Wednesday, April 27, 2011
TedMed: The TED conference about health and medicine
If you love to watch fascinating people give talks that are cool, thought-provoking, inspiring, then you've got to watch the many wonderful people speak at the TED conference. Every year some of the most
Fantastic blog about science and skepticism
I just discovered a great blog by Dr. Steven Novella, a neurologist at Yale University School of Medicine. He produces a popular podcast called The Skeptics' Guide to the Universe, and also contributes to a number of other blogs that are devoted to the improving an understanding of science among the public.
A recent blog post of his recounts his experience appearing on the Dr. Oz show. Dr. Oz gained fame when he appeared regularly on the Oprah show. So popular was he on Oprah's program that he got his own spinoff. In this episode Oz asks "why are doctors afraid of alternative medicine?" Dr. Novella does an excellent job explaining that doctors are not afraid of anything and that the problem is that either quality scientific evidence is lacking, or that evidence is available and that it has shown that many "alternative" treatments, such as acupuncture, are no better than placebo. In response, Oz claims that Novella is being "dismissive" of the possibilities and then tells the audience that if "alternative treatments work for you, don't let anyone take that away from you."
I highly recommend Novella's blog. And here is the video of Novella's appearance on the Dr. Oz show.
A recent blog post of his recounts his experience appearing on the Dr. Oz show. Dr. Oz gained fame when he appeared regularly on the Oprah show. So popular was he on Oprah's program that he got his own spinoff. In this episode Oz asks "why are doctors afraid of alternative medicine?" Dr. Novella does an excellent job explaining that doctors are not afraid of anything and that the problem is that either quality scientific evidence is lacking, or that evidence is available and that it has shown that many "alternative" treatments, such as acupuncture, are no better than placebo. In response, Oz claims that Novella is being "dismissive" of the possibilities and then tells the audience that if "alternative treatments work for you, don't let anyone take that away from you."
I highly recommend Novella's blog. And here is the video of Novella's appearance on the Dr. Oz show.
Monday, April 18, 2011
It is natural to think that the world we perceive is a very close facsimile to objective reality, the way things really are. But this is perhaps one of the grandest of illusions. The fact is that our experience is constructed by the human brain. Our experience of our environment and of our body is essentially a simulation. But here's the thing -- the brain does not incorporate all
Observing pain related responses in others can impact our own pain perceptions
Although placebo analgesia is popularly believed to be prompted by taking a "sugar pill" (an inert substance that have no pharmacological effects) while being led to believe that it is an effective painkiller, there are actually many different ways of prompting the placebo response. These include verbal suggestions that induce expectations of efficacy (do these exercises and you'll feel better), conditioning (repeated exposure to a treatment and its effectiveness), etc.
But Luana Colloca and Fabrizio Benedetti, two very prominent researchers in the area placebo effects research recently published an intriguing study investigating social influences on placebo analgesia.
What they did was randomly assign participants to one of 3 groups: social observation, conditioning, and verbal suggestion.
In all groups, participants experience a series of electric shocks preceded by either a red or green light. The placebo part of the study is a sham electrode affixed to the middle finger, which participants are told delivers a nonpainful stimulation that has an analgesic effect; that is it can reduce the pain of the shocks. The green light is supposed to indicate that this analgesic stimulus has been turned on and that reduced pain should be anticipated.
Now, in the social observation group, participants learn from watching a "demonstrator" go through the series of trials first, that the green light precedes diminished pain relative to red light trials. They can see this because they can see the demonstrator rate the painfulness each pain shock, and they can see that he always rates green trials as less painful than red trials. Subsequent to this "simulation" phase, participants receive a series of red and green-associated pain stimuli in the same way as the demonstrator. In fact green light stimuli were set to be equally painful to red light stimuli.
In the conditioning group, participants are informed that the green and red lights indicate the activation and deactivation, respectively, of the electrode on the middle finger and then are given a series of shocks. To condition the analgesic effect associated with the green light, the shock intensity was surreptitiously lowered. Thus, while participants were led to believe that the electrode affixed to their middle finger was being activated during green light trials and that it was this activation that had an analgesic effect, the electrode was not activated at all and instead, the shock intensity was lowered. After this conditioning phase, a testing period begun whereby the stimulus intensity of green light trials was raised to the same level as red light trials.
In the verbal suggestion group, participants were simply informed that the green light would signal the activation of the analgesic electrode while the red light would indicate its inactivation. In fact, all stimuli were equally painful as in the testing phase of the other conditions.
So what did they find? Well, Colloca and Benedetti were not surprised to find that the conditioning group exhibited a placebo effect as they had shown this effect in a previous study. The unique and truly cool finding here is that participants did not need to experience this conditioning first hand. It was sufficient to merely observe another person undergoing a beneficial effect of a treatment (the "analgesic" electrode). Indeed the magnitude of the placebo responses induced through observational learning was similar to the placebo responses induced through the direct experience of a conditioning procedure.
But that's not all. Another intriguing finding was that the amount of pain reduction exhibited in response to green trials compared to red trials was significantly correlated with how high participants scored on a measure of empathy. So the stronger one's empathic ability, the stronger was the placebo effect following social observation. Why do I find this so fascinating? I'll tell you about it in an upcoming blog post.
In the meantime, do check out this fascinating piece of research for yourself.
Colloca, L & Benedetti, F (2009). Placebo analgesia induced by social observational learning. Pain, 144 (1-2), pp. 28-34.
But Luana Colloca and Fabrizio Benedetti, two very prominent researchers in the area placebo effects research recently published an intriguing study investigating social influences on placebo analgesia.
What they did was randomly assign participants to one of 3 groups: social observation, conditioning, and verbal suggestion.
In all groups, participants experience a series of electric shocks preceded by either a red or green light. The placebo part of the study is a sham electrode affixed to the middle finger, which participants are told delivers a nonpainful stimulation that has an analgesic effect; that is it can reduce the pain of the shocks. The green light is supposed to indicate that this analgesic stimulus has been turned on and that reduced pain should be anticipated.
Now, in the social observation group, participants learn from watching a "demonstrator" go through the series of trials first, that the green light precedes diminished pain relative to red light trials. They can see this because they can see the demonstrator rate the painfulness each pain shock, and they can see that he always rates green trials as less painful than red trials. Subsequent to this "simulation" phase, participants receive a series of red and green-associated pain stimuli in the same way as the demonstrator. In fact green light stimuli were set to be equally painful to red light stimuli.
In the verbal suggestion group, participants were simply informed that the green light would signal the activation of the analgesic electrode while the red light would indicate its inactivation. In fact, all stimuli were equally painful as in the testing phase of the other conditions.
So what did they find? Well, Colloca and Benedetti were not surprised to find that the conditioning group exhibited a placebo effect as they had shown this effect in a previous study. The unique and truly cool finding here is that participants did not need to experience this conditioning first hand. It was sufficient to merely observe another person undergoing a beneficial effect of a treatment (the "analgesic" electrode). Indeed the magnitude of the placebo responses induced through observational learning was similar to the placebo responses induced through the direct experience of a conditioning procedure.
But that's not all. Another intriguing finding was that the amount of pain reduction exhibited in response to green trials compared to red trials was significantly correlated with how high participants scored on a measure of empathy. So the stronger one's empathic ability, the stronger was the placebo effect following social observation. Why do I find this so fascinating? I'll tell you about it in an upcoming blog post.
In the meantime, do check out this fascinating piece of research for yourself.
Colloca, L & Benedetti, F (2009). Placebo analgesia induced by social observational learning. Pain, 144 (1-2), pp. 28-34.
What is a placebo?
I've seen so many attempts at defining a placebo. The most common is that it is "an inert substance", a "sugar pill". This definition has become popular because historically most discussion surrounding the placebo effect pertained to the use of "placebo" groups in drug trials. In this case, subjects were randomly assigned to receive either an experimental drug with some pharmacological agent(s) being tested or to receive a placebo, a pill that looked, felt, and smelled the same as the active one but which was minus the pharmacological agent(s). This methodology reflected the recognition that people will improve on some outcome for a variety of reasons having nothing to do with the drug being tested.
Say Pfizer is testing a new analgesic for arthritis pain. They set up a clinical trial and assign half to receive their new drug and half to receive an inert counterpart, a "placebo". Participants keep diaries of their pain for a week before taking their pills (so a baseline can be established), then take begin taking their assigned pills. After a month, all the data are collected and analyzed and it is found that indeed those in the active drug group improved, they felt less pain under the influence of the pill compared to their baseline period. But so did the "placebo" group! How can this be? How can people suffering from real pain experience relief from nothing?
The answer is that any or all of several phenomena can occur concomitant with the administration of a "placebo" to cause improvement.
1. Spontaneous remission. This means that any condition can improve on its own, without any intervention. There can be many reasons for this: during the period weather conditions may have become more favorable, lessening pain for all. All chronic medical conditions, including pain, have periods in which symptoms wax and wane.
2. Regression to the mean. Clinical trials of drugs (and other treatments/therapies) tend to seek participants whose pain is especially bad, longstanding, etc. Additionally, people tend to seek out and agree to participating in clinical trials when pain is at its worst. But pain is not always at its worst. Pain varies around some average (i.e., the "mean"). Sometimes it's worse than average; other times it's better than average. Beginning a clinical trial when pain is worse than average, means that it is likely that pain will begin to slide back toward the average (i.e., improve) for no other reason than the natural ups and downs of pain.
3. Detection ambiguity. On a scale of 0 (no pain at all) to 10 (worst pain imaginable), please rate your pain. Sound simple and straightforward, right? Well, not necessarily. Pain is highly subjective. Diabetes, cardiovascular disease, and cancer all have established objective indices that can objectively quantify their state. For example, a simple pin-prick blood test can produce a index of blood glucose, which is a reliable indicator of the presence of diabetes and of how well it is being managed. But pain has no such measure; it is inherently a subjective phenomenon and so we must rely mainly on people's reports of their pain. This is all well and fine but there is ambiguity in how we feel.
Now, imagine that you are led to believe that you have been given a powerful painkiller and then asked to rate your pain on that 0 to 10 scale. Believing you received an analgesic may prime your attention toward the detection of evidence of reduced pain. Pain naturally waxes and wanes. Before participation in the drug trial, you might have interpreted the waning of pain for what it is -- a valley in an unending series of hills and valleys. But because you are concomitantly taking what what you believe is an analgesic there is a greater likelihood that you will interpret the waning of pain as evidence that that the drug is working.
Also, detecting pain in the body is a bit like detecting the temperature outside. Numerous factors can influence your perception of temperature: humidity, wind, how sunny it is, your own mood and anxiety level, etc. We might say that the influence of all these factors leads to ambiguity in detecting the temperature. An implication of this ambiguity is that your estimate of temperature can be manipulated by getting you to focus on some of these factors more than others, which is essentially what drug trials can do.
4. Placebo response. The placebo response is that
So clinical trials of drugs must show that a drug produces improvements that are over and above
Say Pfizer is testing a new analgesic for arthritis pain. They set up a clinical trial and assign half to receive their new drug and half to receive an inert counterpart, a "placebo". Participants keep diaries of their pain for a week before taking their pills (so a baseline can be established), then take begin taking their assigned pills. After a month, all the data are collected and analyzed and it is found that indeed those in the active drug group improved, they felt less pain under the influence of the pill compared to their baseline period. But so did the "placebo" group! How can this be? How can people suffering from real pain experience relief from nothing?
The answer is that any or all of several phenomena can occur concomitant with the administration of a "placebo" to cause improvement.
1. Spontaneous remission. This means that any condition can improve on its own, without any intervention. There can be many reasons for this: during the period weather conditions may have become more favorable, lessening pain for all. All chronic medical conditions, including pain, have periods in which symptoms wax and wane.
2. Regression to the mean. Clinical trials of drugs (and other treatments/therapies) tend to seek participants whose pain is especially bad, longstanding, etc. Additionally, people tend to seek out and agree to participating in clinical trials when pain is at its worst. But pain is not always at its worst. Pain varies around some average (i.e., the "mean"). Sometimes it's worse than average; other times it's better than average. Beginning a clinical trial when pain is worse than average, means that it is likely that pain will begin to slide back toward the average (i.e., improve) for no other reason than the natural ups and downs of pain.
3. Detection ambiguity. On a scale of 0 (no pain at all) to 10 (worst pain imaginable), please rate your pain. Sound simple and straightforward, right? Well, not necessarily. Pain is highly subjective. Diabetes, cardiovascular disease, and cancer all have established objective indices that can objectively quantify their state. For example, a simple pin-prick blood test can produce a index of blood glucose, which is a reliable indicator of the presence of diabetes and of how well it is being managed. But pain has no such measure; it is inherently a subjective phenomenon and so we must rely mainly on people's reports of their pain. This is all well and fine but there is ambiguity in how we feel.
Now, imagine that you are led to believe that you have been given a powerful painkiller and then asked to rate your pain on that 0 to 10 scale. Believing you received an analgesic may prime your attention toward the detection of evidence of reduced pain. Pain naturally waxes and wanes. Before participation in the drug trial, you might have interpreted the waning of pain for what it is -- a valley in an unending series of hills and valleys. But because you are concomitantly taking what what you believe is an analgesic there is a greater likelihood that you will interpret the waning of pain as evidence that that the drug is working.
Also, detecting pain in the body is a bit like detecting the temperature outside. Numerous factors can influence your perception of temperature: humidity, wind, how sunny it is, your own mood and anxiety level, etc. We might say that the influence of all these factors leads to ambiguity in detecting the temperature. An implication of this ambiguity is that your estimate of temperature can be manipulated by getting you to focus on some of these factors more than others, which is essentially what drug trials can do.
4. Placebo response. The placebo response is that
So clinical trials of drugs must show that a drug produces improvements that are over and above
Objectively measuring pain
Pain is an inherently private, subjective phenomenon. There is, at the present time, simply no blood test, or even brain scan that can objectively quantify pain. This fact makes it tough on both pain patients as well as pain clinicians.
The subjective nature of pain is tough for patients because it means that their pain is often dismissed. The patient cannot point to a test result proving that the severity of the pain that they claim is "real". One chronic pain patient I met told me that she was regularly "punished" for her extraordinary coping efforts because the more effectively she coped, the less she appeared to be in pain, the less concern, attention, and patience she received from others around her who interpreted her coping as an indication that she was in less pain. This really is a terrible problem for people with chronic pain and can add to their suffering considerably.
The subjective nature of pain is tough for clinicians because it is difficult to determine the efficacy of their treatments. First, two individuals may rate their pain as 7 on a 0 to 10 scale, but that doesn't mean they their pain experience is equal. This may be because of differences in past experience; that is ratings are relative to each individual's extreme experiences. Patient A may be in excruciating pain that patient B would rate as a 9 or 10, but because Patient A has experienced even worse pain, to her, the pain is perceived at about 7 out of 10. Second, there may be differences in patient motivations. Some individuals may use opportunities to rate their pain as a means of expressing their suffering. They might really feel more like a 5 or 6 but boost it a notch as a means of communicating that they're feeling a great deal of hurt.
There exist several subjective pain scales. The most popular are...
Numeric Rating Scale
Visual Analog Scale
Category Intensity Scale
Faces Scale
Wong et al (1995)
The subjective nature of pain is tough for patients because it means that their pain is often dismissed. The patient cannot point to a test result proving that the severity of the pain that they claim is "real". One chronic pain patient I met told me that she was regularly "punished" for her extraordinary coping efforts because the more effectively she coped, the less she appeared to be in pain, the less concern, attention, and patience she received from others around her who interpreted her coping as an indication that she was in less pain. This really is a terrible problem for people with chronic pain and can add to their suffering considerably.
The subjective nature of pain is tough for clinicians because it is difficult to determine the efficacy of their treatments. First, two individuals may rate their pain as 7 on a 0 to 10 scale, but that doesn't mean they their pain experience is equal. This may be because of differences in past experience; that is ratings are relative to each individual's extreme experiences. Patient A may be in excruciating pain that patient B would rate as a 9 or 10, but because Patient A has experienced even worse pain, to her, the pain is perceived at about 7 out of 10. Second, there may be differences in patient motivations. Some individuals may use opportunities to rate their pain as a means of expressing their suffering. They might really feel more like a 5 or 6 but boost it a notch as a means of communicating that they're feeling a great deal of hurt.
There exist several subjective pain scales. The most popular are...
Numeric Rating Scale
Visual Analog Scale
Category Intensity Scale
Faces Scale
Wong et al (1995)
Wong-Baker FACES Pain Rating Scale. Note: From Wong, D.: Whaley and Wong's Nursing Care of Infants and Children, ed 5, 1995, p. 1085. Copyrighted by Mosby-Year Book, Inc.
Observing someone modeling pain tolerant behavior can influence one's own perception of pain
Social factors have been shown in dozens if not hundreds of studies to have widespread and profound effects on numerous health outcomes. For example, people who are isolated tend to live shorter and less happy lives, and knowing others are available for social support can buffer us against the ravages of everyday stresses in life and decrease the risk of cardiovascular disease, diabetes and other conditions. Given this immense influence of social relationships on so many aspects of health, it has been surprising to me that there has been relatively little research exploring the impact of social factors on pain!
Indeed, I think this topic is so important that I chose to make it the topic of my Ph.D. dissertation.
In the process of becoming familiar with the scientific literature, it occurred to me that one way in which one's social environment might influence pain is through social modeling. That is, the degree to which people would find some experience painful would depend on the responses of others in their social environment. In other words, after watching someone stoically absorb painful shocks you would feel less pain from those shocks than if you had just observed someone responding more weakly to the pain stimuli.
In the 1970s, psychologist Albert Bandura, developed what has become known as social learning theory. The essence of social learning theory is that people can learn new responses through observing others in lieu of direct experience. Bandura, in his 1977 book said, "Learning would be exceedingly laborious, not to mention hazardous, if people had to rely solely on the effects of their own actions to inform them what to do. Fortunately, most human behavior is learned observationally through modeling"
I thought this was pretty straightforward stuff so when I hit the literature I expected to find lots of studies looking at social modeling and pain. I was surprised to learn that I would have to go all the way back to 1976 and a paper written by Kenneth Craig and presented at an American Psychological Association meeting.
Here's how it went...
In the process of becoming familiar with the scientific literature, it occurred to me that one way in which one's social environment might influence pain is through social modeling. That is, the degree to which people would find some experience painful would depend on the responses of others in their social environment. In other words, after watching someone stoically absorb painful shocks you would feel less pain from those shocks than if you had just observed someone responding more weakly to the pain stimuli.
In the 1970s, psychologist Albert Bandura, developed what has become known as social learning theory. The essence of social learning theory is that people can learn new responses through observing others in lieu of direct experience. Bandura, in his 1977 book said, "Learning would be exceedingly laborious, not to mention hazardous, if people had to rely solely on the effects of their own actions to inform them what to do. Fortunately, most human behavior is learned observationally through modeling"
I thought this was pretty straightforward stuff so when I hit the literature I expected to find lots of studies looking at social modeling and pain. I was surprised to learn that I would have to go all the way back to 1976 and a paper written by Kenneth Craig and presented at an American Psychological Association meeting.
Here's how it went...
A great video on the placebo effect
Check out this video on the placebo effect, an excerpt from the documentary "Alternative Medicine - The Evidence"...
You can check out more info on the BBC's "Alternative Medicine" series by following this link: http://www.open2.net/alternativemedicine/index.html
You can check out more info on the BBC's "Alternative Medicine" series by following this link: http://www.open2.net/alternativemedicine/index.html
Hilarious demonstration of the Placebo Effect by Penn & Teller
For a wonderful and hilarious demonstration of the placebo effect, check out this video from the geniuses of magic, Penn & Teller. To be fair, though, they probably chose to include the most susceptible people from among all they recorded, but it does nonetheless demonstrate the remarkable power of suggestion.
More frequent treatment improves rate of healing of duodenal ulcers. But the treatment is a placebo!!
I just came across this study. It was published back in 1999 but it's kind of cool so I thought I'd share it with you.
de Craen et al (1999) performed a review of 79 duodenal ulcer clinical trials that administered either a 2-times daily or a 4-times daily treatment regimen. The interesting thing is that the researchers looked specifically not at active duodenal ulcer treatments but rather at placebo treatments.
When they pooled the data from all 79 studies they found that the 4 week healing rate of the trials employing a 2-times daily regimen was 36.2%, but was 44.2% for trials employing a 4-times daily regimen! Thus, treatment 4 times daily was more effective than treatment 2 times daily. But these were placebos, inactive treatments. Dose shouldn't make a difference with pharmacologically inert placebos. Yet, it did. This is a fascinating result -- not only can placebos prompt healing of duodenal ulcers (which is amazing in an of itself) but higher doses, provoke greater healing rates!!
De Craen et al. (1999). Placebo effect in the treatment of duodenal ulcer. British journal of clinical pharmacology, 48 (6), 853-860.
de Craen et al (1999) performed a review of 79 duodenal ulcer clinical trials that administered either a 2-times daily or a 4-times daily treatment regimen. The interesting thing is that the researchers looked specifically not at active duodenal ulcer treatments but rather at placebo treatments.
When they pooled the data from all 79 studies they found that the 4 week healing rate of the trials employing a 2-times daily regimen was 36.2%, but was 44.2% for trials employing a 4-times daily regimen! Thus, treatment 4 times daily was more effective than treatment 2 times daily. But these were placebos, inactive treatments. Dose shouldn't make a difference with pharmacologically inert placebos. Yet, it did. This is a fascinating result -- not only can placebos prompt healing of duodenal ulcers (which is amazing in an of itself) but higher doses, provoke greater healing rates!!
De Craen et al. (1999). Placebo effect in the treatment of duodenal ulcer. British journal of clinical pharmacology, 48 (6), 853-860.
Effectiveness of arthroscopic knee surgery one big placebo response?
Here's a video about the amazing study conducted by Bruce Moseley at Baylor College of Medicine in Houston. He performed standard arthroscopic knee surgery on one group of patients, while in another group, he performed a “sham surgery” — he only made 3 incisions and made all the motions of the real surgery but in fact did nothing else. The sham (placebo) surgery was just as effective at improving pain and function as the real thing. Now, it is definitely premature to say that the benefits of other surgeries are essentially placebos responses, but it does make the point very clear that we must explicitly ascertain what portion of the benefit of a surgery amounts to a placebo response.
The Placebo Effect - Knee Surgery
The Placebo Effect - Knee Surgery
Is it possible that placebo effects are merely the result of biasing attention towards signs of improvement?
Well known doc decked out in white lab coat, in famous pain clinic hands you a packet of pills and says with confidence that the medicine he is giving you is a potent painkiller and that you should feel less pain shortly after taking it. You take the pill when you get home. Sure enough, your pain eases considerably. You really do feel less pain. Thank goodness, you think, for the existence of such wonderful analgesics.
Yes, analgesics are indeed wonderful, but you didn't get one. The pills the doctor gave you contained only starch. You got a placebo. "But I really did feel less pain," you protest. Absolutely, but it wasn't because of anything in the pill itself. So how on earth did this placebo work to quell your pain? Well, placebo researchers would say that the confident doctor and clinical context promoted a strong expectation of analgesia and it is this expectation that prompted the brain to release endogenous (within the body) painkilling substances such as opioids. This may be. Indeed, many studies have shown that when drugs that block the action of opioids are administered immediately subsequent to placebos, analgesia does not occur. But a huge mystery remains: how does a mere expectation (no matter how strong or confident) lead to the complex neurophysiological activity associated with analgesia? Put another way, how exactly does expectation "turn on" the brain's built-in analgesic systems? If expectation can induce analgesia, why can't we merely "will ourselves" to feel less pain?
Here's another scenario: You're in the hospital. Everyday a nurse comes to your room and gives you a shot of morphine. Shortly afterwards you feel your pain ease. This repeats multiple times a day over a series of days. But then one day the nurse plays a trick on you. Without your knowing it she substitutes saline for the morphine. Shortly afterwards your pain eases. Thank goodness, you think, for morphine.
But once again, we are left with a mystery. How is it possible that to feel less pain when you received nothing more than salt water? Is morphine one big placebo effect? Is it a scam? No, morphine is truly a powerful painkiller. Placebo researchers would say that in this case, the repeated pairing of morphine with subsequent pain relief conditioned your nervous system to predict/expect pain relief much as dogs learn to salivate at the sound of a bell following multiple pairings of a bell followed by food. So this conditioning is somewhat similar to the situation in which your are led to the expectation of pain relief through verbal suggestion by a doctor. The difference is that in the case of conditioning, you are not just given a suggestion, you actually learn from experience that A (injection of drug) leads to B (pain relief).
But again, the mystery remains: how on earth can conditioning produce pain relief? You see, during the conditioning (learning) phase, you're actually receiving a painkiller (e.g., morphine) so it is the specific pharmacological action of the drug that is producing the analgesic effect. Then you're given a saline solution, yet you still feel less pain. How is this possible in the absence of the drug? It makes one wonder whether it was the drug that was relieving pain after a few administrations.
So the exact mechanisms underlying these two methods of provoking placebo effects remain a mystery.
Just because it's a mystery doesn't mean there aren't any theories out there.
One particularly interesting one suggests that the placebo effect is nothing more than an issue of signal detection. What the heck does that mean?
I'd like to use a great analogy introduced by Lorraine Allan and Shepard Siegel (2002) in their interesting paper on the application of signal detection theory for understanding placebo effects. Suppose that you're a physician and a patient presents with abdominal pains. You need to diagnose the cause of the symptoms. So you perform a physical exam, order blood tests, x-rays and an ultrasound. The task before the you is to identify a diagnosis that best fits the evidence. You suspect appendicitis. There are 4 possible outcomes:
| Decision | ||
| Operate | Do not operate | |
| Appendicitis | Correct positive | False rejection |
| No appendicitis | False positive | Correct rejection |
- The patient has appendicitis and you choose to operate (correct positive).
- The patient has appendicitis but you fail to detect it and therefore do not operate (false rejection).
- The patient does not have appendicitis, yet to believe you've detected and therefore operate (false positive).
- The patient does not have appendicitis and you reject the possibility of appendicitis, and therefore do not operate (correct rejection).
So, there are two ways that you could be right: the signal (appendicitis) could be present amid the noise and you are able to detect it or the signal could be absent (no appendicitis) and you correctly conclude it is not there.
In a situation in which the evidence is unambiguous and a diagnosis is clear, it is easy to conclude correctly whether a signal is present or not. But most real life situations are filled with ambiguity. In this situation, it is quite possible to make an error. So in making your diagnosis you must decide which of the two errors is the worst evil. Is it better to mistakenly identify a signal (false positive) or miss the presence of a signal (false rejection). I would hazard a guess that most doctors would say the latter is the worst of the two evils and so they would adopt a "liberal" criterion.
Well let's say you decide the patient has appendicitis and you perform an appendectomy. During surgery no evidence of appendicitis is found. The patient apparently suffers from some other condition with indications that are similar to appendicitis. You made a false positive error -- you decided that a signal (infected appendix) was present amid the ambiguous information, when in fact it wasn't.
Since it has been determined that appendicitis is not the cause of the symptoms, you give the patient medication to provide symptomatic relief. Now the patient faces a task that is actually quite similar to the physician. The patient does not feel the same level of pain or types of sensations all the time. Signals from the body are ambiguous just as there was ambiguity in the information available to the physician. Yet, like the physician, the patient must detect a signal (attenuation of abdominal pain) is present amid the context of noise (variable levels of pain and other sensations over time). The patient reports a decrease in pain.
But this patient has been given a placebo -- a pill with no active ingredient. In effect the patient applied a liberal criterion, as you did. Was your patient highly suggestible, gullible? No. As Allan and Siegel (2002) put it,
"The patient's mistake is as understandable as the physician's mistake. Both are inevitable results of deciding on the presence or absence of an ambiguous signal. In the case of the physician, the mistake is called a false positive. In the case of the patient, the mistake is called a placebo effect." (Allan & Siegel, 2002, p. 415).
In essence, signal detection theory states that placebo effects can arise because of a search for signs amongst a noisy information that a treatment is working can lead to the misidentification of improvement when it has in fact not occurred.
Interesting, eh?
Although placebo analgesia is popularly believed to be prompted by taking a "sugar pill" (an inert substance that have no pharmacological effects) while being led to believe that it is an effective painkiller, there are actually many different ways of prompting the placebo response. These include verbal suggestions that induce expectations of efficacy (do these exercises and you'll feel better), conditioning (repeated exposure to a treatment and its effectiveness), etc.
But Luana Colloca and Fabrizio Benedetti, two very prominent researchers in the area placebo effects research recently published an intriguing study investigating social influences on placebo analgesia.
What they did was randomly assign participants to one of 3 groups: social observation, conditioning, and verbal suggestion.
In all groups, participants experience a series of electric shocks preceded by either a red or green light. The placebo part of the study is a sham electrode affixed to the middle finger, which participants are told delivers a nonpainful stimulation that has an analgesic effect; that is it can reduce the pain of the shocks. The green light is supposed to indicate that this analgesic stimulus has been turned on and that reduced pain should be anticipated.
Now, in the social observation group, participants learn from watching a "demonstrator" go through the series of trials first, that the green light precedes diminished pain relative to red light trials. They can see this because they can see the demonstrator rate the painfulness each pain shock.
But Luana Colloca and Fabrizio Benedetti, two very prominent researchers in the area placebo effects research recently published an intriguing study investigating social influences on placebo analgesia.
What they did was randomly assign participants to one of 3 groups: social observation, conditioning, and verbal suggestion.
In all groups, participants experience a series of electric shocks preceded by either a red or green light. The placebo part of the study is a sham electrode affixed to the middle finger, which participants are told delivers a nonpainful stimulation that has an analgesic effect; that is it can reduce the pain of the shocks. The green light is supposed to indicate that this analgesic stimulus has been turned on and that reduced pain should be anticipated.
Now, in the social observation group, participants learn from watching a "demonstrator" go through the series of trials first, that the green light precedes diminished pain relative to red light trials. They can see this because they can see the demonstrator rate the painfulness each pain shock.
Here's a dilemma for you...
You are a physician who is treating a patient suffering from chronic pain. The patient has been on morphine but is still experiencing difficult pain. You can increase the dose but high doses of morphine introduce side effects that may not be tolerable, including constipation, respiratory depression, headaches and nausea. What should you do?
Well, a recent survey (Tilburt, et al, 2008) of 334 active internists and 345 rheumatologists in the U.S. found that doctors currently make considerable use of placebos. Here's a highlight of some of their findings:
And how did these physicians describe the placebo treatments they recommended to their patients?
So, at least in this sample of physicians, most would prescribe a "sugar pill" for patients with chronic pain if there was evidence of their efficacy over no treatment. In other words, most physicians regard the therapeutic impact of placebos to be legitimate. "If they work, at least for some patients, why not?" seems to be the thinking.
The other interesting finding from this study is the use of "active" placebos -- innocuous treatments such as vitamins and over-the-counter analgesics. I think this is interesting because it somewhat sidesteps the deception issue that tends to stand as a barrier to the clinical exploitation of the placebo effect. Doctors can honestly say that these treatments help many people to feel better.
In sum, it appears that most docs believe that recommending placebo treatments to be ethically permissible but there is a definite preference for "active" placebos in which there is some degree (even if small) chance of a beneficial pharmacological effect, or at least promote a sense in the patient that the doctor is taking care of the patient and also of being able to take some control of one's condition.
So as the debate seems to rage on about whether to use placebos in clinical practice, it appears that they are very much alive and well and at work in a remarkable number of doctors' offices!
Tilburt et al. (2008). Prescribing "placebo treatments": results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938.
You are a physician who is treating a patient suffering from chronic pain. The patient has been on morphine but is still experiencing difficult pain. You can increase the dose but high doses of morphine introduce side effects that may not be tolerable, including constipation, respiratory depression, headaches and nausea. What should you do?
Well, a recent survey (Tilburt, et al, 2008) of 334 active internists and 345 rheumatologists in the U.S. found that doctors currently make considerable use of placebos. Here's a highlight of some of their findings:
- 58% said they would be very or moderately likely to give a dextrose pill to a patient with fibromyalgia if trials had shown placebos to be superior to no treatment.
- 62% believed that recommending such treatments was ethically permissible or even obligatory.
- 55% reported recommending at least one placebo treatment over the past year. These include so-called "active" placebos, such as over-the counter analgesics (41%), vitamins (38%), antibiotics (13%), and sedatives (13%). Only 2% recommended entirely inactive placebos ("sugar pills").
And how did these physicians describe the placebo treatments they recommended to their patients?
- 68% of those who recommend placebo treatments said they typically describe them as "a medicine not typically used for your condition but might benefit you."
- 18% described placebo treatments as a "medicine"
- 5% actually revealed the treatment as "a placebo".
So, at least in this sample of physicians, most would prescribe a "sugar pill" for patients with chronic pain if there was evidence of their efficacy over no treatment. In other words, most physicians regard the therapeutic impact of placebos to be legitimate. "If they work, at least for some patients, why not?" seems to be the thinking.
The other interesting finding from this study is the use of "active" placebos -- innocuous treatments such as vitamins and over-the-counter analgesics. I think this is interesting because it somewhat sidesteps the deception issue that tends to stand as a barrier to the clinical exploitation of the placebo effect. Doctors can honestly say that these treatments help many people to feel better.
In sum, it appears that most docs believe that recommending placebo treatments to be ethically permissible but there is a definite preference for "active" placebos in which there is some degree (even if small) chance of a beneficial pharmacological effect, or at least promote a sense in the patient that the doctor is taking care of the patient and also of being able to take some control of one's condition.
So as the debate seems to rage on about whether to use placebos in clinical practice, it appears that they are very much alive and well and at work in a remarkable number of doctors' offices!
Tilburt et al. (2008). Prescribing "placebo treatments": results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938.
Inhibiting activity of the hormone Cholecystokinin can boost the placebo response!
The placebo response is a wonderful demonstration of the potential of the mind to bring about almost magical healing powers. But though there has been an amazing surge of knowledge about the placebo response over the last several years, there is still much we don’t know, and I think the most exciting times are yet to come. Here are some of the questions I think are particularly interesting, mainly because their answers have important clinical implications.
Not everyone is a “placebo responder”. Why? Perhaps we’ve been looking at this question the wrong way. We’ve been asking, “what makes a placebo responder?” The answer to this question has proven elusive. Perhaps we should be asking, “what prevents someone from being a placebo responder?” We actually already have one answer to this latter question. A fascinating study by Benedetti et al (1995) has shown that Cholecystokinin(CCK) acts to limit placebo responses. When given a CCK antagonist (e.g., proglumide) a considerably larger placebo response occurs. So CCK limits the placebo response and a drug that removes CCK from the picture, removes this limit. For this reason, the CCK antagonist proglumide has been called a “placebo amplifier”.
The CCK discovery is a fascinating one but the question of what limits the placebo is far from fully answered. CCK cannot turn non-placebo responders into responders. Nonetheless, thinking in terms of what may be limiting endogenous pain inhibition mechanisms and blocking these inhibitors provide some fruitful avenues in our efforts to harness the body's own built-in therapeutic capabilities.
Not everyone is a “placebo responder”. Why? Perhaps we’ve been looking at this question the wrong way. We’ve been asking, “what makes a placebo responder?” The answer to this question has proven elusive. Perhaps we should be asking, “what prevents someone from being a placebo responder?” We actually already have one answer to this latter question. A fascinating study by Benedetti et al (1995) has shown that Cholecystokinin(CCK) acts to limit placebo responses. When given a CCK antagonist (e.g., proglumide) a considerably larger placebo response occurs. So CCK limits the placebo response and a drug that removes CCK from the picture, removes this limit. For this reason, the CCK antagonist proglumide has been called a “placebo amplifier”.
The CCK discovery is a fascinating one but the question of what limits the placebo is far from fully answered. CCK cannot turn non-placebo responders into responders. Nonetheless, thinking in terms of what may be limiting endogenous pain inhibition mechanisms and blocking these inhibitors provide some fruitful avenues in our efforts to harness the body's own built-in therapeutic capabilities.
Preamputation Mirror Therapy May Prevent Development of Phantom Limb Pain
Mirror therapy has been effectively employed to treat majority of the 72 % of amputees with phantom limb syndrome, suffering from both non-painful and painful sensations. Mirror therapy involves patients placing their intact limb into one side of a box divided by a mirror. This mirror is placed in a way that when viewed slightly off center, allows patients to perceive themselves as having 2 intact limbs. Having this perception, patients perform a series of movement exercises with the intact arm. Then, as unscientific as it may sound, the pain vanishes. The question remained that, if mirror therapy can treat phantom limb pain, couldn’t it be used to prevent it from occurring before hand? They conducted a 4 case study involving 4 male patients in their early to late twenties who had previously experienced various traumatic injuries that rendered their limbs inoperative. To test this connection in possibly preventing phantom limb pain, all patients underwent 14 sessions of mirror therapy before their amputations. The follow ups of 1 month after each patient’s surgery revealed moderate to no phantom limb pain. Those who experienced moderate phantom limb pain expressed that they were tolerable and did not hamper their quality of life. Noticing the varied outcomes, the researchers reflected that the length of the mirror therapy sessions should be prolonged according to patients and their conditions. The mechanism behind the effects of mirror therapy on phantom limb pain is still a mystery in the field of psychology. However, with up coming studies, even a small contribution of knowledge in the ability to prevent phantom limb pain can have a dramatic impact on the public, the amputees themselves, and future research.
Hanling, Steven R. MD; Wallace, Scott C. MD; Hollenbeck, Kerry J. MD; Belnap, Brian D. DO; Tulis, Matthew R. MD. Anesthesia & Analgesia (February 2010), 110(2),pg 611-614
Hanling, Steven R. MD; Wallace, Scott C. MD; Hollenbeck, Kerry J. MD; Belnap, Brian D. DO; Tulis, Matthew R. MD. Anesthesia & Analgesia (February 2010), 110(2),pg 611-614
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