Analgesic and Thermic Effects, and Cerebrospinal Fluid and Plasma Pharmacokinetics, of Intracerebroventricularly Administered Morphine in Normal and Sensitized Rats

Abstract

Abstract The relationship between asthma and opioids has barely been investigated. This study examines whether active sensitization of rats changes the analgesic and thermic effects of intracerebroventricular morphine or the pharmacokinetics of the drug. Morphine (5, 10 and 20 μg) was given intracerebroventricularly to sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague-Dawley rats. The tail-flick latencies and changes in colon temperature were determined before morphine injection and at 30 min intervals for a period of 300 min afterwards. Results were expressed as the area under the time-response curve. The analgesic and hyperthermic response to morphine for sensitized rats was less than that obtained for normal rats. Cerebrospinal fluid and blood samples were collected periodically for a period of 240 min and morphine levels were determined by a highly sensitive radioimmunoassay. The pharmacokinetic parameters half-life, terminal elimination rate constant and the mean residence time were determined in both cerebrospinal fluid and plasma by non-compartmental analysis. The area under the cerebrospinal fluid concentration-time curve from time zero to infinity was higher for sensitized rats than for normal rats for all three doses of morphine but these differences did not correspond with similar changes in pharmacological responses. In conclusion, the attenuated analgesic and thermic responses to intracerebroventricular morphine in the sensitized rats might be a result of pharmacodynamic alterations rather than to pharmacokinetic changes.