Marcek J M, Seaman W J, Weaver R J
Upjohn Company, Kalamazoo, Michigan 49007.
Pharm Res. 1992 Feb;9(2):182-6. doi: 10.1023/a:1018972920275.
The purpose of this study was to validate an experimental method for quantifying the pain producing potential of intravenously administered solutions. Response was measured in a Broome restraint tube modified by the addition of strain gauges. Struggling caused flexion of the tube, changing strain gauge output and increasing output variance. In experiment 1, five groups of 10 male Sprague Dawley rats were given intravenous injections of 1 ml of saline, acetate, HCl, citric acid vehicles, or KCl over a 1-min period. Results showed significant increases in output variance between saline and treated groups during the infusion period. In experiment 2, five groups of five rats were given intravenous injections of saline or 0.1, 0.05, 0.025, or 0.0125 M KCl. Rats responded in a dose-dependent manner, demonstrating the sensitivity of this technique. In experiment 3, two groups of four rats were given injections of morphine sulfate (2 or 4 mg/kg, ip) prior to administration of 0.05 M KCl. Two additional groups received no pretreatment prior to administration of saline or 0.05 M KCl. Results demonstrate that morphine ablates the response to intravenous administration of KCl. This model provides information concerning the pain producing potential of intravenously delivered compounds or formulations.
本研究的目的是验证一种用于量化静脉注射溶液产生疼痛可能性的实验方法。通过在改良的布鲁姆约束管中添加应变仪来测量反应。挣扎会导致管子弯曲,从而改变应变仪的输出并增加输出方差。在实验1中,将五组每组10只雄性斯普拉格-道利大鼠在1分钟内静脉注射1毫升生理盐水、醋酸盐、盐酸、柠檬酸载体或氯化钾。结果显示,在输注期间,生理盐水组和治疗组之间的输出方差显著增加。在实验2中,将五组每组五只大鼠静脉注射生理盐水或0.1、0.05、0.025或0.0125 M氯化钾。大鼠的反应呈剂量依赖性,证明了该技术的敏感性。在实验3中,两组每组四只大鼠在注射0.05 M氯化钾之前先注射硫酸吗啡(2或4毫克/千克,腹腔注射)。另外两组在注射生理盐水或0.05 M氯化钾之前不进行预处理。结果表明,吗啡可消除对静脉注射氯化钾的反应。该模型提供了有关静脉给药化合物或制剂产生疼痛可能性的信息。