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.