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Placebo analgesia
Predrag Petrovic, MD, PhDKarolinska Institute, Stockholm, Sweden
Wellcome Institute of congnitive Neuroscience, London, UK
Cognition and pain
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
Main effect of pain
Petrovic et al Science 295 (1737-1740) 2003
Jackson et al Neuroimage 771-779 2005
Can we feel pain wihout noxious input
Jackson et al Neuroimage 771-779 2005
Can we feel pain wihout noxious input
Anticipation of pain
Jensen et al Neuron 40 1251-1257 2003
Empathy for pain
Singer et al Science 1157-1152 2004
vs.
Saarelet al Cerebral Cortex 2006
Empathy for pain
Petrovic et al Pain 85 (1-2) 2000
Distraction and pain
?
Cognitive modulation of pain
Placebo analgesia
Bottlenecks in Placebo analgesia
Expectation Opioid system
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
Opioid analgesia Placebo analgesia
Naloxone
- -
The Opioid system and Placebo analgesia
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
Pain network
Petrovic et al Science 295 (1737-1740) 2003
Opioid effects and Placebo analgesia
(PPL – P)(POP+WOP)-(P+W)
Petrovic et al Science 295 (1737-1740) 2003
Orbitofrontal cortex
(PPL – P)
Petrovic et al Science 295 (1737-1740) 2003
Kong et al. J Neurosci. 2006 Jan 11;26(2):381-8.
Placebo and expectation modulation
Bingel et al. Pain. 2006 Jan;120(1-2):8-15
Placebo and expectation modulation
Wager et al. Science. 2004 Feb 20;303(5661):1162-7.
Placebo and expectation modulation
Wager et al. Science. 2004 Feb 20;303(5661):1162-7.
Placebo and expectation modulation
Lieberman et al. Neuroimage. 2004 May;22(1):447-55.
Placebo in chronic pain patients
Placebo analgesia effect- activation of cognitive modulatory network
ACC and Placebo
Opioid effects and Placebo analgesia
Petrovic et al Science 295 (1737-1740) 2003
The Cortical Opioid System
Rostral ACC
Willoch et al 1999
High Placebo responders Low Placebo responders
Opioid analgesia
(POP-P)(POP-P)
Petrovic et al Science 295 (1737-1740) 2003
Opioid receptor imaging
Zubieta et al 2005
Filelds et al Nature NeuroscienceReviews 2004
POP PPL P
Regression analysis
Petrovic et al Science 295 (1737-1740) 2003
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 ?
• Anterior Cingulate Cortex: – Interaction with cognitive attentional systems
that regulate conflicting processes.– Modulation of pain processing through opioid
system.
Obfc / vlPFC and Placebo
Placebo. Petrovic et al 2002
Petrovic et al Science 295 (1737-1740) 2003
Opioid effects:
Placebo effects:
Opioid effects:
Placebo effects:
Relation between rACC and vlPFC in Placebo 1
Orbitofrontal cortex- goals and expectations
Orbitofrontal cortex- goals and expectations
Orbitofrontal cortex- goals and expectations
Aversive temporal difference prediction error
Seymour et al Nature Neuroscience 8 (1234-1240) 2005
• 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.
Emotional Placebo
Emotional Placebo
International Affective Picture System (IAPS)
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
Lanexate i.v.
Bezodiazepines i.v.
5129
61
IAPS IAPS IAPS
Day 1 – Induction of expectation
Rating of unpleasantness
Day 2 - fMRI of the placebo effect
IAPS IAPSx3
Rating of unpleasantness
36
Information:Bezodiazepines(Anxiety reducing drug)
51
Information:Lanexate(No anxiety reduction)
Placebo och unpleasantness- activation of cognitive modulatory network
Petrovic et al Neuron - In Press
Placebo och unpleasantness- correlation with the expectation effect
Petrovic et al Neuron - In Press
Relation between rACC and vlPFC in Placebo
PET-study fMRI-study
Prof Martin IngvarProf Per HanssonProf Eija Kalso
Katrina CarlssonKarl Magnus Petersson
Per Hamid GhatanPeter Fransson
Jesper Andersson