Narcotic Analgesic Mechanism Of Functional Magnetic Resonance Imaging Study

Part 1 Brain Activity Changes Associated with Fentanyl Analgesia as Revealed by fMRIObjectiveTo investigate the cortical representation of von Frey filaments stimulaion and the brain regions related to analgesic effect of fentanyl by functional magnetic resonance imaging at 3.0 T.MethodsTwenty healthy male volunteers were randomly divided into 2 groups:group F1 (fentanyl=1μg&g,n=10) and group F2(fentanyl=1.5μg/kg,n=10).Mechanical stimuli were applied to the center of the left foot by von Frey filaments with mechanical pain thresholds and VAS scores been evaluated.FMRI examinations were performed 1 week after that pilot study with the following sequences:structure imaging and functional imaging:functional imaging=stimulus sequence P1 +fentanyl sequence+stimulus sequence P2;4min20s stimulus sequence =(20s on+20s off)×6 times,this sequence was repeated after fentanyl sequence;12min fentanyl sequence = baseline scan 4min + bolus fentanyl 1μg/kg or 1.5p.g/kg + balance scan 8min.The monitoring data were collected during the scanning.FMRI data were processed by SPM2 and Matlab 6.5 software packages.Results1.Areas activated by 300g vFFs were(P＜0.001,uncorrected):bilateral anterior cingulate gyrus(ACC),contralateral(right) insula,primary somatic sensory cortex (SI),temporal lobe,frontal lobe,and parietal lobe;2.In respond to 300g vFFs with 1μg/kg fentanyl: Activation areas of(P2—P1) were:ipsilateral(left) cingulate gyrus,precuneus and bilateral temporal lobe;Activation areas of(P1—P2) were null;3.In respond to 300 g vFFs with 1.5μg/kg fentanyl:Activation areas of(P2—P1) were:bilateral cingulate gyrus,contralateral(right) insula and SI;Activation areas of(P1—P2) were null;4.Active brain regions of(F2—F1) after the bolus of fentanyl under vFFs stimulation were observed in ipsilateral cingulate gyrus and precuneus;Active brain regions of(F1—F2) after the bolus of fentanyl under vFFs stimulation were null.Conclusion1.The activation of brain regions as cingulate gyrus,insula,SI may attribute to the mechanical pain;2.It is assumed that the activation of cingulate gyrus attribute to the analgesic effect of fentanyl dose-dependently;3.Cingulate gyrus is the brain region which could be activated by either mechanical stimuli or fentanyl,however,not cover the same sub-region,it indicates that cingulate gyrus is likely the target of analgesic effect of fentanyl. Part 2 Effects of Propofol on Brain Activation in Respond to Mechanical Stimuli Imaged by fMRIObjectiveTo investigate the brain regions related to the effects of propofol on mechanical stimuli by functional magnetic resonance imaging at 3.0 T.MethodsTwenty healthy male volunteers were randomly divided into 2 groups:light anesthesia group(group L)(BIS 60～80) and deep anesthesia group(group D)(BIS 40～60).Propofol was administrated by target controlled infusion system in pilot study. The target effect site concentration(ESC) of propofol was defined as the average of the ESC from BIS 80 to 60 or BIS 60 to 40 in group L or group D respectively,von Frey filaments were used as mechanical stimuli applied to the center of the left foot, pain threshold and VAS scores were evaluated.FMRI examinations were taken 1 week after pilot study with the following sequences:structure imaging+ functional imaging:functional imaging =stimulus sequence+ propofol sequence;stimulus sequence=6×(20s on+20s off),this sequence was repeated after propofol sequence;15min propofol sequence=4min baseline scan+ 9min TCI propofol scan+2 min balance scan.The monitoring data were collected during the scanning.FMRI data were processed by SPM2 and Matlab 6.5 software package.Results1.ESC of propofol in group L is 1.52±0.28μg/ml;while ESC in group D is 2.50±0.55μg/ml. 2.In group L,active brain regions of(P2—P1) were observed in:cingulate gyrus, thalamus and cerebellum;while active brain regions of(P1—P2) were observed in:temporal lobe,frontal gyrus,and occipital lobe;3.In group D,active brain region of(P2—P1) was observed only in cerebellum;while active brain regions of(P1—P2) were observed in:cingulate gyrus, thalamus,brainstem,temporal lobe,frontal gyrus,and occipital lobe;4.Active brain regions of(deep—low) with propofol infusion in response to vFFs stimulation were observed in cerebellum and frontal lobe;Active brain region of(low—deep) with propofol infusion in response to vFFs stimulation was null.Conclusion1.TCI propofol,either in low ESC or in deep ESC,affect the activation of brain regions induced by mechanical stimuli in a different way,cingulate gyrus,thalamus and cerebellum may be the targets of analgesic action of propofol.2.It is assumed that in different brain regions propofol effect may differ in various degree of concentration.