足底注射吗啡可抑制角叉菜胶炎症诱导的脊髓c-Fos表达，但对热刺激诱导的表达无抑制作用。

Intraplantar morphine depresses spinal c-Fos expression induced by carrageenin inflammation but not by noxious heat.

作者信息

Honoré P, Buritova J, Besson J M

机构信息

Physiopharmacologie du Système Nerveux, INSERM U.161, Paris, France.

出版信息

Br J Pharmacol. 1996 Jun;118(3):671-80. doi: 10.1111/j.1476-5381.1996.tb15453.x.

DOI:10.1111/j.1476-5381.1996.tb15453.x

PMID:8762093

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909746/

Abstract

We have studied the effects of intraplantar administration of the same doses of morphine on intraplantar carrageenin (6 mg 150 microliters-1 of saline) and noxious heat (52 degrees C for 15 s) induced spinal c-Fos expression and inflammation. 2. Intraplantar carrageenin, in awake rats, induced numerous Fos-like immunoreactive (Fos-LI) neurones in the dorsal horn of L4-L5 lumbar segments of the spinal cord and extensive peripheral oedema. At 1 h 30 min, Fos-LI neurones were preferentially located in the superficial laminae (74 +/- 2%) whereas at 3 h, Fos-LI neurones were observed both in the superficial (45 +/- 2%) and deep (37 +/- 1%) laminae of the spinal dorsal horn. 3. Intraplantar morphine dose-dependently reduced c-Fos expression induced 1 h 30 min after carrageenin (r = 0.605, P < 0.02), these effects were completely blocked by intraplantar methiodide naloxone (20 micrograms) (121 +/- 22% of control carrageenin expression). The systemic injection of the highest dose of intraplantar morphine (50 micrograms) had no significant effect on the number of Fos-LI neurones (88 +/- 9% of control carrageenin expression). None of the drugs influenced unilateral peripheral oedema observed 1 h 30 min after carrageenin. 4. In the second series of experiments, intraplantar morphine dose-dependently reduced the number of superficial and deep Fos-LI neurones induced 3 h after carrageenin (r = 0.794, P < 0.0004 and r = 0.698, P < 0.004, respectively). Furthermore, the effects of the highest dose of intraplantar morphine were completely blocked by co-administration of intraplantar methiodide naloxone (20 micrograms). 5. In addition, intraplantar morphine dose-dependently reduced the ankle (r = 0.747, P < 0.002) and paw (r = 0.682, P < 0.005) oedema observed 3 h after carrageenin, with the effect of the highest dose of intraplantar morphine being completely blocked by co-administration of methiodide naloxone (98 +/- 4% and 102 +/- 8% of control paw and ankle oedema, respectively). 6. Brief noxious heat stimulation, in urethane anaesthetized rats, induced, 2 h after the stimulation, numerous Fos-LI neurones in the dorsal horn of L3-L4 lumbar segments of the spinal cord but no detectable peripheral oedema. Fos-LI neurones were preferentially located in superficial laminae (94 +/- 2%) of the spinal dorsal horn. None of the drugs influenced the noxious heat induced c-Fos expression. 7. Such results illustrate that peripheral effects of morphine preferentially occur during inflammatory states and outline the interest of extending clinical investigations of the possible use of local injection of morphine in various inflammatory pain states.

摘要

我们研究了足底注射相同剂量吗啡对足底注射角叉菜胶（6毫克/150微升生理盐水）和有害热刺激（52摄氏度，持续15秒）诱导的脊髓c-Fos表达及炎症反应的影响。2. 在清醒大鼠中，足底注射角叉菜胶可诱导脊髓L4-L5腰段背角中大量Fos样免疫反应性（Fos-LI）神经元以及广泛的外周水肿。在1小时30分钟时，Fos-LI神经元主要位于浅层（74±2%），而在3小时时，在脊髓背角的浅层（45±2%）和深层（37±1%）均观察到Fos-LI神经元。3. 足底注射吗啡剂量依赖性地减少角叉菜胶注射1小时30分钟后诱导的c-Fos表达（r = 0.605，P < 0.02），这些作用被足底注射甲硫氨酸纳洛酮（20微克）完全阻断（为角叉菜胶对照组表达的121±22%）。全身注射最高剂量的足底吗啡（50微克）对Fos-LI神经元数量无显著影响（为角叉菜胶对照组表达的88±9%）。所有药物均未影响角叉菜胶注射1小时30分钟后观察到的单侧外周水肿。4. 在第二组实验中，足底注射吗啡剂量依赖性地减少角叉菜胶注射3小时后诱导的浅层和深层Fos-LI神经元数量（分别为r = 0.794，P < 0.0004和r = 0.698，P < 0.004）。此外，则足底注射甲硫氨酸纳洛酮（20微克）共同给药可完全阻断最高剂量足底吗啡的作用。5. 此外，足底注射吗啡剂量依赖性地减少角叉菜胶注射3小时后观察到的踝关节（r = 0.747，P < 0.002）和爪部（r = 0.682，P < 0.005）水肿，最高剂量足底吗啡的作用被甲硫氨酸纳洛酮共同给药完全阻断（分别为爪部和踝关节水肿对照组的98±4%和102±8%）。6. 在乌拉坦麻醉的大鼠中，短暂的有害热刺激在刺激后2小时诱导脊髓L3-L4腰段背角中大量Fos-LI神经元，但未检测到外周水肿。Fos-LI神经元主要位于脊髓背角的浅层（94±2%）。所有药物均未影响有害热诱导的c-Fos表达。7. 这些结果表明，吗啡的外周作用在炎症状态下优先发生，并概述了扩大对局部注射吗啡在各种炎症性疼痛状态中可能应用的临床研究的意义。