placebo analgesia predrag petrovic, md, phd karolinska institute, stockholm, sweden wellcome...
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Placebo analgesia
Predrag Petrovic, MD, PhDKarolinska Institute, Stockholm, Sweden
Wellcome Institute of congnitive Neuroscience, London, UK
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Cognition and pain
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Ret
SBlSTTaSTT
Amy
PAG
PBn
dlPT / LC
RVM
mObfc
vmPfc
rACC
cACC
lObfc
Ant Ins
Post Ins
MDvcILVMp/bVMP VPL VPI
S2 / iPC
S1Hyp
vlPFC
Basal gangliaBasal ganglia
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Main effect of pain
Petrovic et al Science 295 (1737-1740) 2003
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Jackson et al Neuroimage 771-779 2005
Can we feel pain wihout noxious input
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Jackson et al Neuroimage 771-779 2005
Can we feel pain wihout noxious input
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Anticipation of pain
Jensen et al Neuron 40 1251-1257 2003
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Empathy for pain
Singer et al Science 1157-1152 2004
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vs.
Saarelet al Cerebral Cortex 2006
Empathy for pain
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Petrovic et al Pain 85 (1-2) 2000
Distraction and pain
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?
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Cognitive modulation of pain
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Placebo analgesia
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Bottlenecks in Placebo analgesia
Expectation Opioid system
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Pain presentation
Treatment expectation and Placebo analgesia
Expectation manipulationand learning
Placebo manipulation
Rating: 75 Rating: 25 Rating: 50
Voundouris et al J Per Soc Psychol 48 (47-53) 1985Voundouris et al pain 38 (109-116) 1989Voundouris et al pain 43 (121-128) 1990Montgomery and Kirsch Pain 72 (107-113) 1997
Placebo cream Placebo cream
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Opioid analgesia Placebo analgesia
Naloxone
- -
The Opioid system and Placebo analgesia
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pop wop
ppl wpl
wp
HeatPain
Non-painfulWarrm stim
Opioids (remifentanil)
Placebo (saline)
No treatment
Placebo and opioid analgesia
Petrovic et al Science 295 (1737-1740) 2003
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Pain network
Petrovic et al Science 295 (1737-1740) 2003
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Opioid effects and Placebo analgesia
(PPL – P)(POP+WOP)-(P+W)
Petrovic et al Science 295 (1737-1740) 2003
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Orbitofrontal cortex
(PPL – P)
Petrovic et al Science 295 (1737-1740) 2003
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Kong et al. J Neurosci. 2006 Jan 11;26(2):381-8.
Placebo and expectation modulation
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Bingel et al. Pain. 2006 Jan;120(1-2):8-15
Placebo and expectation modulation
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Wager et al. Science. 2004 Feb 20;303(5661):1162-7.
Placebo and expectation modulation
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Wager et al. Science. 2004 Feb 20;303(5661):1162-7.
Placebo and expectation modulation
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Lieberman et al. Neuroimage. 2004 May;22(1):447-55.
Placebo in chronic pain patients
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Placebo analgesia effect- activation of cognitive modulatory network
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ACC and Placebo
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Opioid effects and Placebo analgesia
Petrovic et al Science 295 (1737-1740) 2003
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The Cortical Opioid System
Rostral ACC
Willoch et al 1999
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High Placebo responders Low Placebo responders
Opioid analgesia
(POP-P)(POP-P)
Petrovic et al Science 295 (1737-1740) 2003
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Opioid receptor imaging
Zubieta et al 2005
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Filelds et al Nature NeuroscienceReviews 2004
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POP PPL P
Regression analysis
Petrovic et al Science 295 (1737-1740) 2003
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Emotional Counting Stroop
Counting Stroop
ThreeThreeThreeThree
MurderMurderMurderMurder
Bush et a. Trends in Cognitive Sciences 4 (6) 2000
ACC and Cognition - Conflict monitoring or conflict resolution ?
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• Anterior Cingulate Cortex: – Interaction with cognitive attentional systems
that regulate conflicting processes.– Modulation of pain processing through opioid
system.
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Obfc / vlPFC and Placebo
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Placebo. Petrovic et al 2002
Petrovic et al Science 295 (1737-1740) 2003
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Opioid effects:
Placebo effects:
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Opioid effects:
Placebo effects:
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Relation between rACC and vlPFC in Placebo 1
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Orbitofrontal cortex- goals and expectations
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Orbitofrontal cortex- goals and expectations
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Orbitofrontal cortex- goals and expectations
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Aversive temporal difference prediction error
Seymour et al Nature Neuroscience 8 (1234-1240) 2005
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• 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.
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Emotional Placebo
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Emotional Placebo
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International Affective Picture System (IAPS)
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Pain presentation
Manipulation of treatment expectation
Expectation manipulationand learning
Placebo manipulation
Rating: 75 Rating: 25 Rating: 50
Voundouris et al J Per Soc Psychol 48 (47-53) 1985Voundouris et al pain 38 (109-116) 1989Voundouris et al pain 43 (121-128) 1990Montgomery and Kirsch Pain 72 (107-113) 1997
Placebo cream Placebo cream
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Lanexate i.v.
Bezodiazepines i.v.
5129
61
IAPS IAPS IAPS
Day 1 – Induction of expectation
Rating of unpleasantness
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Day 2 - fMRI of the placebo effect
IAPS IAPSx3
Rating of unpleasantness
36
Information:Bezodiazepines(Anxiety reducing drug)
51
Information:Lanexate(No anxiety reduction)
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Placebo och unpleasantness- activation of cognitive modulatory network
Petrovic et al Neuron - In Press
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Placebo och unpleasantness- correlation with the expectation effect
Petrovic et al Neuron - In Press
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Relation between rACC and vlPFC in Placebo
PET-study fMRI-study
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Prof Martin IngvarProf Per HanssonProf Eija Kalso
Katrina CarlssonKarl Magnus Petersson
Per Hamid GhatanPeter Fransson
Jesper Andersson