1. Placebo and Opioid Analgesia - Imaging a Shared Neuronal Network Predrag Petrovic, Karl Magnus Petersson, Eija Kalso,Martin Ingvar Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Stockholm 171 76, Sweden., Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Finland. SCIENCE VOL295 1737~1740 強伍翎

2. ＊ Background ◎ Brain (1) Oribitofrontal cortex (2) Brainstem(PAG, pon) (3) Thalamus (4) CC (ACC, rACC, caudal ACC)

3. ＊ Background (continued) ◎ Pain ◎ Endogenous opioid system (receptor and ligand), analgesia and antagonist ◎ Importance of ACC (rACC) in opioid effect

4. ＊ Background (continued) ◎ Placebo analgesia and effect ◎ PET (Positron emission tomography ) ◎ rCBF (regional cerebral blood flow)

5. ＊ Experiment ◎ Purpose To compare analgesic effect between placebo and opioid treatment. ◎ Material Placebo— Saline Opioid— Remifentanil (0.5μg/Kg) Nine people

6. ◎ Method Standard pain-stimulus paradigm (1) POP (heat pain with opioid treatment) (2) WOP (warm nonpain 〃 ) (3) PPL(heat pain with placebo treatment) (4) WPL (warm nonpain 〃 ) (5) P (heat pain only) (6) W (warm nonpain 〃 ) Heat pain— 48°C, 70s Nonpainful wram stimulation— 38°C, 70s

7. ◎ Method (continued) Double Blind(for OP and PL) Inform subject for no analgesia Each person 2 blocks Study (1) Behavior Response — VAS (2) rCBF — PET(450MBq[ 15 O]H 2 O)

8. ＊ Result ◎ Behavior Result (1) P POP (2) P PPL (3) PPL POP Placebo responder — Low ( 10%)

9. ◎ PET Result I. (1) Main effect of Pain [(POP+PPL+P)-(WOP+WPL+W)] w) + + P=0.005

10. ◎ PET Result (continued) (2) Main effect of Opioid [(POP+WOP)-(P+W)] P=0.001 P=0.005

11. ◎ PET Result (continued) (3) Effect of Placebo (during pain) (PPL-P) P=0.005P=0.001

12. ◎ PET Result (continued) Placebo mask with opioid network P=0.005

13. ◎ PET Result (continued) II. Compare high and low placebo responder in PPL-P and POP-P High placebo responder Low placebo responder POP-P P= 0.005 Z=4.77Z=3.24

14. ◎ PET Result (continued) III. Regression analysis Covariation between rACC and the brainstem Blue — rACC P=0.005 n.s.= subsignificant changes

15. ＊ Conclusion ◎ Both opioid and placebo are associated with increased activity in rACC ◎ A covariation between activity in rACC and brainstem during both opioid and placebo analgesia, but not pain-only A related neural mechanism in placebo and opioid analgesia.

16. ＊ Suggestion ◎ Orbitofrontal cortex has dense connection with ACC and brainstem, therefore suggest these region belong to a network using cognitive cue to activate the endogenous opioid system.

17. ＊ Doubt and reflection ◎ II