Analgesic and Antihyperalgesic Properties of Propofol in a Human Pain Model

Background: Propofol (Disoprivan (R), AstraZeneca AG, Zug, Switzerland) has long been considered to be nonanalgesic. However, accumulating evidence shows that propofol possesses modulatory action on pain processing and perception. In this study, the authors investigated the modulatory effects of propofol and a formulation similar to the solvent of propofol (10% Intralipid (R); Fresenius Kabi, Stans, Switzerland) on pain perception and central sensitization in healthy volunteers. Methods: Fourteen healthy volunteers were included in this randomized, double-blind, placebo-controlled, crossover study. Intracutaneous electrical stimulation (48.8 +/- 25.8 mA) induced spontaneous acute pain (Numeric Rating Scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia were assessed regularly before, during, and after a 45-min target-controlled infusion (2 mu g/ml) of propofol, the solvent 10% Intralipid (R), and saline. Results: During administration, propofol significantly decreased pain scores and areas of hyperalgesia and allodynia compared with both 10% Intralipid (R) and saline (placebo-corrected mean Numerical Rating Scale score reduction by propofol: 38 +/- 28%). This difference disappeared shortly after cessation of the infusion. Thereafter, no significant group differences were observed in the Numerical Rating Scale score and the areas of hyperalgesia or allodynia. However, there was a trend to reduced hyperalgesia and allodynia after propofol treatment. Pharmacodynamic modeling regarding the analgesic effect of propofol showed an EC50 (half-maximum effect site concentration) of 3.19 +/- 0.37 mu g/ml. Ten percent Intralipid (R) was free of pain-modulatory effects in the authors' experiments. Conclusions: Propofol showed short-lasting analgesic properties during its administration, whereas the solvent-like formulation 10% Intralipid (R) had no effect on pain perception.