Effects of general anesthetics on substance P release and c-Fos expression in the spinal dorsal horn

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We examined the effects of general anesthetics on formalin-induced substance P release and c-Fos expression in superficial dorsal horn. Fentanyl, but not propofol, pentobarbital, isoflurane nor nitrous oxide alone inhibited NK1 receptor internalization (NK1Ri). However, isoflurane+nitrous oxide reduced NK1Ri. All agents reduced c-Fos expression in the superficial dorsal horn.General anesthetics at anesthetic concentrations block spinal neuronal activation through a mechanism which is independent of an effect upon small primary afferent peptide release. The effect of fentanyl alone and the synergistic effect of isoflurane and nitrous oxide on substance P release suggests a correlative rationale for the therapeutic use of these anesthetic protocol by blocking nociceptive afferent transmitter release and preventing the initiation of cascade which are immediately postsynaptic to the primary afferent.