A novel approach for the determination of the pain-producing potential of intravenously injected substances in the conscious rat

Abstract

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.