The Australian researchers measured brainstem activity with high-resolution functional MRI (fMRI) in participants as they rated the pain of a hot stimulus applied to their arm.
From this article: “Over two successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labeled ‘lidocaine’ (placebo) and ‘capsaicin’ (nocebo) were acting to modulate their pain relative to a third ‘Vaseline’ (control) cream.”
Placebo and nocebo effects influenced activity in the same brainstem circuit but in opposite ways. The strength of the placebo effect was linked to increased activity in an area called the rostral ventromedial medulla and decreased activity in a nucleus called the periaqueductal gray; the nocebo effect induced the opposite change. These results reveal the role of the brainstem in pain modulation and may offer a route for future treatments of chronic pain.
“Placebo and nocebo effects influenced activity in the same brainstem circuit but in opposite ways. The strength of the placebo effect was linked to increased activity in an area called the rostral ventromedial medulla and decreased activity in a nucleus called the periaqueductal gray; the nocebo effect induced the opposite change. These results reveal the role of the brainstem in pain modulation and may offer a route for future treatments of chronic pain.”
We all ‘handle’ pain in unique ways, and indeed it can be said that pain ‘is all in your head’. Ongoing studies into the impact of the placebo effect is uncovering more of the ways in which we understand and physically process pain. This study reinforces the concept that “pain is not ‘all in your head,’ but in some cases, changing how you think about pain can help you manage it.
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.”
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.
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.