Placeboinduced reductions in pain ratings

1
Placebo-induced reductions in pain ratings
laser evoked potentials A.Watson1, W.
El-Deredy2, D.E. Bentley1, Y.Boyle1, B.A.Vogt3
and A. K. P. Jones1 1Human Pain Research Group,
University of Manchester Rheumatic Diseases
Centre, Hope Hospital, Salford, M6 8HD, UK.
2School of Psychological Sciences, University of
Manchester, Oxford Rd, Manchester M13 9PL 3Dept
of Neuroscience and Physiology, SUNY Upstate
Medical University, 750E. Adams Street, Syracuse,
NY 13210.USA.
138183
Introduction
Summary Conclusions


Mean SEM Pain Rating

• These results show a placebo response on both
  arms when information regarding the application
  site of a placebo analgesic cream was ambiguous.
  This suggests that the placebo effect may not be
  site-specific.
• The reduction in pain rating in the Fully
  Informed session may suggest a residual effect
  from the Conditioning session, the placebo effect
  persisting even though the instructions had
  changed.
• This is the first demonstration of a
  placebo-induced reduction in cortical pain
  processing using LEPs. The effect on the P2 peak
  suggests that placebo affects the cognitive
  evaluation of pain. Further analyses will
  determine whether earlier LEP peaks, reflecting
  sensory processing, are also affected by placebo.
• As LEPs provide a less subjective measure of pain
  than pain ratings, these results suggest that the
  placebo response in this study is not simply due
  to subject compliance.

• Placebo analgesia can be achieved experimentally
  by conditioning, where the pain stimulus is
  reduced to a non-painful level in conjunction
  with the application of a placebo cream in the
  guise of an analgesic drug.
• Benedetti et al. (1999) have shown that
  site-specific instructions regarding the site of
  application of a placebo local anaesthetic
  produces site-specific placebo analgesia.
• We have previously demonstrated that laser pain
  stimuli are a suitable stimulus in placebo
  analgesia studies.

arm A
arm B
Table 1. Stimuli used in each block for both the
Conditioning Fully Informed sessions.
Fig. 1. Comparison of pain ratings from blocks 1
3 for the Conditioning (a) Fully Informed (b)
sessions. indicates a significant difference
from block 1 ( plt0.01, plt0.001).

• In the Fully Informed session subjects were told
  that an inactive cream would be applied to both
  arms. At the start of block 2, subjects were
  told that the pain stimulus may be turned down.
• In the Conditioning session subjects were not
  given any information about the painfulness of
  the stimuli they would receive in block 2.
• LEPs were recorded from 61 electrodes (bandpass
  0.15-70 Hz, A/D rate 500 Hz).
• Pain ratings LEPs were compared between blocks
  using paired t-tests.

• LEP results
• Preliminary analyses focussed on the P2 LEP peak
  (maximal at Cz) for the Conditioning session
  only.
• P2 mean peak latency across the group blocks
  (measured at electrode Cz) was 374 10 ms (SEM)
  for arm A and 380 11 ms for arm B. There were
  no significant differences between blocks 1 3
  for both arms.
• P2 mean peak amplitude at Cz for arm A was
  significantly smaller for block 3 (9.2 2 µv)
  compared with block 1 (20.1 1.5 µv), plt0.05
  (Fig. 2).
• P2 mean peak amplitude at Cz for arm B was also
  significantly smaller for block 3 (9.9 1 µv)
  compared with block 1 (17.6 0.5 µv), plt0.05
  (Fig. 2).

Aims

• To investigate the effect of a placebo-induced
  reduction in pain ratings on the Laser Evoked
  Potential (LEP).
• To test the effect on the placebo response of
  ambiguous information regarding the application
  site of a placebo analgesic cream.

Acknowledgments
Methods
This work was supported by the Arthritis Research
Campaign (UK).
Results
References

• Behavioural Results
• Pain ratings in block 3 were significantly lower
  than those in block 1 for both arms, indicating a
  significant placebo response. This effect was
  seen in both the Conditioning (Fig. 1a) and Fully
  Informed sessions (Fig. 1b), although the effect
  was significantly greater (plt0.001) for the
  Conditioning session for both arms.

• 23 subjects had their forearms randomly labelled
  arm A and arm B.
• Subjects were informed that on one arm they may
  receive a local anaesthetic cream, whereas on the
  other arm they would receive an inactive cream.
  In fact an inactive cream was applied to both
  arms.
• Heat pain from a CO2 laser (pulse duration
  100ms), was adjusted to a level that subjects
  rated as moderately painful (level 7 on a 0 to 10
  pain scale, with level 4 corresponding to just
  painful).
• Subjects underwent 2 sequential sessions a
  Conditioning session and a Fully Informed
  session.
• Sessions differed only in the information
  regarding the nature and effect of the cream.
• Each session consisted of 3 blocks. In blocks I
  3 the stimuli were at the painful level 7 for
  both arms, whereas in block 2 the pain stimuli
  were always turned down to the subjects
  non-painful level 3 at arm A only (Table 1).

Benedetti F. et al.(1999). Somatotopic activation
of opioid systems by target directed expectations
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ery, G.H. Kirsch, I. (1997). Classical
conditioning and the placebo effect. Pain, 72,
103-113. Price, D.D.et al. (1999). An analysis
of factors that contribute to the magnitude of
placebo analgesia in an experimental paradigm.
Pain, 84, 110-113. Voudouris, N.J. et al.
(1990). The role of conditioning and expectancy
in the placebo response. Pain, 43,121-128. Watson
, A. et al. (2005). Placebo induced reduction of
pain intensity unpleasantness ratings of a
laser stimulus. J. Psychophys. 19, (1), 63-64.


Mean SEM Pain Rating
Fig. 2. Significant reduction in P2 peak
amplitude between blocks 3 (red) 1 (black) for
both arms. indicates a significant difference
from block 1 (plt0.05).
arm A
arm B
alison.watson_at_manchester.ac.uk