Anesthetic mechanisms and surgical injury

麻醉机制和手术损伤

• 批准号: 13470325
• 负责人: NAMIKI Akiyoshi
• 金额: $ 8.51万
• 依托单位: Sapporo Med.Univ.Sch.of Med.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470325/
• 关键词: anesthetics; surgical injury; spinal cord dorsal horn; hyperalgesia; 術後痛; パッチクランプ; in vivo; 皮膚切開; in vivoパッチクランプ; 脊髄後角膠様質ニューロン; 脊髄; パッチクランプ法

Background : Since volatile anesthetics are capable of blocking sensory transmission, including pain sensation, at the level of the spinal dorsal horn(SDH), they could suppress incision-induced excitation during surgery and hence prevent or attenuate central sensitization of SDH neurons after surgery. In spite of this possibility, volatile anesthetics are generally considered to have little or no effects on central sensitization after surgery. The aim of this study was to determine whether halothane and isoflurane used during surgery can suppress or attenuate hyperexcitability of SDH neurons after an incision in the rat.Methods : Activity of a single SDH wide-dynamic-range(WDR) neuron that had a receptive field(RF) on hairy skin of the hindquarter was isolated in decerebrate-spinal Sprague-Drawley rats, and neuronal activity(RF size and responses to non-noxious and noxious stimuli) was recorded. A l-cm-Long incision was made through the skin, fascia and muscle in the center of the RF u … More nder anesthesia with halothane(1.1% or 2.2%) and isoflurane(1.4% or 2.8%). Anesthesia was discontinued just after the incision had been made or was continued until 30min after the incision had been made, and activity of SDH neurons was measured for up to 2 hrs after the incision had been made. Data were compared with those obtained from control animals(control group) in which the incision was made without anesthesia.Results : In the control group, the incision resulted in maximum excitation in the SDH neurons during surgery ; spontaneous activity significantly increased for up to 30min after the incision had been made(P<0.05) but did not significantly increase thereafter, returning to pre-incision levels. Halothane and isoflurane suppressed excitation of SDH neurons during the incision in a concentration-related manner. Administration of 2.2% halothane and 2.8% isoflurane during the incision and for up to 30min after the incision had been made abolished spontaneous activity of SDH neurons. for 30min after the incision had been made. The magnitude of the responses to the stimuli and expanded RF sizes were not significantly different in each anesthesia group compared to those in the control group. There were no significant relations between excitation during the incision and RF expansion after the incision or between the increase in spontaneous activity and RF expansion after the incision.Conclusions : These results demonstrate that administration of halothane and isoflurane does not attenuate or prevent development of hyperexcitability of SDH neurons despite the fact that excitation of SDH neurons during the incision and spontaneous activity after the incision were greatly suppressed by administration of halothane and isoflurane, suggesting that central mechanisms are less involved in occurrence of incision-induced pain state than peripheral mechanisms. Less

背景资料：由于挥发性麻醉药能够阻断脊髓背角（SDH）水平的感觉传递，包括痛觉，因此它们可以抑制手术期间切口诱导的兴奋，从而防止或减弱手术后SDH神经元的中枢敏化。尽管存在这种可能性，但一般认为挥发性麻醉剂对术后中枢致敏作用很小或没有作用。本研究的目的是确定手术期间使用的氟烷和异氟烷是否可以抑制或减弱大鼠切口后SDH神经元的过度兴奋。在去大脑脊髓的Sprague-Drawley大鼠中分离出在后躯有毛皮肤上具有感受野（RF）的单个SDH宽动态范围（WDR）神经元的活性，并记录神经元活动（RF大小和对非伤害性和伤害性刺激的反应）。在射频消融中心作一个1cm长的皮肤、筋膜和肌肉切口， ...更多信息 氟烷（1.1%或2.2%）和异氟醚（1.4%或2.8%）麻醉。在切开后立即停止麻醉或继续麻醉至切开后30 min，并在切开后2 h内测量SDH神经元的活性。结果：在对照组中，手术中切口导致SDH神经元的最大兴奋，在切口后30 min内自发活动显著增加（P<0.05），但此后没有显著增加，恢复到切口前水平。氟烷和异氟醚抑制SDH神经元的兴奋在切口中的浓度相关的方式。术中及术后30 min给予2.2%氟烷和2.8%异氟醚可抑制SDH神经元的自发活动。切开后30 min内，与对照组相比，各麻醉组对刺激和扩大RF大小的反应幅度无显著差异。切开期间的兴奋与切开后的RF扩张之间或切开后的自发活动增加与RF扩张之间没有显著关系。这些结果表明，氟烷和异氟烷的给药不能减弱或防止SDH神经元的过度兴奋性的发展，尽管事实上在切口期间SDH神经元的兴奋和切口后的自发活动氟烷和异氟烷的给药极大地抑制了，表明中枢机制比外周机制更少地参与切口诱导的疼痛状态的发生。少

项目成果

Kawamata M et al.: "Effects of halothane and isoflurane on hHyperexcitability of spinal dorsal horn neurons after incision in the rat"Anesthesiology. (in press). (2004)

Kawamata M 等人：“氟烷和异氟烷对大鼠切口后脊髓背角神经元超兴奋性的影响”麻醉学。

Koshizaki M, Kawamata M, Shimada SG, Saito Y, Collins JG: "5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons."Anesth Analg. 96(4). 1027-1031 (2003)

Koshizaki M、Kawamata M、Shimada SG、Saito Y、Collins JG：“5-HT3 受体部分介导脊髓背角感觉神经元的氟烷抑制。”Anesth Analg。

Kamada Y, Yamada Y, Yamakage M, Nagashima M, Tsutsuura M, Kobayashi T, Seki S, Namiki A, Tohse N.: "Single-channel activity of L-type Ca(2+) channels reconstituted with the beta(2c) subunit cloned from the rat heart."Eur J Pharmacol. 487(1-3). 37-45 (2004

Kamada Y、Yamada Y、Yamakage M、Nagashima M、Tsutsuura M、Kobayashi T、Seki S、Namiki A、Tohse N.：“用 beta(2c) 亚基重构的 L 型 Ca(2) 通道的单通道活性

Koshizaki M, Kawamata M, Shimada SG, Saito Y, Colins JG.: "5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons."Anesth Analg. 96(4). 1027-1031 (2003)

Koshizaki M、Kawamata M、Shimada SG、Saito Y、Colins JG.：“5-HT3 受体部分介导脊髓背角感觉神经元的氟烷抑制。”Anesth Analg。

Kawamata M et al.: "Differential mechanisms of development and maintenance of experimental incision-induced hyperalgesia in human skin"Anesthesiology. 97. 550-559 (2002)

Kawamata M 等人：“人类皮肤中实验性切口诱导的痛觉过敏的发展和维持的不同机制”麻醉学。