DEXMEDETOMIDINE PROLONGS LEVOBUPIVACAINE ANALGESIA VIA INHIBITION OF INFLAMMATION AND p38 MAPK PHOSPHORYLATION IN RAT DORSAL ROOT GANGLION
DEXMEDETOMIDINE PROLONGS LEVOBUPIVACAINE ANALGESIA VIA INHIBITION OF INFLAMMATION AND p38 MAPK PHOSPHORYLATION IN RAT DORSAL ROOT GANGLION
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DOI：
10.1016/j.neuroscience.2017.08.011
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发表时间：
2017-10-11
期刊：
影响因子：
3.3
通讯作者：
Amaya, Fumimasa
中科院分区：
文献类型：
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作者：
Yamakita, Shunsuke;Matsuda, Megumi;Amaya, Fumimasa
组织损伤后，初级传入神经元中 p38 MAPK 的磷酸化驱动周围神经的敏化。右美托咪定可延长局部麻醉药的区域镇痛持续时间。局部镇痛对周围神经敏化的影响尚不清楚。本研究旨在探讨左布比卡因联合或不联合右美托咪定局部镇痛对背根神经节（DRG）p38 MAPK磷酸化及周围组织炎症反应的影响。在 Sprague-Dawley 大鼠的后爪上切开足底切口。切开之前，将左布比卡因联合或不联合右美托咪定注射到爪子和脚踝的足底。进行了一项行为研究来调查疼痛过敏。通过免疫组织化学和蛋白质印迹评估 DRG 中 p38 MAPK 的磷酸化。使用免疫组织化学、实时 PCR 和 ELISA 测量 DRG 和足底组织中的巨噬细胞积累、NGF 和 TNF-α。足底切口后立即诱发疼痛过敏。左布比卡因治疗可抑制疼痛过敏的发生两小时。辅助右美托咪定将抗痛觉过敏持续时间延长四个小时。没有右美托咪定的左布比卡因不能完全抑制 DRG 中的 p38 MAPK 磷酸化。然而，左布比卡因和右美托咪定完全抑制p38 MAPK磷酸化，并减少足底组织中巨噬细胞的积累和TNF-α的量。通过 TNF-a 抑制 p38 MAPK 磷酸化表明右美托咪定在用作局麻药辅助剂时具有外周抗炎作用机制，并为预防手术后外周致敏提供了分子基础。 (C) 2017 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Following tissue injury, phosphorylation of p38 MAPK in the primary afferent neurons drives sensitization of peripheral nerve. Dexmedetomidine extends the duration of reginal analgesia by local anesthetics. The effect of regional analgesia on the peripheral nerve sensitization is not known. The aim of this study is to investigate the effect of regional analgesia by levobupivacaine with or without dexmedetomidine on the p38 MAPK phosphorylation in the dorsal root ganglion (DRG) and inflammatory reaction in the peripheral tissue. A plantar incision was made in the hind paws of Sprague-Dawley rats. Prior to incision, levobupivacaine with or without dexmedetomidine was injected to the plantar aspect of the paws and ankles. A behavioral study was performed to investigate pain hypersensitivity. Phosphorylation of p38 MAPK in the DRG was assessed by immunohistochemistry and Western blotting. Macrophage accumulation, NGF, and TNF-alpha in the DRG and plantar tissue were measured using immunohistochemistry, real-time PCR and ELISA. Pain hypersensitivity was induced immediately after the plantar incision. Treatment with levobupivacaine inhibited the development of pain hypersensitivity for two hours. Adjunctive dexmedetomidine extended the anti-hyperalgesic duration for four hours. Levobupivacaine without dexmedetomidine could not inhibit p38 MAPK phosphorylation in the DRG completely. However, Levobupivacaine and dexmedetomidine completely inhibited p38 MAPK phosphorylation, and reduced macrophage accumulation and TNF-a amount in the plantar tissue. Inhibition of p38 MAPK phosphorylation via TNF-a suggests dexmedetomidine has a peripheral mechanism of anti-inflammatory action when used as an adjunct to local anesthetics, and provides a molecular basis for the prevention of peripheral sensitization following surgery. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.