Placebo and Opioid Analgesia Imaging a Shared Neuronal

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 VOL 295 1737~1740 強伍翎

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

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

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

＊Experiment ◎ Purpose To compare analgesic effect between placebo and opioid treatment. ◎ Material Placebo— Saline Opioid— Remifentanil (0. 5μg/Kg) Nine people

◎ 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, 70 s Nonpainful wram stimulation— 38°C, 70 s

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

＊Result ◎ Behavior Result (1) P (2) P (3) PPL POP Placebo responder — Low (<10%) — High (>10%)

◎ PET Result I. (1)Main effect of Pain [(POP+PPL+P)-(WOP+WPL+W)] + P=0. 005 +w)

◎ PET Result (continued) (2) Main effect of Opioid [(POP+WOP)-(P+W)] P=0. 001 P=0. 005

◎ PET Result (continued) (3) Effect of Placebo (during pain) (PPL-P) P=0. 001 P=0. 005

◎ PET Result (continued) Placebo mask with opioid network P=0. 005

◎ PET Result (continued) II. Compare high and low placebo responder in PPL-P and POP-P P= 0. 005 Z=4. 77 High placebo responder Low placebo responder Z=3. 24

◎ PET Result (continued) III. Regression analysis Covariation between r. ACC and the brainstem Blue — r. ACC P=0. 005 n. s. = subsignificant changes

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

＊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.

＊Doubt and reflection ◎ II