EFFECTS OF OPIOIDS AND NON-OPIOIDS ON C-FOS-LIKE IMMUNOREACTIVITY INDUCED IN RAT LUMBAR SPINAL-CORD NEURONS BY NOXIOUS HEAT STIMULATION
EFFECTS OF OPIOIDS AND NON-OPIOIDS ON C-FOS-LIKE IMMUNOREACTIVITY INDUCED IN RAT LUMBAR SPINAL-CORD NEURONS BY NOXIOUS HEAT STIMULATION
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DOI：
10.1016/0014-2999(94)90483-9
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发表时间：
1994-06-13
影响因子：
5
通讯作者：
BESSON, JM
中科院分区：
文献类型：
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作者：
ABBADIE, C;HONORE, P;BESSON, JM
本研究评估了大鼠腰脊髓神经元在外周有害热刺激和药物诱导的改变后的 Fos 样免疫反应性。在聚氨酯麻醉下，通过将后爪浸入不同温度（44-65℃）的调节温度浴中并持续不同时间（5秒至2分钟）来刺激后爪。当爪子在 44°C 下刺激 15 秒时，腰脊髓神经元中没有出现 Fos 样免疫反应性。从46℃到52℃，Fos样免疫反应性神经元的数量随着刺激温度的升高而增加，但在65℃时与52℃相比减少。在52℃时，Fos样免疫反应性神经元的数量随着刺激时间的延长而增加。 L4 段中的 Fos 样免疫反应神经元几乎完全位于 I-II 层。根据后面实验的结果，我们选择52℃刺激15秒进行药理研究。通过吗啡预处理，热刺激诱导的 Fos 样免疫反应性神经元数量显着减少（静脉注射 2.5、5 和 7.5 mg/kg 后分别与对照值相比减少 42%、64% 和 75%），并且这些作用被纳洛酮阻断。当使用不同的刺激强度（46-52摄氏度）时，吗啡（5毫克/千克静脉注射）的效果在温度最高时最明显。在吗啡耐受大鼠中，吗啡（5 mg/kg 静脉注射）在降低热刺激诱导的 Fos 样免疫反应方面的效力是非耐受大鼠的一半。 RB 101 是一种具有全身活性的脑啡肽代谢酶混合抑制剂，可显着降低热刺激诱导的 Fos 样免疫反应性（与静脉注射 10、20 和 40 mg/kg 的对照值相比，分别降低 19%、29% 和 48%），并且这些作用可被纳洛酮阻断。阿司匹林（150 mg/kg 静脉注射）、原对乙酰氨基酚（300 mg/kg 静脉注射）和替扎尼定（一种中枢作用的肌肉松弛剂）（0.25-1 mg/kg 静脉注射）对热刺激诱导的 Fos 样免疫反应性神经元的数量没有影响。讨论了使用 c-Fos 蛋白的免疫化学作为药理学测试，以评估背角水平的抗伤害作用。
This study evaluated Fos-like immunoreactivity in rat lumbar spinal cord neurons following peripheral noxious heat stimulation and the modifications induced by pharmacological agents. Under urethane anaesthesia, the hindpaw was stimulated by dipping it in a regulated temperature bath at various temperatures (44-65 degrees C) and for various durations (5 s to 2 min). There was no Fos-like immunoreactivity in lumbar spinal cord neurons when the paw was stimulated at 44 degrees C for 15 s. From 46 to 52 degrees C, the number of Fos-like immunoreactivity neurons increased with increasing stimulation temperature, but was decreased at 65 degrees C as compared to 52 degrees C. At 52 degrees C, the number of Fos-like immunoreactivity neurons increased with the duration of stimulation. Fos-like immunoreactive neurons in the L4 segment were almost exclusively located in laminae I-II. On the basis of the results of the latter experiments, we chose a stimulation of 52 degrees C for 15 s to perform pharmacological investigations. The number of Fos-like immunoreactive neurons induced by the heat stimulation was significantly decreased by pretreatment with morphine (42, 64 and 75% decrease as compared to control values after 2.5, 5 and 7.5 mg/kg i.v. respectively), and these effects were blocked by naloxone. When various stimulation intensities (46-52 degrees C) were used, the effects of morphine (5 mg/kg i.v.) were most marked when the temperature was highest. In morphine-tolerant rats, morphine (5 mg/kg i.v.) was half as potent in decreasing Fos-like immunoreactivity induced by the heat stimulation than in non-tolerant rats. RB 101, a systemically active mixed inhibitor of enkephalin-metabolising enzymes, significantly decreased Fos-like immunoreactivity induced by heat stimulation (19, 29 and 48% decreases as compared to control values at 10, 20 and 40 mg/kg i.v. respectively) and these effects were blocked by naloxone. Aspirin (150 mg/kg i.v.), proacetaminophen (300 mg/kg i.v.) and tizanidine, a centrally acting myorelaxant (0.25-1 mg/kg i.v.), had no effect on the number of Fos-like immunoreactivity neurons induced by heat stimulation. The use of immunochemistry of the c-Fos protein as a pharmacological test in order to gauge antinociceptive effects at the dorsal horn level is discussed.