Negativity tied to Pain

Abstract
The gold standard for determining the efficacy of biomedical therapies is the detection of a significant difference between the therapeutic effects of an active pharmacological agent or procedure and a matched inert placebo in a randomized controlled trial.
Detecting this difference has become a challenge for medicine, especially for outcomes that are based on patient self-rated scales.
Yet factors that contribute to placebo responses have received scant attention.
In this issue of Science Translational Medicine, Bingel et al. report on an example of how noninvasive whole-brain imaging contributes to our understanding of brain-based placebo effects.
Here we highlight ways in which neuroimaging is catalyzing a revolution in society's perspective of placebo effects by providing a compelling visualization of how brain activities that reflect a person's thoughts, feelings, and past experiences can enhance or antagonize his or her response to a medical treatment.

Abstract
Evidence from behavioral and self-reported data suggests that the patients' beliefs and expectations can shape both therapeutic and adverse effects of any given drug.
We investigated how divergent expectancies alter the analgesic efficacy of a potent opioid in healthy volunteers by using brain imaging.
The effect of a fixed concentration of the μ-opioid agonist remifentanil on constant heat pain was assessed under three experimental conditions using a within-subject design:
1) with no expectation of analgesia,
2)with expectancy of a positive analgesic effect, and
3) with negative expectancy of analgesia (that is, expectation of hyperalgesia or exacerbation of pain).
We used functional magnetic resonance imaging to record brain activity to corroborate the effects of expectations on the analgesic efficacy of the opioid and to elucidate the underlying neural mechanisms.
Positive treatment expectancy substantially enhanced (doubled) the analgesic benefit of remifentanil.
In contrast, negative treatment expectancy abolished remifentanil analgesia.
These subjective effects were substantiated by significant changes in the neural activity in brain regions involved with the coding of pain intensity.
The positive expectancy effects were associated with activity in the endogenous pain modulatory system, and the negative expectancy effects with activity in the hippocampus.
On the basis of subjective and objective evidence, we contend that an individual's expectation of a drug's effect critically influences its therapeutic efficacy and that regulatory brain mechanisms differ as a function of expectancy.
We propose that it may be necessary to integrate patients' beliefs and expectations into drug treatment regimes alongside traditional considerations in order to optimize treatment outcomes.