Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain’s role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained.

Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However it is not clear whether the placebo response is reproducible within individuals and what role personality traits might play in predicting it. We induced placebo analgesia by conditioning subjects to expect pain reduction following a sham-treatment in the guise of a local anaesthetic cream applied to one arm. Pain ratings were assessed before, during and after treatment. The procedure was repeated in a second session to assess the degree of reproducibility of the response. A high degree of correlation was found between the two sessions for the sham-treatment group (R(2) = 0.55; p < 0.001). Personality questionnaires were given during both experimental sessions to assess key traits such as optimism and state and trait anxiety. A regression model was used to statistically define a placebo responder in terms of personality scores. High dispositional optimism and low state anxiety were found to be significant predictors of placebo response. We suggest that repeated placebo responders are high in dispositional optimism and having a placebo response in the first session causes a drop in state anxiety at the beginning of the repeat session.

Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However, the response to placebo treatment is highly variable. It is unclear how anticipatory and pain-evoked potentials are affected by the treatment and how reproducible the response is. Laser stimulation was used to induce moderate pain in healthy volunteers. We induced placebo analgesia by conditioning subjects to expect pain reduction by applying a sham anaesthetic cream on one arm in conjunction with a reduced laser stimulus. Pain ratings were assessed before, during and after treatment. Using lectroencephalography (EEG) we measured anticipatory neural responses and pain-evoked potentials to laser heat to determine how expectation of analgesia affected the response to a placebo manipulation. This was a reproducibility study and as such the experimental procedure was repeated after a minimum gap of 2 weeks. Significant reductions in pain-evoked potentials were shown after treatment. The anticipatory responses did not change after treatment for the control and sham-treatment groups in the first session but were significantly lower in the repeat session relative to the first session in the sham-treatment group only. A significant correlation was found between the reduction in state anxiety in the repeat session relative to the first and the reduction in the anticipatory response in the sham-treatment group. Receiving a placebo treatment appears to cause a lasting change in the cognitive processing of pain for at least 6 weeks. This cognitive change may be facilitated by a change in state anxiety.