The reproducibility of placebo

analgesia.

Debbie Morton

Human Pain Research Group

Pre-cream phase Conditioning phase Post-cream phase

placebo group (not told)

control group (told)

1) Placebo Group

“You will receive either an inactive cream or a local anaesthetic cream but you will not be told which.”

2) Control Group

“You will receive an inactive cream that will have no analgesic effect.”

69 Healthy Volunteers: Two Sessions: Three Experimental Phases

Cream

Watson et al. 2006 Pain

Repeatability

Treatment Group

-2.00

0.00

2.00

4.00

6.00

-2.00 -1.00 0.00 1.00 2.00 3.00 4.00 5.00 6.00

Session 1

Ses

sio

n 2

Control Group

-1.00

-0.50

0.00

0.50

1.00

1.50

2.00

-0.60 -0.10 0.40 0.90 1.40

Session 1

Ses

sio

n 2

r = 0.01

r = 0.79

-2 0 2 4 6

Mean change in pain on conditioned arm (pre-post

conditioning)

Control distribution

Sham treatment

distribution

97.5% Threshold

individual change in pain

- sham treatment group

(arbitrary value on y

axis)

individual change in pain

- control group

(arbitrary value on y

axis)

Modelling the placebo response

Distributions of the individual mean responses generated using a simple hierarchical model with individual mean responses for the placebo group. The threshold line marks the 97.5th percentile of the control distribution

Placebo response session 2

No response session 2

Placebo response session 1

13 4

No response session 1

1 20

State anxiety -0.34084 0.15492 -2.2001 0.035

LOT-R optimism 0.37185 0.15120 2.4593 0.019

β SE T-stat P-value

Regression model to predict placebo response

Predictors were for the second session only

Expectation of pain relief in

session 2

Dispositional optimism

Placebo response in session 1

Decrease in state anxiety in session

2

Placebo response in session 2

Control Placebo

1 1

2 2

** P<0.05

** P<0.05

Am

plitu

de µ

VA

mpl

itude

µV

Am

plitu

de µ

VA

mpl

itude

µV

Time (ms)

Time (ms)

Time (ms)

Time (ms)

Pre-cream

Post-cream LEP at Cz

The stimulus preceding negativity SPN

• Observed during pain anticipation

• Late phase has been localised to the an area commonly associated with nociception

-3500ms 3000 2500 2000 1500 1000 500 0 PAIN

Am

plitu

de µ

V

Recording the Stimulus Preceding Negativity (SPN)

Control Placebo

SPN at CPzA

mpl

itude

µV

Am

plitu

de µ

VA

mpl

itude

µV

Am

plitu

de µ

V

Time (ms)

Time (ms)Time (ms)

Time (ms)

1

2 2

1

Pre-cream

Post-cream

**p<0.05

Conclusions

• The placebo response is reproducible

• Optimism predicts a repeatable response

• A placebo response reduces state anxiety

• The placebo group have a lower post conditioning anticipatory response