Positive Expectations Boost Pain-Relieving Effects of Opioids
When your doctor prescribes a new pain medication for you, do you expect it to relieve your pain? Or are you skeptical, thinking it’s probably not going to help much? According to a study published in the journal Science Translational Medicine, your expectations may significantly influence the effectiveness of the treatment.
Study Design and Results
Researchers studied the effectiveness of the opioid remifentanil by assessing the responses of 22 healthy volunteers to a painful stimulus under three different conditions. Remifentanil is an intravenous (IV) opioid analgesic used to prevent or treat post-surgical acute pain.
Heat was applied to a leg of each participant at a level that would result in a pain rating of approximately 70 points on a 1-to-100 scale. In addition to the subjects self-reporting increases and/or decreases in pain, functional magnetic resonance imaging (fMRI) was used to record brain activity.
Before beginning the three experiments, each participant had an IV drip established so that researchers could control how much, if any remifentanil was being administered without the knowledge of the subject. Prior to receiving any of the opioid, the average initial pain rating was 66.
Part 1: Without knowing that the researchers had actually begun administering the remifentanil, participants’ pain ratings decreased by an average of 11 points to 55. This established the baseline analgesic effect of the remifentanil itself, without any expectations.
Part 2: Subjects were told that the medication was starting to be administered, however, no change was actually made in the remifentanil dose already being given. At this point, the pain ratings dropped to an average of 39 points. This additional pain reduction could be considered a placebo effect.
Part 3: Participants were told that the medication had been stopped and warned that the pain might increase, although in fact there was still no change in the remifentanil dose being administered. Following the warning, pain ratings jumped back up to an average of 64 points. This increase in pain perception might be considered a nocebo (opposite of a placebo) effect.
Interestingly, the fMRI scans revealed that the brain responses of the subjects corresponded with their expectations. When they expected a reduction in pain, there was increased activity in the areas of the brain associated with rational cognitive functions and reward anticipation. On the other hand, when participants expected increased pain, there was increased activity in areas of the brain known to control mood and anxiety.
The researchers concluded, "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." They go on to suggest that integrating patients’ beliefs and expectations into drug treatment plans may improve treatment outcomes.
I find this study fascinating. It demonstrates just how powerful our minds and attitudes really are. The opioid by itself only resulted in a 17 percent decrease in pain, but when positive expectations were added in, pain levels dropped an additional 29 percent What is equally amazing is that when negative expectations were thrown into the mix, pain levels returned to within two points of what they were prior to receiving the medication. This shows that we can actually negate the therapeutic effects of opioid medications if we don’t expect them to work.
The personal lesson I take away from this study is that I need to do whatever I can to maintain positive expectations for my treatment plan. But I think there is also a responsibility for physicians to present new treatments in a manner that will foster positive expectations in their patients.
Bingel U, et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med. 2011 Feb 16;3(70):70ra14.