We all know about the ‘nocebo’ effect by now – the dark twin of the beneficial placebo effect. For example, a study showed that the pharmacological efficacy of remifentanil (a pain medication) was significantly decreased after patients were told the infusion was stopped during a heat-pain modulation test. Although the infusion had not actually been halted, participants experienced a significant exacerbation of pain even while still receiving remifentanil.
To counter undesirable ‘nocebo’ effects, this article suggests to health practitioners that ‘pragmatic strategies related to patient–practitioner interaction, clinical setting, and context may be implemented to help minimize and prevent the consolidation of negative expectations’.
Pain is something of a mystery. While we all experience it, and experience it in degrees, there’s no ‘gold standard’ for estimating the degree of pain. It seems to be a ‘subjective’ experience. In some of the research literature, such as this study, the placebo effect is given a credible place in the landscape of pain and pain management.
“Placebo effects that arise from patients’ positive expectancies and the underlying endogenous modulatory mechanisms may in part account for the variability in pain experience and severity, adherence to treatment, distinct coping strategies, and chronicity. Expectancy-induced analgesia and placebo effects in general have emerged as useful models to assess individual endogenous pain modulatory systems.”
Meantime, in the category of ‘Out There But Maybe Not As Out There As You Might Think’ virtual reality may have the capacity to harness the placebo effect in pain management.
“Recently, Cedars-Sinai also published research on the clinical utility of a virtual reality intervention in the Inpatient setting. The results of the study were overwhelmingly positive with most patients receiving pain and stress relief from the VR experience.”
More on VR applications here.
We’ve posted elsewhere about the placebo’s dark twin, the nocebo, the phenomenon of the mind provoking negative and damaging effects through the same mechanism that accounts for the positive effects of a placebo.
This paper brings focus to ‘nocebo algesia and hyperalgesia (ie, the occurrence and worsening of nocebo-induced pain, respectively)’ and makes practical suggestions for reducing the incidence of this. As always, these relate to the patient-practitioner relationships and interactions, and strongly reinforce the ‘subjective’ and ‘negotiated’ nature of the experience of pain.
‘In general, the literature shows that uncaring interactions that convey a message of invalidation and lack of warmth may trigger nocebo effects. Avoiding negative communication and interactions with a patient may help to shape a safe and positive environment that not only promotes placebo effects but that also reduces nocebo effects.’
An article in Big Think entitled People are knowingly taking placebos—and its working starts to untangle some of the theories about the functionality of ‘open label’ placebos – which describes the engagement of a placebo effect even when people know they’re taking a placebo.
“Even though they were told that what they were taking was placebo and contained nothing of therapeutic value, those patients who received the placebo reported a 30% reduction in usual pain and maximum pain and a 29% drop in their disability. Incredibly, the placebo worked better than the real pain medication. Participants who took the pain pills reported feeling 9% less usual pain, and 16% less maximum pain. Furthermore, patients taking the real medication reported no change in their level of disability.”
Pain is a subjective state – that’s why practitioners typically ask us to ‘scale’ our experience of it, from a ‘1’ (slight) to a ’10’ (unbearable). And while it’s easy to see why the experience of pain is useful in an evolutionary sense (‘keep your hand out of the fire!’) it’s difficult to account for what mechanism is responsible for this experience. Different analgesics may have different effects (and affects) for different people, and some don’t seem to contraindicate – it seems you can ingest an opioid at the same time as paracetemol.
Enter the placebo effect! Here’s a recent research paper on placebos and pain. And also a fascinating article on ‘leveraging the Placebo Effect to Reduce Opioid Requirements’.
It seems there may be characteristics which not only how receptive you are to benefiting from the placebo effect, but also the degree with which it effects you.
In a study published in Nature Communications, two factors seems to influence results:
- Brain anatomy (such as asymmetry in areas of the brain that control emotion and reward, including the amygdala, accumbens and hippocampus), and
- ‘Personality’ – especially mindsets “emotionally self-aware, attuned to the body and mindful of one’s surroundings”
At Universal Placebos we’ve always known that awareness and mindfulness are part of the therapeutic value of placebos, of course, which is why our product comes bundled with instructions for mindful and meaningful administration.
“Down the line, the clinician could give five or six questions to the patient and decide whether they should just prescribe a sugar pill to them,” say the researchers. “The higher they score on this personality questionnaire, the bigger their placebo response will be.”
Finland’s Arctic circle might not seem like a great place to run a marathon barefoot and in shorts—unless you’re Wim Hof. Hof, better known as “The Iceman,” has attained roughly two dozen world records by completing marvellous feats of physical endurance in conditions that would kill others. Yet even he was understandably nervous the night before his 26-mile jaunt at -4 degrees Fahrenheit.
“What did I get myself into?” he recalls thinking. But from the moment his bare toes hit the snow, he began to feel “surprisingly good.”
MRI scans reveal that Wim Hof artificially induces a stress response in his brain. “By accident or by luck he found a hack into the physiological system,” they say.
How? Well, you know what we think. The placebo effect in action once more!
In Respect the Needle in OA (osteoarthritis), a rheumatologist says:
“… Dealing with osteoarthritis, both patients and their physicians often have a hard time understanding what to make of novel “cures” such as platelet-rich plasma (PRP), stem cell treatments, and so-called prolotherapy.
Although these are typically marketed as halting or reversing joint degeneration in OA, there is virtually no evidence that they actually do. Yet it’s impossible to discount the countless reports from patients that the treatments helped them in terms of pain and function.
The explanation may very well lie in the placebo effect, said Joel Block, MD, a well-known osteoarthritis specialist at Rush University, speaking at the American College of Rheumatology’s 2018 State of the Art Symposium.
But the thrust of Block’s 30-minute talk can be summed up in two words: So what?
The placebo effect is still an effect and a very important one, he argued repeatedly in addressing current knowledge about therapies, largely unregulated, now marketed nationwide in newspapers and online as “disease-modifying.”
It’s “extraordinarily strong” in osteoarthritis, Block said, for reasons that aren’t entirely clear. The experience from randomized trials is that one normally expects a 40% response rate with placebo with large effect sizes. Moreover, the improvements in patient-reported pain do not quickly disappear: the trial data indicates that placebo responses last beyond a year, he said.
“Placebo is active treatment,” Block said.
The placebo effect is one of the most mystifying phenomena in medicine. When we expect a pill to make us feel better, it does. If we see others get better while using a medicine, we will too.
But the placebo effect has an evil twin: the nocebo. It can kick in when negative expectations steer our experience of symptoms and create side effects where none should occur.
This means, incredibly, that you can get side effects from a sugar pill. And sometimes these side effects are so severe that patients drop out of clinical trials. More info here.
Recent evidence suggests that the muscle aches might be a big nocebo.