Follow along with the video below to see how to install our site as a web app on your home screen.
Note: This feature may not be available in some browsers.
Quick note - the problem with Youtube videos not embedding on the forum appears to have been fixed, thanks to ZiprHead. If you do still see problems let me know.
You should watch it before you make any bets!
The study looked at neural activity in the brains of mice. Neural circuit basis of placebo pain relief (Nature, July 24, 2024)
You should watch it before you make any bets!
The study looked at neural activity in the brains of mice. Neural circuit basis of placebo pain relief (Nature, July 24, 2024)
Then you should be able to tell me what makes it sound to you as if it is about "controlling the subjective (!) perception of pain":
Placebo effects are striking demonstrations of mind-body interactions 1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain, a phenomenon known as placebo analgesia 3–6. However, despite the strength of placebo effects and their impact on everyday human experience and failure of clinical trials for new therapeutics 7, the neural circuit basis of placebo effects has remained elusive. Here, we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn), a pre-cerebellar nucleus with no established function in pain. We created a behavioral assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.
I don't disagree with you when you say that it is about (hypothetically, potentially) "controlling the sense of pain," but that's not what arthwollipot said, and that is not what the study itself was about. They just think that their "findings (!) open the possibility (!) of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain," but not even that sounds subjective to me.
ETA: You will get a better idea of the whole thing if you watch the video (11 min.) or maybe just read the transcript:
0:00 Placebo Effect in a nutshell
1:05 Placebo and nocebo
1:40 History of placebo
2:30 So many studies
3:20 Neural pathways and previous discoveries
4:30 Animals also feel placebo
5:30 New study using mice
6:55 Brain pathway discoveries
8:10 Optogenetics to confirm this
9:20 Why this matters
My initial look at the paper has not thrown up a lot of red flags, though I find it interesting that a lot of people who seem to be doing research on placebo effects appear to be Chinese.
One co-author is from Harvard, but I can't see any obvious links to the thoroughly discredited acupuncturist Ted Kapchuk, so no red flags there either.
Science communication is often about relating complex ideas in a clear and concise way. Unfortunately, the discourse around the placebo effect is anything but. The term ‘placebo effect’ is often used in casual conversation, popular media, and even academia as if it represents a single, well-understood phenomenon. In reality, ‘the’ placebo effect is a convoluted mess of unrelated effects that confound clinical trials.
For example, the National Institutes of Health in the US says the placebo effect works by ‘turning on the body’s natural mechanisms for helping us feel better.’ This statement is a gross oversimplification. Some placebo responses may be due to triggering the release of dopamine or endorphins, but not every placebo response can be chalked up to these mechanisms.
...
So when headlines appear claiming ‘We may finally know how the placebo effect relieves pain’ (New Scientist, 24 July 2024), we have good reason to be skeptical. There is no singular placebo effect, and no singular mechanism by which it modifies pain. Conditioning, bias, and mood can all influence reported pain to varying extents, and all are part of the placebo response. At best this discovery, whatever it is, may explain some parts of some placebo effects, but can we really say, ‘we finally know’?
Poor work, arthwollipot.
You quote from the introduction to the article instead of from what the article is actually about, i.e."What happened in the study".
That's a weird place to stop. Did you even read the rest of the article, which is about the mouse study that I first referred to in my post about this video about it:
What Mike Hall seems to dislike about the new study is that it seems to actually avoid the pitfalls of many earlier studies, i.e. the "convoluted mess of unrelated effects that confound clinical trials."
The interesting question is: Is there such a thing as actual pain relief in the body's (including the brain's) response to pain due to expectations? And the new study appears to confirm that, yes, there is. And it doesn't stop there. It also pinpoints what appears to be the neurological response that causes the pain relief.
The study manages to eliminate two of the biggest confounding factors:
1) from the participants who don't want to disappoint the doctors/researchers who appear to be keen on relieving the pain of their patients/test subjects.
2) from the doctors/researchers who would like to see their treatment/test show a positive result.
And "regression to the mean" and "parallel interventions" also don't seem to have been involved.
If there is actual pain relief, it wouldn't be surprising if it somehow involves endorphins. And this is what the mouse experiment appears to show to be the case. In Mike Hall's words:
This strongly suggests that the pain relief observed in the previous experiment was the result of the release of endorphins. Endorphins that, in the second experiment, are prevented from working by the naloxone.
While this study is fascinating, it is far from a definitive (!) explanation of the placebo effect, or even how placebo effects mediate pain. It is a clear demonstration of classical, or Pavlovian, conditioning. Classical conditioning probably does account for some (!) of the placebo effects seen in some studies but many placebo effects, even for pain, have nothing at all to do with endorphins, naloxone, or conditioning.
Let's just say that what it has discovered is "classical, or Pavlovian, conditioning. Yes, OK, and so what?! If "classical conditioning probably does account for some of the placebo effects seen in some studies," so be it. But notice how he continues: "but many placebo effects, even for pain, have nothing at all to do with endorphins, naloxone, or conditioning"
And that's true: Many placebo effects are nothing but confounding factors, but the point here is that those confounding factors have been eliminated in this study as they should be. The new study is indeed less complicated by having eliminated confounding factors that are nothing but reporting errors, and Mike Hall is almost offended by this instead of praising it.
It sounds as if Mike Hall would very much like his old confounding factors to return, so he can continue to stress the complexity of the whole thing:
Either way, headlines claiming ‘researchers explain how the placebo effect works’ are not only reductive but imply a singular mechanism where none exists. Much of the public confusion surrounding the placebo effect is rooted in this persistent oversimplification, which glosses over what is a complex set of phenomena.
The conditioning observed in these mice is a specific mechanism that might contribute to some placebo responses, particularly those involving learned associations. However, it is just one part of a much larger, more intricate picture that includes other effects like regression to the mean, reporting biases, parallel interventions, and so on.
The interesting question remains: Is there such a thing as actual pain relief produced by the body? And the study appears to show that there is. But the discovery of endorphins is by no means a new discovery. The new discovery is 1) that it appears to influenced by conditioning, and 2) the part of the brain that produces the pain relief (possibly by means of increasing the level of endorphins) has been located.
What Mike Hall describes as "reductive" seems to be the actual strength of the new study. A study design that simplifies things has often accomplished (scientific) wonders: https://astrocamp.org/blog/gravity-experiment/Gravity Falling Experiment: Feather in a Vacuum!
Removing the effect of endorphins from the mouse experiment corresponds to removing gravity from the feather-in-a-vacuum experiment: 'Look, the feather doesn't fall at all!' All it shows is that the apparent pain relief has to do with the production of endorphins, which is no surprise but nevertheless an accomplishment.
Whether the whole thing works in a similar way in people as it appears to do in mice remains to be seen.
And it it is not as if we don't already have artificial endorphins. As Mike Hall puts it: "I would add that a single shot of morphine will offer more pain relief than endorphins are ever likely to manage alone."
I see you have missed the entire point of the article. Yes, I read it. I also listened to Mike's original analysis on the podcast. Did you?
Look at what the study says. Now look at the headline of, say, the New Scientist article, or Petrov's video. Heck, just search YouTube for the term "placebo effect" and you will find plenty more examples.
The study does not say that we have found out "how the placebo effect works", yet that is exactly how the articles and the YouTubes are presenting it. The study captured one mechanism of pain mitigation - classical conditioning causing the release of endorphins. What is referred to as "The placebo effect" is so much more than just that. But the media and the headlines make it out to be the ultimate piece of a puzzle that has now been solved, and resolved the entire question.
A recurring theme of Mike's ongoing analysis of the placebo effect, and in fact of the entire podcast, is how the media misrepresents science, and how when you get into it, the studies rarely say what the headlines say they say. It's irresponsible journalism and perpetuates misinformation.
It's a fascinating study, really, but it is far from definitively explaining how the placebo effect works.
No, I haven't listened to any podcast. Why would I? What are the important points it tells us about that the article does not mention? If it's relevant, you should tell us.
And if you read the whole thing, why didn't you comment on the part of the article that was actually relevant instead of the part of it that was a complaint about headlines?
The article isn't mainly about hyperbolic headlines. That's what the introduction to the article is about. The article itself is about the mouse study.
The problem with Mike Hall's article is the bias due to his "ongoing analysis of the placebo effect," which he (and you, too) seems to think is everything that is somehow supposed to be or has been interpreted as being part of the placebo effect, including all the confounding factors that are entirely different phenomena, such as "experimenter bias," which is obviously different from the object to be studied. Otherwise, it wouldn't be confounding.
This is also why my post distinguished between all the things that have erroneously been construed as part of the object to be studied, i.e. pain relief produced by the body (and brain) itself unlike whatever may have been interpreted as having been a part of the object but wasn't actually, i.e. "regression to the mean, experimenter bias, parallel interventions, classical conditioning, and more," except that conditioning may actually be an integral part of pain relief and not at all confounding.
Mike Hall seems to want to consider the object to be studied to be the whole shebang of pain relief produced by the body and all the confounding factors, whereas the new study eliminates those confounding factors. This has nothing at all to do with being reductive like the headlines, a theme that he returns to by the end of the article for some reason.
You repeat Mike Hall's idea that the new study is "fascinating," so why don't you tell us about that? What makes the study fascinating?
The article isn't mainly about hyperbolic headlines. That's what the introduction to the article is about. The article itself is about the mouse study.
The article is about media interpretation of scientific literature. You will notice that Mike has no problem with what the study concludes. He is not disputing it. He is not questioning it. He is reporting it accurately. But read this again:
Overly simplistic headlines muddy the water around placebo effects and mislead the public
The headline says what the article is about. The article is about overly simplistic headlines, and how they muddy the water around placebo effects and mislead the public.
The article is explicitly and directly about how the media misrepresents scientific papers for sensational headlines. That's what it's about. The mouse study happens to be a convenient recent example of that.
Mike's entire thesis regarding the placebo effect (that he has developed through years of reporting on the podcast, and which you can follow through all of his articles that I have linked to here on the forum) is that due to poor science communication and sensationalist headlines, the public at large has a vastly exaggerated idea of what the placebo effect is capable of. This article is another piece of that thesis.
This site uses cookies to help personalise content, tailor your experience and to keep you logged in if you register.
By continuing to use this site, you are consenting to our use of cookies.
