Suzukawa M, Matsumoto M, Collins J G, Kitahata L M, Yuge O
Anesthesiology. 1983 Jun;58(6):510-3. doi: 10.1097/00000542-198306000-00005.
The present study examined the influence of spinally administered fentanyl on the spontaneous and noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of decerebrate, spinal cord-transected cats. This work was performed in order to evaluate the dose-response relationship, time course, and naloxone reversibility of fentanyl suppression of neurons that are involved with the transmission of information about pain. Extracellular single neuron recordings were obtained from 18 WDR neurons in the lumbar enlargement. These neurons were activated by a radiant heat stimulus on the footpads of the hindpaw. Fentanyl (10, 15, 25 micrograms in 0.5 ml of physiologic saline) was placed on the spinal cord following control studies of each neuron and the effect was observed. In 12 cats, 31 min after fentanyl administration, naloxone (0.1 mg) was administered intravenously, and its effect on the fentanyl suppression was determined. All three doses of fentanyl suppressed both the spontaneous and evoked activity of all the neurons studied. Thirty minutes after fentanyl the mean evoked activity was reduced to 47, 23, and 11% of control values by 10, 15, and 25 micrograms, respectively. The spontaneous activity was reduced to similar levels. Intravenous naloxone (0.1 mg) caused a significant reversal of the fentanyl suppression. The results of the present study indicate that fentanyl causes a naloxone-reversible, dose-dependent suppression of noxiously evoked WDR neuron activity. Such results support the concept that fentanyl is acting through a specific drug-receptor interaction. The onset of neuronal suppression occurred more rapidly, and the duration of the suppression was longer following fentanyl than that seen following spinal morphine. The onset and duration of this suppression correlates well with human clinical data, providing further evidence that alterations of WDR neuronal activity may be important in the production of spinal opioid analgesia.
本研究检测了脊髓注射芬太尼对去大脑、脊髓横断猫的背角广动力范围（WDR）神经元的自发活动和伤害性诱发活动的影响。开展这项工作是为了评估芬太尼对参与疼痛信息传递的神经元抑制作用的剂量-反应关系、时间进程和纳洛酮可逆性。从腰膨大处的18个WDR神经元进行了细胞外单神经元记录。这些神经元通过后爪脚垫上的热辐射刺激激活。在对每个神经元进行对照研究后，将芬太尼（10、15、25微克溶于0.5毫升生理盐水中）注入脊髓，并观察其效果。在12只猫中，芬太尼给药31分钟后，静脉注射纳洛酮（0.1毫克），并确定其对芬太尼抑制作用的影响。所有三种剂量的芬太尼均抑制了所有研究神经元的自发活动和诱发活动。芬太尼给药30分钟后，10、15和25微克芬太尼分别使平均诱发活动降至对照值的47%、23%和11%。自发活动也降至相似水平。静脉注射纳洛酮（0.1毫克）导致芬太尼抑制作用显著逆转。本研究结果表明，芬太尼可引起纳洛酮可逆的、剂量依赖性的伤害性诱发WDR神经元活动抑制。这些结果支持了芬太尼通过特定药物-受体相互作用发挥作用的概念。与脊髓注射吗啡相比，芬太尼引起神经元抑制的起效更快，抑制持续时间更长。这种抑制的起效和持续时间与人类临床数据相关性良好，进一步证明WDR神经元活动的改变可能在脊髓阿片类镇痛的产生中起重要作用。
