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Placebo analgesia Predrag Petrovic, MD, PhD Karolinska Institute, Stockholm, Sweden Wellcome Institute of congnitive Neuroscience, London, UK.

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Presentation on theme: "Placebo analgesia Predrag Petrovic, MD, PhD Karolinska Institute, Stockholm, Sweden Wellcome Institute of congnitive Neuroscience, London, UK."— Presentation transcript:

1 Placebo analgesia Predrag Petrovic, MD, PhD Karolinska Institute, Stockholm, Sweden Wellcome Institute of congnitive Neuroscience, London, UK

2 Cognition and pain

3 Ret SBlSTTaSTT Amy PAG PBn dlPT / LC RVM mObfc vmPfc rACC cACC lObfc Ant Ins Post Ins MDvcILVMp/bVMPVPLVPI S2 / iPC S1 Hyp vlPFC Basal ganglia

4 Main effect of pain Petrovic et al Science 295 ( ) 2003

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10 Jackson et al Neuroimage Can we feel pain wihout noxious input

11 Jackson et al Neuroimage Can we feel pain wihout noxious input

12 Anticipation of pain Jensen et al Neuron

13 Empathy for pain Singer et al Science

14 vs. Saarel et al Cerebral Cortex 2006 Empathy for pain

15 Petrovic et al Pain 85 (1-2) 2000 Distraction and pain

16 ?

17 Cognitive modulation of pain

18 Placebo analgesia

19 Bottlenecks in Placebo analgesia ExpectationOpioid system

20 Pain presentation Treatment expectation and Placebo analgesia Expectation manipulation and learning Placebo manipulation Rating: 75 Rating: 25Rating: 50 Voundouris et al J Per Soc Psychol 48 (47-53) 1985 Voundouris et al pain 38 ( ) 1989 Voundouris et al pain 43 ( ) 1990 Montgomery and Kirsch Pain 72 ( ) 1997 Placebo cream

21 Opioid analgesiaPlacebo analgesia Naloxone -- The Opioid system and Placebo analgesia

22 pop wop pplwpl w p Heat Pain Non-painful Warrm stim Opioids (remifentanil) Placebo (saline) No treatment Placebo and opioid analgesia Petrovic et al Science 295 ( ) 2003

23 Pain network Petrovic et al Science 295 ( ) 2003

24 Opioid effects and Placebo analgesia (PPL – P)(POP+WOP)-(P+W) Petrovic et al Science 295 ( ) 2003

25 Orbitofrontal cortex (PPL – P) Petrovic et al Science 295 ( ) 2003

26 Kong et al. J Neurosci Jan 11;26(2): Placebo and expectation modulation

27 Bingel et al. Pain Jan;120(1-2):8-15 Placebo and expectation modulation

28 Wager et al. Science Feb 20;303(5661): Placebo and expectation modulation

29 Wager et al. Science Feb 20;303(5661): Placebo and expectation modulation

30 Lieberman et al. Neuroimage May;22(1): Placebo in chronic pain patients

31 Placebo analgesia effect - activation of cognitive modulatory network

32 ACC and Placebo

33 Opioid effects and Placebo analgesia Petrovic et al Science 295 ( ) 2003

34 The Cortical Opioid System Rostral ACC Willoch et al 1999

35 High Placebo respondersLow Placebo responders Opioid analgesia (POP-P) Petrovic et al Science 295 ( ) 2003

36 Opioid receptor imaging Zubieta et al 2005

37 Filelds et al Nature NeuroscienceReviews 2004

38 POPPPLP Regression analysis Petrovic et al Science 295 ( ) 2003

39 Emotional Counting Stroop Counting Stroop Three Murder Bush et a. Trends in Cognitive Sciences 4 (6) 2000 ACC and Cognition - Conflict monitoring or conflict resolution ?

40 Anterior Cingulate Cortex: –Interaction with cognitive attentional systems that regulate conflicting processes. – Modulation of pain processing through opioid system.

41 Obfc / vlPFC and Placebo

42 Placebo. Petrovic et al 2002 Petrovic et al Science 295 ( ) 2003

43 Opioid effects: Placebo effects:

44 Opioid effects: Placebo effects:

45 Relation between rACC and vlPFC in Placebo 1

46 Orbitofrontal cortex - goals and expectations

47 Orbitofrontal cortex - goals and expectations

48 Orbitofrontal cortex - goals and expectations

49 Aversive temporal difference prediction error Seymour et al Nature Neuroscience 8 ( ) 2005

50 Anterior Cingulate Cortex: –Interaction with cognitive attentional systems that regulate conflicting processes. – Modulation of pain processing through opioid system. Orbitofrontal Cortex: –Emotional and motivational goals and expectations. –Computing errors between expected and real outcome.

51 Emotional Placebo

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53 International Affective Picture System (IAPS)

54 Pain presentation Manipulation of treatment expectation Expectation manipulation and learning Placebo manipulation Rating: 75 Rating: 25Rating: 50 Voundouris et al J Per Soc Psychol 48 (47-53) 1985 Voundouris et al pain 38 ( ) 1989 Voundouris et al pain 43 ( ) 1990 Montgomery and Kirsch Pain 72 ( ) 1997 Placebo cream

55 Lanexate i.v. Bezodiazepines i.v IAPS Day 1 – Induction of expectation Rating of unpleasantness

56 Day 2 - fMRI of the placebo effect IAPS x3 Rating of unpleasantness 36 Information: Bezodiazepines (Anxiety reducing drug) 51 Information: Lanexate (No anxiety reduction)

57 Placebo och unpleasantness - activation of cognitive modulatory network Petrovic et al Neuron - In Press

58 Placebo och unpleasantness - correlation with the expectation effect Petrovic et al Neuron - In Press

59 Relation between rACC and vlPFC in Placebo PET-study fMRI-study

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61 Prof Martin Ingvar Prof Per Hansson Prof Eija Kalso Katrina Carlsson Karl Magnus Petersson Per Hamid Ghatan Peter Fransson Jesper Andersson


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