Effect of Pregabalin on the Median Effective Plasma Concentration of Intravenous Alfentanil in Capsaicin-Induced Pain

• Published in: Pain medicine (Malden, Mass.) Vol. 22; no. 12; pp. 3072 - 3079
• Main Author: Wallace, Mark S
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2021
• Subjects: Alfentanil; Analgesics; Analgesics, Opioid; Capsaicin; Care and treatment; Composition; Dosage and administration; Double-Blind Method; Humans; Hyperalgesia; Intravenous administration; Male; Narcotics; Opioids; Pain; Pain - drug therapy; Pregabalin; Side effects; United States; Opioid; Synergy; Pain; Pregabalin; Experimental; EC; EC50
• ISSN: 1526-2375; 1526-4637; 1526-4637
• DOI: 10.1093/pm/pnab222

Abstract Objective To apply the sequential up–down method to a human experimental pain model in order to examine the opioid-sparing effect of oral pregabalin on intravenous alfentanil. Design Double-blind, randomized, crossover. Setting Academic university medical center. Subjects Thirty-one healthy males. Methods The median effective plasma concentration of intravenous alfentanil was determined under two conditions: alfentanil alone (phase I) and alfentanil+ pregabalin (300 mg orally) (phase II). The alfentanil plasma level (after a computer-controlled infusion) producing a success criterion (at least 30% intradermal capsaicin-induced pain reduction compared with placebo) was used to determine higher or lower doses for each sequential subject. The median dose producing a success criterion and its confidence interval were determined. Results On the basis of the t test for a difference across phase and regression coefficients across groups, there was no opioid-sparing effect of pregabalin on alfentanil. Four subjects in phase I and five subjects in phase II did not complete the study. Two in phase I were technical failures, with the rest in both phases stopped because of side effects. Of the subjects who completed the study, six of 19 subjects in phase I and 11 of 12 subjects in phase II reported side effects. Conclusions When the intradermal capsaicin-induced pain model was used in healthy volunteers, oral pregabalin had no opioid-sparing effects on intravenous alfentanil. This experimental model may be useful in studying analgesic interactions.