The placebo effect is well known. Tell someone, “Hey, this pill will make your headache go away” and, though the pill is just a sugar pill and has no pain mediating qualities, will indeed make the headache go away in some small percentage of the population. The placebo effect is the power of suggestion in medicine.

The placebo effect has a kind of evil twin, known as the nocebo effect. If I tell you that the placebo pill you are taking will have the side-effects of dry mouth and diarrhea, guess what you’ll be more likely to experience? So here is the problem. With real medicines with real side-effects, those side-effects are more likely to occur if the patient knows about them. So we have ourselves a dilemma here. I as a hypothetical doctor have two options: 1) warn you about all possible side-effects because it is my duty to ensure you are informed so you can care for yourself or 2) not warn you about all possible side-effects because my doing so is a potentially harmful act, worsening your condition. What is a doctor good to do? What would you want your doctor to do?

Penny Sarchet, winner of the Wellcome Trust Science Writing prize, dives into how scientists are working to counter the dreaded nocebo so that being informed doesn’t mean being in pain.

Until recently, we knew very little about how the nocebo effect works. Now, however, a number of scientists are beginning to make headway. A study in February led by Oxford’s Professor Irene Tracey showed that when volunteers feel nocebo pain, corresponding brain activity is detectable in an MRI scanner. This shows that, at the neurological level at least, these volunteers really are responding to actual, non-imaginary, pain. Fabrizio Benedetti, of the University of Turin, and his colleagues have managed to determine one of the neurochemicals responsible for converting the expectation of pain into this genuine pain perception. The chemical is called cholecystokinin and carries messages between nerve cells. When drugs are used to block cholecystokinin from functioning, patients feel no nocebo pain, despite being just as anxious.

The findings of Benedetti and Tracey not only offer the first glimpses into the neurology underlying the nocebo effect, but also have very real medical implications. Benedetti’s work on blocking cholecystokinin could pave the way for techniques that remove nocebo outcomes from medical procedures, as well as hinting at more general treatments for both pain and anxiety. The findings of Tracey’s team carry startling implications for the way we practise modern medicine. By monitoring pain levels in volunteers who had been given a strong opioid painkiller, they found that telling a volunteer the drug had now worn off was enough for a person’s pain to return to the levels it was at before they were given the drug. This indicates that a patient’s negative expectations have the power to undermine the effectiveness of a treatment, and suggests that doctors would do well to treat the beliefs of their patients, not just their physical symptoms.


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