Fuctional Magnetic Resonance Imaging Exploit Study On Butorphanol Tartrate NS Effects On Human Brain

Purposes: To study how the central nervous system(CNS) analgesics effect the functional state of human brain by nasal spray with functional magnetic resonance imaging (fMRI), to observe brain activation resulting from drug administration, to discuss the possible opioid receptors distri- bution in the CNS of human brain, and to access the application values and reliability of pharmacological fMRI under the way of nasal spray.Materials and methods: Eighteen healthy right handed subjects without nasal cavity diseases, nine males and nine females, aged 21-23 years (mean 22.5 years) participated in the behavioral pretest and the formal fMRI study. Each subject gave a written consent for participation before the experiment. In the behavioral pretest all the volunteers kept quiet at least half an hour and wrote down all the subjective sensations during one hour after nasal spray. The actual fMRI experiment were performed two weeks later and butorphanol tartrate nasal spray were administrated to the unilateral nostril of subjects and one-day intervals saline was performed by the same way.Experiment reagent: Butorphanol tartrate Nasal Spray was made by Hengrui Medicine company in Shanghai and its National Medicine Permit No.H20046359. At the entrance of the medicine phial there was a ration atomization device to ensure 1mg per nasal spray .Experiment design: Block Design combined with sensory stimulation was adopted in this study. The painful stimulation to the dorsum of hand tasks were divided into two groups: left hand and right hand was given painful stimulation respectively. Each group task corresponded to 6 on blocks and 7 off blocks:"on-"represented to begin painful stimulation tothe dorsum of hand , accordingly"off-"represented to stop painful stimulation, each of which all lasted 30 seconds. Each group task totally went on 429 seconds and finished 143 scans to obtain 143 functional images with the first 5 images and the last 8 images wiped off. One EPI scanning which made the right and left dorsum painful stimulation tasks done added up to 260 scans (260 fMRI images) .Experiment scanning: The MRI examinations were performed using GE Signa 1.5T echospeed MR/I scanner and a standard head coil. Firstly sagittal T1WI images was acquired using SE sequence. And its scan parameter: TR 390 ms,TE 11 ms, slice thickness 7mm,intervals 1.5mm, number of slices 12,matrix 256×160,fields of view 24cm,NEX 1. During the experiment period, the fMRI measurements were performed using a gradient-echo echo-planar sequence, its pitching line as usual, and its scan parameter: TR3000ms ,TE40ms, slice thickness 3mm,intervals 1mm,number of slices 30,fields of view 256mm,matrix 64×64,NEX 143.Two times of EPI scanning were proceeded during the experimental tasks, and the first EPI scanning began after 17 minutes after nasal spray and the other began at 25 minutes. Each EPI scanning lasted 429 seconds and finished 143 scans. All subjects were demanded to write down all the feelings after the experiments.Post-disposing of experiment datum: The raw fMRI datum were disposed by software Matlab6.5/Matlab5.3 and SPM2, et al .The experiment adopted t>3.11,p<0.01.Results:1. The acting time of Butorphanol NS mainly lies in 15-35 mintues after nasal spray through the behavioral pretest so as to determine the MRI scanning period.2.Butorphanol NS induced multiple cortical and subcortical brain activation. The main cortical activation areas lies in : obitofrontal gyrus, medial superior frontal gyrus, superior frontal gyrus, the opercular section of frontal lobe and parietal lobe, anterior and middle cingulated cortex, insula cortex, hippocampus, parahippocampal gyrus, precuneus, middle temporal gyrus, inferior temporal gyrus, occipital lobe. The main subco- rtical activation areas lies in: pallidum. The main cerebellum activationareas lies in : cerebellum 6-9, vemis, cerebellum crura.3.Different period has different brain activation areas,nearer to the half-peak time, bigger the intensity and quantity of its activation.Conclusion:1.Behavioral pretest helps to determine the scanning time and medicine acting time.2.The opioid receptors mainly distribute at prefrontal lobe(obitofrontal gyrus, medial superior frontal gyrus, superior frontal gyrus), paralimbic cortices (cingulated cortex and hippocampus), insular cortex,pallidum and the opercular section of frontal lobe and parietal lobe. These results corresponded with the classic theories on PET neurorecepotors imaging.3.The differences of brain activations at different periods after nasal spray in some extent explain the phfMRI techniques have the possibility of becoming the tools to discuss the mechanism of medicine under the way of nasal spray and intranasal brain-targeting fMRI studies will become one alternative way to access the drug action by nasal spray.