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 Pain

Repeatability r = 0.01 r = 0.79

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 No response session 1 120

State anxiety LOT-R optimism 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 ** P<0.05 Amplitude µV 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

Amplitude µV Recording the Stimulus Preceding Negativity (SPN)

Control Placebo SPN at CPz Amplitude µV Time (ms) 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