Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice

• Material Type: 博士論文
• Title: Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice
• Author/Editor: Matsuda, Keiichiro
• Author Heading: Matsuda, Keiichiro
• Publication Date: 2022-09-20
• Publication Date (W3CDTF): 2022-09-20
• Alternative Title: 術後疼痛モデルマウスにおけるデキサメタゾン添加坐骨神経ブロックの鎮痛効果の延長は神経型一酸化窒素合成酵素の抑制によりもたらされる
• Degree grantor/type: 新潟大学
• Date Granted: 2022-09-20
• Date Granted (W3CDTF): 2022-09-20
• Dissertation Number: 甲第5075号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Alias of Author: 松田, 敬一郎
• Subject Heading: Dexamethasone; local anesthetic; nitric oxide synthase; prolonged analgesic effect; nerve block
• Target Audience: 一般
• Note (General): Abstract: Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. Dexamethasone supplementation to ropivacaine significantly prolonged the analgesic effect of SNB via glucocorticoid receptor activation. Histological examination revealed that ropivacaine suppressed p-p38 MAPK expression in the DRG regardless of dexamethasone supplementation, suggesting that p-p38 MAPK was not involved in the prolonging effect of dexamethasone on nerve block. Contrastingly, plantar incision markedly increased the expression of neuronal NOS (nNOS) in DRG, and dexamethasone supplementation to ropivacaine significantly suppressed nNOS expression. Supplementation of L-NAME, an inhibitor of NOS, to ropivacaine markedly prolonged the effect of SNB, similar to dexamethasone. These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. Perspective: The current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.; The Journal of Pain. 2022, 23(10), 1765-1778.; 新大院博(医)第1088号
• Persistent ID (NDL): info:ndljp/pid/12864334; https://dl.ndl.go.jp/pid/12864334
• Collection: 障害者向け資料
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-05-05T22:12:36+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://hdl.handle.net/10191/0002000967; https://niigata-u.repo.nii.ac.jp/records/2000967
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp