Differential right shifts in the dose-response curve for intrathecal morphine and sufentanil as a function of stimulus intensity

Abstract

To assess effects of stimulus intensity, dose-response curves in rats for radiant heat-evoked withdrawal of the hind paw was assessed after the intrathecal (i.t.) injection of sufentanil and morphine, mu-opioid agonists differing in intrinsic activity, at Low, Medium, and High stimulus intensities. Baseline latencies observed at the 3 intensities were: low = 14.5 ± 0.3; medium = 8.9 ± 0.2; high = 5.7 ± 0.1 sec. After i.t. administration of sufentanil or morphine, there was a dose-dependent, naloxone-reversible elevation in nociceptive threshold. With increased stimulus intensity, there was a right shift in the dose-response curves with morphine exhibiting a greater magnitude right shift than that of sufentanil. Dose ratios (ED 50 Medium/ED 50 Low and ED 50 High/ED 50 Low) with 95% CI for sufentanil were, respectively, 2.5 (2.2–2.9) and 7.7 (6.7–8.9), and the dose ratio for morphine (ED 50 Medium/ED 50 Low) was 34 (28–41). At the highest intensity, due to a plateau in the morphine dose-response curve, ED 50 and dose ratio calculations could not be performed. The present study supports the pharmacological model of receptor occupany, such that the higher efficacy receptor agonist, sufentanil, demonstrated a lesser magnitude right shift than the lower efficacy agonist, morphine, while at the high stimulus intensity, morphine but not sufentanil, was a partial agonist.