n-(3-fluoropropyl)-n-nordiprenorphine and Pain

The endogenous opioid system is involved in many body functions including pain processing and analgesia. To determine the role of basal opioid receptor availability in the brain in pain perception, twenty-three healthy subjects underwent positron emission tomography (PET) utilizing the subtype-nonselective opioid antagonist [(18)F]diprenorphine, quantitative sensory testing (QST) and the cold pressor test. Binding potentials (BPs) were calculated using a non-invasive reference tissue model and statistical parametric mapping was applied for t-statistical analysis on a voxelwise basis. We found that cold pain-sensitive subjects present a significantly lower BP in regions including the bilateral insular cortex and the left orbitofrontal cortex. In addition, correlation analysis revealed an inverse correlation between opioid BP in the bilateral motor and premotor region and perceptual wind-up. These findings indicate that interindividual differences in pain perception are partially accounted for by basal opioid receptor availability. A secondary aim of this study was to investigate the contribution of basal opioid receptor availability to the perception of non-nociceptive stimuli. The following negative correlations between regional opioid BP and scores of QST parameters were found: BP in the right premotor cortex and scores of alternating cold and warm stimuli, BP in the left midcingular cortex and scores of cold detection threshold, BP in the left insula and scores of mechanical detection threshold. These results suggest that the opioid receptor system is involved in the perception not only of pain but also of non-painful somatosensory stimuli.

Topics: Adult; Brain; Brain Chemistry; Cold Temperature; Data Interpretation, Statistical; Diprenorphine; Humans; Male; Middle Aged; Pain; Pain Threshold; Perception; Physical Stimulation; Positron-Emission Tomography; Pressure; Radiopharmaceuticals; Receptors, Opioid; Sensation; Sensory Thresholds; Somatosensory Cortex; Young Adult

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri- and subgenual part of "classical ACC" only), midcingulate cortex (MCC, posterior part of "classical ACC"), putamen, caudate nucleus and the amygdala. BP for [(18)F]fluoroethyl-diprenorphine was lowest in the sensory motor strip (0.30). Highest BP was found in thalamus (1.36), basal ganglia (putamen 1.22, caudate 1.16) and amygdala (1.21). In the cingulate cortex, ACC (1.11) had higher BP than MCC (0.86). In the operculo-insular region, we found high BPs in all ROIs: anterior insula (1.16), posterior insula (1.05), frontal operculum (0.99) and parietal operculum (0.77). Factor analysis of interindividual variability of opiate receptor BP revealed four factors (95% explained variance): (1) operculo-insular areas, ACC, MCC and putamen, (2) amygdala and thalamus, (3) caudate and thalamus, (4) SI/MI and MCC. Nociceptive areas of the lateral pain system (frontoparietal operculum and insula) have opiate receptor BPs significantly higher than SI/MI, comparable to anterior and midcingulate areas of the medial pain system. These findings suggest that the cortical anti-nociceptive effects of opiates are not only mediated by ACC and MCC, but also by the operculo-insular cortex, if it can be assumed that opioid binding mediates anti-nociception in those structures.

Topics: Adult; Brain; Diprenorphine; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nociceptors; Pain; Positron-Emission Tomography; Receptors, Opioid