Effects of propofol anesthesia on the processing of noxious stimuli in the spinal cord and the brain

Drug-induced unconsciousness is an essential component of general anesthesia, commonly attributed to attenuation of higher-order processing of external stimuli and a resulting loss of information integration capabilities of the brain. In this study, we investigated how the hypnotic drug propofol at doses comparable to those in clinical practice influences the processing of somatosensory stimuli in the spinal cord and in primary and higher-order cortices. Using nociceptive reflexes, somatosensory evoked potentials and functional magnet resonance imaging (fMRI), we found that propofol abolishes the processing of innocuous and moderate noxious stimuli at low to medium concentration levels, but that intense noxious stimuli evoked spinal and cerebral responses even during deep propofol anesthesia that caused profound electroencephalogram (EEG) burst suppression. While nociceptive reflexes and somatosensory potentials were affected only in a minor way by further increasing doses of propofol after the loss of consciousness, fMRI showed that increasing propofol concentration abolished processing of intense noxious stimuli in the insula and secondary somatosensory cortex and vastly increased processing in the frontal cortex. As the fMRI functional connectivity showed congruent changes with increasing doses of propofol - namely the temporal brain areas decreasing their connectivity with the bilateral pre-/postcentral gyri and the supplementary motor area, while connectivity of the latter with frontal areas is increased - we conclude that the changes in processing of noxious stimuli during propofol anesthesia might be related to changes in functional connectivity.