REGIONAL BRAIN ACTIVITY CHANGES ASSOCIATED WITH FENTANYL ANALGESIA ELUCIDATED BY POSITRON EMISSION TOMOGRAPHY

Recent positron emission tomography (PET) studies have demonstrated ar eas of pain processing in the human brain. Given the inhibitory effect s of opioids on neuronal activity, we predicted that fentanyl's analge sic effects would be associated with suppression of pain-evoked respon ses in these distinct brain areas. To test this, PET was used to measu re cerebral blood flow responses, as reflections of regional neuronal activity, to painful and nonpainful thermal stimuli both in the absenc e and presence of fentanyl in humans. During each PET scan in nine hea lthy volunteers a tonic heat source was placed against the subject's l eft forearm, delivering a preset temperature of either 40 degrees C (n onpainful) or 47-48 degrees C (painful). Subjects underwent eight bloo d flow studies, each consisting of 50 mCi [O-15] water injection and a PET scan. The first four studies were performed during placebo admini stration in the stimulus sequence: nonpainful, painful, painful, nonpa inful. This sequence was then repeated during intravenous (IV) adminis tration of fentanyl 1.5 mg/kg. Significant differences in regional cer ebral blood flow (rCBF) between the placebo and the fentanyl condition s during nonpainful and painful stimuli were identified using statisti cal parametric mapping. It was found that pain increased rCBF in the a nterior cingulate, ipsilateral thalamus, prefrontal cortex, and contra lateral supplementary motor area. Fentanyl increased rCBF in the anter ior cingulate and contralateral motor cortices, and decreased rCBF in the thalamus (bilaterally) and posterior cingulate during both stimuli . During combined pain stimulation and fentanyl administration, fentan yl significantly augmented pain-related rCBF increases in the suppleme ntary motor area and prefrontal cortex. This activation pattern was as sociated with decreased pain perception, as measured on a visual analo g scale. In contrast to our hypothesis, these data indicate that fenta nyl analgesia involves augmentation of pain-evoked cerebral responses in certain areas, as well as both activation and inhibition in other b rain regions unresponsiveness to pain stimulation alone.