The problem of opioid analgesic addiction is not a major problem in current medical treatment, but there is no alternative effective analgesic means. Placebo analgesia reveals how social, cognitive, and emotional processing directly affect pain. Recently, Lauren Y. Atlas from the National Institute of Alternative Medicine and Integrative Health interpreted research on placebo analgesia and highlighted how people's expectations, emotions, and social contexts affect the placebo effect and its neural mechanisms.
The review was published in Trends in Cognitive Sciences under the title "A social affective neuroscience lens on placebo analgesia."
Summary of key points
Placebo analgesia research provides a fresh perspective on how pain and clinical outcomes are affected by social, cognitive, and emotional processing.
The clinical setting and doctor-patient relationship modulate the effectiveness of pain medications by changing people's expectations, emotions, and providing social support.
Placebo analgesia has similar psychological mechanisms to other types of placebo effects, both shared and different neurological mechanisms.
Placebo studies have important implications for reducing health disparities and addressing the opioid crisis.
Pain researchers should work with psycho-emotional neuroscientists to explore the relationship between pain, emotion, and social situations to promote human health.
Placebo analgesia: opens a window into the effects of social, cognitive, and emotional processing on pain
The placebo effect refers to the positive therapeutic effect caused by the psychological and social factors of the treatment, and unrelated to the pharmacological and biological properties of the treatment itself. The nocebo effect is the opposite of the placebo effect: increased pain or side effects caused by psychological or social factors of treatment. The placebo effect depends on previous experience (e.g., reflex learning) and clear beliefs (e.g., oral instructions). The striatum and orbitofrontal cortex are associated with clear beliefs, while the amygdala is associated with pure empirical learning.
The framework for computational modeling provides a new perspective on the interpretation of the placebo effect. The degree to which pain perception is biased toward prior expectation depends on the precision of the expectation—the more precise the expectation, the stronger the impact on pain perception. Emotions also affect pain sensations, negative emotions enhance pain sensations and positive emotions can relieve pain. Previous studies have found that placebos also reduce negative emotions, such as anxiety and fear; conversely, placebos increase feelings of anxiety.
Doctors' attitudes, behaviors, and doctor-patient relationships also affect the effectiveness of clinical treatment and pain perceptions. For example, the stronger the patient feels the doctor's empathy for himself, the better the treatment will be.
The neural mechanism of placebo analgesia and the specificity of pain
Previous studies have found that placebo analgesia causes neurophysiological mechanisms similar to drug analgesia.
Both placebo analgesia and opioid analgesia cause pre-beaking cingulate gyrus (rACC) brain region activity. In addition, the placebo activates the dorsolateral prefrontal lobe (DLPFC), rACC, and peri-catheter gray matter (PAG) with a high μ μ-opioid receptor density (MOR). Most importantly, the antagonist of ingestion of MOR blocks the placebo effect, which means that the placebo is analgesic through endogenous MOR. In addition to being involved in pain regulation, MOR also has an impact on emotional and social interactions. Meta-analysis found that placebo analgesia reduced brain regions associated with pain-affecting components such as the anterior cingulate gyrus, insular lobes, and thalamus (significant networks, salience networks).
Thus, the placebo effect may not simply reduce pain perception, but also affect the emotional and social component associated with pain. In fact, meta-analysis found that although analgesics and placebos had similar oral reporting effects on analgesia, the drug's effect on specific pain signatures (NPS) was about 10 times greater than that of placebo.
The effect of placebo on pain-related brain regions was greatly influenced by the intensity of the placebo effect in the participants, while placebo-activated DLPFC and rACC were highly heterogeneous. This is a step closer to showing that the effect of placebo on pain is moderated by other factors.
The placebo analgesic effect is not limited to the effect on pain perception, but can also be generalized to emotional and social interactions. While participants were told that treatment could relieve pain and reduce anxiety, although participants only underwent conditional learning about pain, placebo significantly reduced pain and anxiety in participants. In addition, placebos have also been found to reduce the negative impact of social rejection. Right-sided DLPFC is thought to be the neural basis for generalization of the placebo effect.
Conclusion
Exploring how expectations, emotions, and social situations of treatment outcomes affect pain and clinical outcomes will help us achieve better clinical outcomes and increase patient happiness by directly intervening in these mental processes. Only when pain researchers join forces with clinicians and social-emotional neuroscientists will it be possible to make real progress in addressing the opioid epidemic, reducing pain health disparities, and improving health.
bibliography
Atlas LY. A social affective neuroscience lens on placebo analgesia. Trends Cogn Sci. 2021 Nov;25(11):992-1005. doi: 10.1016/j.tics.2021.07.016. Epub 2021 Sep 16. PMID: 34538720; PMCID: PMC8516707.
Compiled by Maru (brainnews creative team)
Reviewer: Simon (Brainnews Editorial Board)