No, No, Nocebo
Can the way we approach pain actually make it worse?
This post will look first and foremost at the relation between the placebo and nocebo effects, what it means for your health and pain, and how we can lessen the negative effects. The nocebo effect can have a significant input into prolonged pain, but what does it actually mean and how do we change it? We'll look into that in more detail so that hopefully after you've read this you will be able to:
Identify the difference between the placebo and nocebo effect;
Understand how it can impact your pain;
Take steps to minimise those effects;
Better understand how you can reduce the way you contribute to the nocebo effect in others.
Have you ever thought much about your expectations affect your outcomes?
Is it possible if you think you will improve, or are worried that you won't, it will change the way your body reacts?
I had something of a situation like this with a patient I met a little while back. It reminded me of the power of nocebo when it comes to therapy.
Before getting into that, we should probably take a moment to look at what nocebo actually is.
And if we are going to look at nocebo, we probably need to discuss placebo. Have a bit of a look at the yin to the yang, light to dark and that sort of thing.
And by placebo, I don't mean the English rock band either, I mean the actual placebo effect, from which they likely got their name.
A placebo is essentially a treatment with no therapeutic effect. This means that it does not actually affect a person physiologically, it doesn't make any direct changes. The placebo effect is when this treatment, which has no therapeutic effect (or active ingredient, if we are talking about medication), still produces an improvement in a patient's condition.
So essentially it's a treatment which shouldn't really have any effect, but nevertheless still seems to.
But, hey, as long as it works, right?
If we look at an example of this, we only need to take a look at research. In pharmaceutical research for example, they would normally split participants into two groups. One group may be provided with an active medication, then a second group, the control group, would be provided with an identical looking medication containing no active ingredient (such as a sugar pill). Neither group is told which is which, with the idea being that if there is no influence of patient expectations, they will be able to determine if any improvement is solely due to the active ingredient in the medication.
In some instances, those in the second group may experience an improvement in their condition or symptoms. Sometimes it's the same as the active medication, occasionally it's more. Often this is because of the persons expectations of an improvement from the medication actually creating an improvement. This is the placebo effect(1).
It's probably a fairly good statement on how powerful the brain is in health (rather than sugar pills being a miracle cure).
Now that's medications, but what about other things?
It can apply to many different therapeutic treatments.
When it comes to pain, how do you think your expectation of how manipulation, or mobilisation, or massage might affect the way you respond to those treatments?
If you've had good results with a particular therapist in the past, is it likely that you will also have good results the next time you see them because you trust them and expect them to be able to help you? It's certainly not the only reason you might get some improvement, but it has an impact(2).
There are stories of people having therapeutic ultrasound and reporting increased warmth and decreased pain, despite the fact the therapist has forgotten to turn the machine on. This has been shown in studies as well with a number of different treatments. Everything from ultrasound, to acupuncture, to different forms of exercise therapies.
That's the placebo effect in brief, but that's not the focus today, our focus is on the nocebo effect.
So what is a nocebo?
Put simply, it is the opposite of a placebo.
It is the negative effect that a certain treatment may have on a person’s condition, sometimes in spite of whether or not it has any physical impact. It can happen when negative expectations result in negative outcomes, often despite any intervention being undertaken(3).
Still with me?
Research has demonstrated that the nocebo phenomenon is a neurobiological (the biology of the nervous system) process, one which can present itself through actual detectable changes in the body(2), and can even cause adverse health-related consequences(4).
In the clinic, and particularly in the world of pain, this is quite relevant.
This nocebo effect can relate to treatments given, investigations, explanations and even the language we use. The interaction between the clinician or therapist, and the patient, as well as the context surrounding this can have a big impact(3).
All of these create an expectation in you as the patient as to how effective a treatment is likely to be, or how positive your prognosis is likely to be. This can have a placebo effect like I mentioned, or it can cause a nocebo effect.
To put this in perspective, we go back to the encounter I mentioned earlier.
I was meeting this particular patient for the first time. They had generalised lower back pain which they had been experiencing for a few months. As result, they were sent for X-Ray to investigate whether there was any physical reason for this pain.
Most of what was found were general age-related changes, which we would expect to see in anyone who had used their spine over time. I would have seen these things as quite normal, and if I was discussing these results with them I would have indicated as much.
Oh, and the results also showed a little old diagnosis of Degenerative Disc Disease.
Now, anyone who read my article on damage (here) during Pain Week would likely know my thoughts on this diagnosis, if we can call it that.
Naturally, being told this made the patient quite concerned. You can’t blame them, it sounds serious.
The thing is, it’s not.
It’s actually quite a normal process which happens over time. Anyone over the age of 20 can have degenerative changes in the spine without any symptoms, and that obviously increases as time progresses. In fact, by the time you reach 60, almost 90% of people have degeneration of their spine(5), and that's just in people who have no symptoms. So you would actually be almost abnormal if you didn't (maybe I should say extraordinary rather than abnormal, because that sounds like it's a negative thing).
So we see a relatively normal scan, which should be a good thing. The problem was, it hadn't been explained as such, and since they had seen this diagnosis, they were actually more worried. There hadn't really been much discussion about what this actually meant (which as you can see from the paragraph above, could have been done in a couple of minutes).
Now they were a bit more fearful of what was going on with their back, and whether they would make it worse. I'm sure there were a number of things running through this persons mind.
Degeneration sounds bad doesn't it?
If I kept moving too much, it would get worse wouldn't it?
Would I then end up more debilitated? Can I do more damage by moving?
As a result, they moved less, trying to limit any worsening of their symptoms and prevent further 'damage'.
Then believe it or not, their pain became worse.
What had most likely happened, was that the fear and anxiety they now had, which had increased since the rather negative diagnosis from their scan, was actually contributing to their pain experience. Nothing had changed physically, but their understanding, belief and approach had changed.
And not for the better
This is what I would call a nocebo.
Nocebo-like effects can happen for many reasons. They can be seen after negative diagnoses, with a perceived increase in symptoms because of negative expectations about the course of the disease. Think about this for a moment; if you had come to see me (or anyone) for some non-specific lower back pain, and I told you that there might be an underlying disc bulge that is quite serious and you should be careful in case you make it worse, how would that make you feel?
Is that likely to make your pain better or worse?
Would you be inclined to physically do more or less, move more or less?
It might not have an effect immediately, but what if you then didn’t bend for the next 3-4 weeks from fear you might make it worse?
This something which does happen quite regularly. Now it is obviously dependant on a lot of factors, but what it can do is create negative expectations. This can lead to unhelpful management strategies and ultimately poor outcomes.
It might come from your doctor or therapist, it might come from a friend or family member. You might not be told anything, but you know of people who have had long-term problems from a similar thing, some who can't work anymore because of it.
Remember Joe from down the street? His pain started out just like this and he hasn't been able to work since!
That worry might sit in the back of your mind, but it may still have an impact.
Evidence has shown that these verbal suggestions can cause increased anticipatory anxiety, facilitating increased pain transmission(6). Think about descending inhibition (the brain and spinal cords ability to reduce or block pain production), which I wrote about here.
This also works the other way.
Heightened anxiety and anticipation can make the pain experience worse via increased activity in the brain and spinal cord(4). The more threatening the brain sees the issue, the more likely it is to increase pain.
If we want to look at an example of this, a study by Keltner et al (2006) looking at pain transmission using MRI showed how the brain reacted to temperature. They used visual cues with two different groups, one indicating high-intensity, one low. They then caused a noxious (unpleasant) stimulus to each group which was the same. They then looked at brain images of both groups.
What you can see in the top image is that those participants who expected a high temperature had more activity in areas of the brain in response to this expectation. They also reported feeling a higher temperature.
Those people who had low expectations, experienced a lower temperature, and showed less brain activity in response to the noxious stimulus.
Now there’s a big focus on the verbal cues provided to people when we talk about nocebo. The same as with placebo. Explanations create context, and context is important.
But what about nocebo with certain treatments?
Are we, as therapists or healthcare professionals, causing you more pain with some of our treatments, inadvertently stimulating the nocebo effect?
In some circumstances, yes.
Someone with an acutely irritated lower back will know it's quite easy to increase that irritation. If I as the therapist come in an do a lot of poking and prodding, there's is a chance I'll cause more irritation. You might feel a momentary improvement, but it is likely to be short-lived. Chances are I would simply be reinforcing the peripheral signals produced at the site.
What about getting someone to do too much too soon?
It's not likely we're causing any damage but it’s quite easy to reinforce a movement as painful and threatening. If the central nervous system associates a particular movement with harm, and therefore creates pain to prevent that movement, then it's doing so in the belief it is protecting you. If we simply ignore that and do it anyway, we might actually be conditioning that pain response, as the CNS will continue to see it as threatening.
It would be similar if I got you as the patient to stop doing anything which may cause pain. We reinforce the fear of that movement.
Combining those poor explanations with a certain treatment can have the same effect
If someone experiences an acute episode of lower back pain and believes that this is due to their hips or spine being ‘out of alignment’ (tip: it’s not), they might choose to have a manipulation or treatment to ‘put it back into place’. This might result in some short-term relief and over a couple of different treatments, the back pain might improve. This may be helped by the treatment, or it may have been settling down anyway.
But if that person now believes that whenever they have back pain they are out of alignment and it won’t improve until it’s put back into place, it creates a negative expectation for their pain. It might end up being a bit of a self-fulfilling prophecy, where they experience pain until they see someone.
The best approach, regardless of the treatment you choose, is education. If I decide that someone may benefit from some manual therapy, but it ends up irritating them, what I tell that person about why that happened is very important.
If it’s just because the area is a bit irritable and not ready for that, I need to say that to reduce any fear or anxiety about the pain having become worse. If there is an expectation of a certain treatment, maybe because it has worked in the past, but I don't offer that because it isn't going to be the best option, explaining to the patient why is going to be important(7).
As I mentioned before, if the interaction between the clinician and patient is negative, or there is no trust, then that can create a nocebo effect as well(7). If someone has had bad or unsatisfactory experiences in the past with a particular profession, any future interaction with that profession or treatment provided, regardless of whether it is that same person or not, can be affected.
So what does all that mean?
While this is relevant to you as the patient, it is even more relevant for us as the clinician or therapist. It is our role to give you as accurate information as we can and educate you on what that information means. It is our responsibility not to create a nocebo through our education and treatment. Most of the time, pain does not necessarily mean anything serious, and we need to convey that to you. If we do feel it is a serious issue, then we need to be open about that too, but not create any more worry or stress than is needed.
Misinformation in healthcare, and pain in particular, is quite common. A simple search on Google will tell you that. There isn't always a definitive answer for why you might be experiencing pain, and searching for a cause can sometimes cause more harm than good. We don't always have all the answers, but we need to be open and honest about that and discuss the best options available.
There are many different opinions out there, and there isn't always one right answer, but rubbish explanations and beliefs don’t help you.
What to remember:
The placebo and nocebo effect can be powerful contributors to outcomes;
It goes beyond just being positive or negative about the situation, it is influenced by your beliefs and expectations;
Unhelpful explanations and or experiences with treatments can impact on pain and health;
Good understanding and education about your specific situation is important;
If you are uncertain of a diagnosis, or an explanation for your pain, injury or illness, ask for more information. Discuss this with your health professional. They might not have all the answers, but they should be willing to talk about it.
Stewart-Williams, S, and Podd, J, 2004, The Placebo Effect: Dissolving the Expectancy Versus Conditioning Debate, Psychological Bulletin, Vol. 130, No. 2, 324–340;
Price, DD, Finniss, DG, and Benedetti, F, 2008, A Comprehensive Review of the Placebo Effect:Recent Advances and Current Thought, Annual Review Psychology, 59:565–90;
Colloca, L, and Miller, F, 2011, The nocebo effect and its relevance for clinical practice, Psychosom Med, 73(7): 598–603. doi:10.1097/PSY.0b013e3182294a50;
Enck, P, Benedetti, F, and Schedlowski, M, 2008, New insights into the placebo and nocebo responses, Neuron, 59(2):195–206;
Brinjikji et al, 2015, Systematic Literature Review of Imaging Features of Spinal Degeneration in Asymptomatic Populations, American Journal of Neuroradiology 36:811;
Benedetti, F, Lanotte, M, Lopiano, L, and Colloca, L, 2007, When words are painful: unraveling the mechanisms of the nocebo effect, Neuroscience, 147(2):260–271;
Tracey, I, 2010, Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans, Nature Medicine, vol. 16/11, 1277-1283.