PLACEBO-INDUCED CHANGES IN fMRI IN THE ANTICIPATION AND EXPERIENCE OF PAIN
Kirsten Lee
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)
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
5 blocks of 15 trials 1 block -- no cream 2 blocks --“analgesic cream” -placebo 2 blocks --“control cream”
intensemild
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 thalamuscontralateral insularACC
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.