Transcript Placebo-Induced Changes in fMRI in the Anticipation and

PLACEBO-INDUCED CHANGES
IN fMRI IN THE ANTICIPATION
AND EXPERIENCE OF PAIN
Wager, T.D., Rilling, J.K., Smith, E.E., Sokolik, A.,
Casey, K.L., Davidson, R.J., Kosslyn, S.M., Rose, R.M.,
Cohen, J.D. (2004)
Kirsten Lee
Introduction

Placebo analgesic effect: the belief that one
is receiving analgesic treatment reduces pain

Response bias OR influence on sensory,
affective, cognitive pain processing?

fMRI -investigate neural mechanism and time
course of placebo effect
Hypothesis

Placebo
 decreases reported pain – behavioural
 decreases activity of pain ROIs during
pain stimulation – brain
 creates expectation for pain relief (PFC
activation) which inhibits pain
processing
Experimental Task: Study 1

Subjects were scanned by fMRI (BOLD) as
they received electric shocks to the right wrist
treated with “ineffective/analgesic”
(ctrl/placebo) cream
Procedure: Study 1

Intense vs mild shock: identified pain ROIs
intense
mild

5 blocks of 15 trials
1
block -- no cream
 2 blocks --“analgesic cream” -placebo
 2 blocks --“control cream”
Experimental Task: Study 2

Subjects were scanned by fMRI as thermal
stimuli were applied to patches of skin on the
left forearm treated with “ineffective/analgesic”
(ctrl/placebo) cream
Procedure: Study 2

Calibrate temperatures to reported pain
levels of 2, 5, 8 (max 10)

Manipulation phase:
 Participants
were told all stimuli at level 8
 Applied level 8 heat to ctrl patch, level 2 heat
to placebo patch
Procedure: Study 2

Test phase:
 Applied

level 5 heat to both patches
Identical stimuli-- differences in reported pain
(ctrl-placebo) attributed to placebo effects
Results

Identified pain-responsive regions:
 Rostral
anterior cingulate cortex (rACC)
 Anterior cingulate cortex (ACC)
 Secondary somatosensory cortex (SII)
 Thalamus (TH)
 Insula (INS)

Reported pain: control > placebo (22%)
Results

Magnitude of placebo reduction in
reported pain correlates with
magnitude of placebo reduction in pain
ROI activity of
 contralateral
thalamus
 contralateral insula
 rACC

during pain stimulation
Results

Placebo-induced increase in dorsolateral
PFC, orbitofrontal cortex, rACC activity
during anticipation correlates with
 Behavioural
and brain placebo effects
 Increased periaqueductal grey (PAG in
midbrain) activity during anticipation
Results

In insula and thalamus, main placebo
effects were found in the late heat period,
after stimulus offset
Time (s)
Results: Summary
Placebo induced:
1. ↓ reported pain (behavioural placebo effect)
2. ↓ TH, INS, rACC activity during pain
stimulation (brain placebo effect)
3. ↑ dlPFC, OFC, rACC, PAG activity during
anticipation
4.
INS and TH show placebo effects in late
heat period
Discussion

Correlation between behavioural and brain
placebo effects (TH, INS, rACC) during pain
stimulation

Placebo
 inhibits afferent sensory pain transmission (TH)
 has an effect on sensory-discriminative or
affective components of pain (INS)

Strongly refutes response bias
Discussion

Placebo increases prefrontal (dlPFC/OFC)
and midbrain (PAG) activity during
anticipation

PFC regions responsible for generating
expectation for pain relief contribute to placebo
analgesia

Expectancy process may be related to opioid
system activation in PAG
Discussion

Predominant brain placebo effects occur late
in thermal pain response

Placebo effects may:
 require a period of pain to develop
 involve opioid mechanisms triggered by
prolonged pain
 involve cognitive reappraisal of pain (positive
reinterpretation)

A major portion of the placebo effect is likely
controlled centrally by specific pain regions
Strengths and Limitations

Comprehensive, well-organized report and
discussion of results

Restricted analysis of PFC activation during
anticipation to dlPFC and OFC

Repeated stimulation of same area - alter
pain sensation?
Further Research

Activity of other PFC regions during
anticipation

Investigate role of rACC in pain processing
THANK YOU!
Wager, T.D., Rilling, J.K., Smith, E.E., Sokolik, A., Casey, K.L., Davidson, R.J.,
Kosslyn, S.M., Rose, R.M., Cohen, J.D. 2004. Placebo-induced changes in fMRI
in the anticipation and experience of pain. Science 303(5661):1162-7.