Acute analgesic effects of DBS and change in [11C]DPN binding. (A) Change in pain scores with DBS stimulation assessed during home trial. The analgesic effect of stimulation was almost completely lost 60 min after inactivation of DBS (pain VAS increased from 2.5±0.8 to 4.4±1.3, p<0.05, n=5) to reach a plateau level of pain that continued for more than two hours. On re-commencing PAG stimulation the analgesic effect was evident within 30 min (pain VAS reduced by 41% from 5.1±1.8 to 3.0±1.2) and this analgesic action was maintained for the rest of the test period. (rm-ANOVA with Dunnett's posthoc tests, *,# – p<0.05; **, ## – p<0.01, ***,### – p<0.001.). (B) Timeline of the sequential [15O]water and [11C]DPN scans with the first scanning session following 60 min after DBS was stopped and the second commencing 60 min after DBS was reinstated. Shown alongside is a representative sagittal parametric image of the volume of distribution (VT) for [11C]DPN overlaid on T1-weighted MRI image for a single subject (h00635) with DBS off. The image shows a characteristic distribution of the opioid ligand with high binding in the thalamus, midbrain and in several cortical regions (such as prefrontal and cingulate) but low binding in the occipital cortex and the pontine nucleus.