HUMAN BRAIN ACTIVITY RESPONSE TO FENTANYL IMAGED BY POSITRON EMISSIONTOMOGRAPHY

Positron emission tomography (PET) is a noninvasive imaging technique that can be used to observe drug actions on human brain in vivo. We us ed O-15-water PET scanning in six volunteers to examine the effects on regional cerebral activity as reflected by regional cerebral blood fl ow (rCBF) of a small intravenous bolus of fentanyl. rCBF was compared between scans obtained after fentanyl or a placebo using three separat e statistical criteria including a pixel-by-pixel t statistic; signifi cance was stringently defined at P values < 0.01. Anatomic locations o f regional cerebral activity changes were verified by aligning rCBF PE T scans with cranial magnetic resonance images using mathematical core gistration. Fentanyl administration was associated with significant in creases in rCBF consistent with regional neuronal activation in both c ingulate and orbitofrontal and medial prefrontal cortices, as well as caudate nuclei. These areas are responsive to nociceptive stimuli and are involved in avoidance learning, reward and addiction, visceromotor control, maintenance of attention, and pain-related affective behavio r. Significant decreases were noted in both frontal and temporal areas and the cerebellum, a distribution far less extensive than that of op iate receptors in general. These data indicate that fentanyl's effects are highly localized and specifically affect cerebral regions associa ted with a range of pain-related behaviors.