体を介したAβ後根神経節細胞のIh電流増大が神経障害性疼痛を引き起こす)
http://hdl.handle.net/10091/00021504
00788f06-b772-478d-9f37-04345736bfd6
名前 / ファイル | ライセンス | アクション | |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2019-06-14 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Prostanoid EP4 receptor-mediated augmentation of Ih currents in Aβ dorsal root ganglion neurons underlies neuropathic pain(プロスタノイドEP4受容体を介したAβ後根神経節細胞のIh電流増大が神経障害性疼痛を引き起こす) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
著者 |
張, 昊
× 張, 昊 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 張 昊. Prostanoid EP4 receptor-mediated augmentation of Ih currents in Aβ dorsal root ganglion neurons underlies neuropathic pain(プロスタノイドEP4受容体を介したAβ後根神経節細胞のIh電流増大が神経障害性疼痛を引き起こす). 信州大学, 2018, 博士論文. | |||||
書誌情報 |
発行日 2018-09-30 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1163号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2018-09-30 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | ||||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
Doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1163号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 368(1):50-58 (2019); doi:10.1124/jpet.118.252767. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
関連識別子 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=30409832 | |||||
関連名称 | ||||||
関連名称 | 30409832 | |||||
DOI | ||||||
関連識別子 | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1124/jpet.118.252767 | |||||
関連名称 | ||||||
関連名称 | 10.1124/jpet.118.252767 | |||||
権利 | ||||||
権利情報 | © 2018 by The American Society for Pharmacology and Experimental Therapeutics / Reprinted with permission of the American Society for Pharmacology and Experimental Therapeutics. All rights reserved. | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000457849600006 |