Synergistic analgesic effect of propofol-alfentanil combination through detecting the inhibition of cAMP signal pathway.

Objective The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol–alfentanil combination. Methods The synergistic analgesic effects of propofol–alfentanil combination in Sprague–Dawley (SD) rats were analysed through the von Frey test. Then, we examined the activity of phospholipase C (PLC) and the intracellular levels of Ca2+ and adenosine 3′, 5′cyclic monophosphate (cAMP) in primary neuronal cells of fetal SD rats. We detected the intracellular Ca2+ concentration by fluorescence and flow cytometry. The PLC activity of the primary neuronal cells was assayed using the EnzChek® Direct Phospholipase C Assay Kit. The cAMP content of the cells was assayed using the cAMP Direct Immunoassay Kit (Fluorometric). Key findings Both propofol and alfentanil treatments depressed cAMP levels and PLC activity, but propofol–alfentanil combination decreased these parameters to a greater extent than alfentanil treatment alone. Propofol and alfentanil both inhibited Ca2+ channel, but propofol–alfentanil combination suppressed this channel to a greater extent than alfentanil treatment alone. Fluorescent image analysis revealed that both propofol and alfentanil reduced the intracellular levels of Ca2+, and propofol–alfentanil combination showed weaker signals than alfentanil alone. Propofol–alfentanil combination significantly reduced intracellular Ca2+ level, cAMP level and PLC activity. Conclusion Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.