Traub R J, Stitt S, Gebhart G F
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA.
Brain Res. 1995 Dec 1;701(1-2):175-82. doi: 10.1016/0006-8993(95)00990-5.
We have previously reported that repetitive, noxious colorectal distention (CRD) induces c-Fos in the lumbosacral spinal cord. This study examined the effects of the analgesics morphine and tramadol on c-Fos expression resulting from noxious CRD in the rat. Pre-treatment (30 min or 1 min, i.v.) with morphine (1.25 mg/kg-5.0 mg/kg) or tramadol (1 mg/kg-20 mg/kg) dose-dependently attenuated c-Fos expression to CRD in all areas of the L6-S1 spinal gray matter. The highest dose of morphine was equipotent to the highest dose of tramadol. Repetitive dosing (1/4 of the greatest dose every 30 min) was as effective as a single bolus dose for both drugs. The visceromotor response to CRD was dose-dependently attenuated by tramadol and was reversed by naloxone. However, the dose of tramadol that eliminated the visceromotor response (7% of control) reduced the c-Fos expression to 47% of control. These results demonstrate that these two analgesics attenuate immediate-early gene expression and the visceromotor response to a noxious visceral stimulus and suggest that complete attenuation of c-Fos expression is not necessary for these compounds to produce analgesia to a noxious visceral stimulus.
我们之前曾报道，重复性有害结肠扩张（CRD）可诱导腰骶脊髓中的c-Fos表达。本研究检测了镇痛药吗啡和曲马多对大鼠有害CRD所致c-Fos表达的影响。用吗啡（1.25mg/kg - 5.0mg/kg）或曲马多（1mg/kg - 20mg/kg）进行预处理（静脉注射，30分钟或1分钟），可剂量依赖性地减弱L6 - S1脊髓灰质所有区域对CRD的c-Fos表达。吗啡的最高剂量与曲马多的最高剂量等效。重复给药（每30分钟给予最大剂量的1/4）对两种药物而言与单次推注剂量效果相同。曲马多剂量依赖性地减弱对CRD的内脏运动反应，且该反应可被纳洛酮逆转。然而，消除内脏运动反应的曲马多剂量（为对照的7%）将c-Fos表达降低至对照的47%。这些结果表明，这两种镇痛药可减弱即时早期基因表达以及对有害内脏刺激的内脏运动反应，并提示这些化合物产生对有害内脏刺激的镇痛作用并不需要完全减弱c-Fos表达。
