Remifentanil

Remifentanil, a potent ultra short-acting synthetic opioid painkiller is marketed by drugmakers GlaxoSmithKline and Abbott as Ultiva.

People who don't believe their pain medicine will work can actually reduce or even cancel out the effectiveness of the drug, and images of their brains show how they are doing it, scientists report.

Researchers from Britain and Germany used brain scans to map how a person's feelings and past experiences can influence the effectiveness of medicines, and found that a powerful pain-killing drug with a true biological effect can appear not to be working if a patient has been primed to expect it to fail.

By contrast, positive expectations about the treatment doubled the natural physiological or biochemical effect of an opioid drug among 22 healthy volunteers.

The study of the placebo effect — and its opposite the "nocebo" effect — suggests that neural activity in certain brain areas could be monitored as a way to objectively gauge how well a drug is working for each patient, the researchers said.

"The brain imaging is telling us that patients really are switching on and off parts of their brains through the mechanisms of expectation — positive and negative," said Irene Tracey of Britain's Oxford University, who led the research.

"(The effect of expectations) is powerful enough to give real added benefits of the drug, and unfortunately it is also very capable of overriding the true analgesic effect."

The placebo effect is the real benefit seen when patients are given dummy treatments but believe they will do them good. The nocebo effect is the opposite, when patients get real negative effects when they have doubts about a treatment.

For their study, the scientists used the drug remifentanil, a potent ultra-short-acting synthetic opioid painkiller which is marketed by drugmakers GlaxoSmithKline and Abbott Laboratories as Ultiva. The study was published in the Science Translational Medicine journal.

About the study

Volunteers were put in an MRI scanner and had heat applied to one leg. They were asked to rate pain on a 1 to 100 scale.

Unknown to the volunteers, the researchers started giving the drug via infusion to see what effects there would be when the volunteers had no knowledge or expectation of treatment. The average initial pain rating of 66 went down to 55.

The volunteers were then told they would now start to get the drug, although no change was actually made and they just continued receiving the opioid at the same dose. The average pain ratings dropped further to 39.

The volunteers were then told the drug had been stopped and warned that there may be an increase in pain. In reality, the drug was still being given at the same dose, but their pain intensity increased to 64 — meaning the pain was almost as bad as it had been at the beginning, before they had had any drug.

Looking at scans, the researchers found that the brain's pain networks responded to different extents according to the varying expectations and matched the reports of pain.

Tracey said there may be lessons for the design of clinical trials, which often compare an experimental drug against a dummy pill to see if there is any effect beyond the placebo effect.

"We should control for the effect of people's expectations on the results of any clinical trial," she said. "At the very least we should make sure we minimize any negative expectations to make sure we're not masking true efficacy in a trial drug."

Indeed, in a recent study in the journal IRB: Ethics & Human Research, 60 percent of patients taking part in a clinical trial believed that the experimental drug would control their cancer.

sunday@tribune.com