A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate

To elucidate the mechanism of propofol-induced pain on injection, we perfor med several studies using nafamostat mesilate, a kallikrein inhibitor, or l idocaine. As both pretreatment and low-dose mixing with nafamostat produced the same effects on pain reduction, we used the latter method in the follo wing experiments. Low-dose mixing had the same effect on injection pain as mixing with lidocaine. The extent of pain was assessed by measuring bradyki nin concentrations by mixing with blood. Propofol and its lipid solvent mix ed with blood produced approximately two-fold generation of bradykinin comp ared with the saline control, and this was inhibited completely by nafamost at and lidocaine. Injection of the lipid solvent before propofol significan tly aggravated pain compared with prior injection of saline, although the l ipid solvent injected twice caused no change in pain. These results suggest that the lipid solvent for propofol activates the plasma kallikrein-kinin system and produces bradykinin which modifies the injected local vein. This modification of the peripheral vein may increase the contact between the a queous phase propofol and the free nerve endings of the vessel, resulting i n aggravation of propofol-induced pain.