Background: Propofol-evoked injection site pain is not observed with fospropofol. We hypothesized that unlike propofol, fospropofol does not activate the irritant receptor, transient receptor potential 1 (TRPA1).
Methods: We tested the hypothesis using electrophysiology and behavioral studies.
Results: Our data demonstrate that propofol (100 μM) evokes an inward current only in TRPA1-expressing neurons. However, fospropofol (100 μM and 1 mM) is unable to evoke depolarizing currents in either TRPA1-positive or TRPA1-negative neurons. Both propofol and fospropofol produced general anesthesia.
Conclusions: The lack of algogenic activity in fospropofol is most likely the result of its inability to activate TRPA1 on nociceptors.