Episode 23 – Pain (part 2); chronic pain

This weeks homework – TEDx – Why things hurt.

In the last episode we discussed that when it is functioning properly the pain system is a good thing, designed to keep us safe.

This understanding of what pain is, why we have it and how it is generated is important when it comes to understanding chronic pain. As a quick clarification the word “chronic” in a medical context refers to how long something has been going on for, it does not refer to the severity. A chronic pain is pain that has been going on for a long time. The opposite, acute, is something that has recently started.

We discussed that pain is a warning system, designed to alert us to perceived danger, and because of this, the intensity or severity of pain we experience is dependent on context. The brain will amplify or reduce the severity of pain depending on its perceived level of danger, and survival benefit of making us feel the pain. We explored the idea that sometimes if this system malfunctions pain can occur in the absence of a disease or injury in the tissues of the body, if the brain is perceiving danger in this area it will create pain. However, the presence or absence of injury does not make the pain any less real or legitimate, and it doesn’t mean that we are making the pain up or that the pain is “in the head”.

When we experience pain, it is always real, because pain itself is an experience. However, when we experience pain it does not necessarily mean that something dangerous is happening in our body tissues. It does, however, always mean that something is wrong. There is something wrong because we are in pain. If it is not something wrong in our bodies then it must be a fault with the warning system itself. My favourite analogy is with an emergency light in a car. If your “check oil” light comes on, and you check the oil and its fine there might be a problem with the light itself.

In chronic pain syndromes such as chronic regional pain syndrome or fibromyalgia, there is a fault with the pain system itself. It has got stuck on, or is stuck at full volume. The brain is generating pain even though it is not in our best interests to experience pain. The brain is perceiving danger in a particular area of the body even though that part of the body might be working OK. The pain itself, however, is 100% real. Just like with the warning light in the car. The light is still on, it is just as bright and distracting, even though the oil level might be OK. You are not imagining it, it is not an hallucination, and you are not making it up. It is just that the reason it is on is a problem with the light itself, not the engine.

Although all pain is real, there are different categories of pain. Because the production of pain by the brain is a complex process, when we experience pain the problem can be in different places, in the tissues, in the nerves themselves, or in neural networks in the brain.

Pain scientists describe three different types of pain based on the level in the pain system which is triggering the pain. There is nociceptive pain, where the pain is being triggered by activation of the “warning” pain neurones in the tissues, in a response to injury or damage to the tissues (the pain you experience when you trap your fingers in the door); Second is neuropathic pain, where the main trigger is not in the body tissues but within the signalling nerves themselves, the nerve itself has been damaged, infected or trapped, and is then sending excessive danger signals to the brain, even though there is no danger or damage in the tissues. This is the kind of pain you get from nerve damage such as in sciatica, diabetes or due to shingles. The third type of pain is central pain, where the pain system in the brain itself is producing pain regardless of damage in the tissues, or signals from the nerves. This is the kind of pain that is responsible for a lot of chronic pain and chronic pain syndromes, such as IBS, fibromyalgia, TMJ joint dysfunction and Chronic pelvic pain. Sometimes to simplify this the first two types of pain are described as “body pain”, whist the third is referred to as “brain pain”. It is important to understand that ultimately all pain is “brain pain” because the brain is always the final step in the pain pathway as it is responsible for creating the experience of pain. What this refers to is which level of the pain pathway is most responsible for the initiation of the pain. In general immediate pain is more likely to be the first type, whilst pain that has been going on for months or years, or pain that moves from one place in the body to another, tends to be the 3rd type; the central or “brain” pain.

Again, this can be difficult to understand. If I am saying this 3rd type of pain is produced by the brain in the absence of damaged tissues how is this different from saying the pain is all in the head? How is it not saying that the pain is imagined?

There are several ideas that come along with the “all in your head” concept, and they play a role in why chronic pain and other central sensitivity symptoms can be such emotive and controversial areas of medicine. I think it is best to address these head on. To name the beast. If this concept is misunderstood, it might imply several things that are simply not true. That the pain is “imaginary” and not real pain. That the pain is less legitimate. That its “just stress”. That people could choose not to be in pain. That people are weak or somehow deficient for experiencing the pain. That people are to blame, and the pain is somehow their own fault. That they are making the pain up for secondary gain, or that they are malingering. That this pain is less deserving of compassion, love, and medical attention. We make it into a moral issue, a hierarchy of pain, that “tissue” pain is somehow a superior, more noble type of illness than “central” or “Brain” pain.

All of these ideas are completely wrong and extremely harmful. But it is important to voice them. Because when we feel offended by something it is because a little part of us, deep down, suspects it might be true. We feel angry because we have activated our shame. It is important to confront these doubts so we can understand how wrong they are, not to convince other people, but to convince ourselves. So that we can be compassionate to ourselves and seek helpful solutions.

These ideas are incorrect on multiple levels. On a practical, societal, biological, pathophysiological, psychological, philosophical and spiritual level, this way of thinking about pain is unhelpful and wrong. We touched on this a little bit in episode 13 from a more general perspective concerning the nature of our bodies and our minds.

Fully understanding the magnitude of how wrong these ideas are involves some complex ideas that may challenge some of our basic beliefs about reality. These questions around the nature of matter and consciousness, human autonomy and free will, have been puzzling scientists and philosophers for thousands of years. It’s fascinating stuff, and maybe in the future we can do some episodes about it if people are interested.  For this episode though I think we can simplify things a little and just focus on the biology. Just this first level of explanation is convincing enough in its own right.

What I want to try to demonstrate is that from this “moral” perspective there is absolutely no difference conceptually between “brain” pain and “body” pain. Although they are produced by a different pathway, with the “fault” or “problem” being at a different level of the bodies pain producing system, they are equally “biological”, they are just as valid and just as real. The scientific explanation for this is the concept of neural networks. The processes that produce “brain pain” have biological systems that underlie the production of pain just as “body pain” does. The brain cells and synapses that make up your brain are physical things. They are no less physical than the knife, or the finger, or the pain receptors in that finger. Central pain is produced by a material, physical process. The same process, in fact, as all types of pain. It’s just that in chronic pain syndromes the warning system itself has a fault. Philosophically speaking an error or a problem in the central system is no different from an error or a problem in the tissues, such as infection or injury. People are not more or less to blame for, and no more or less in control of, one type of problem than the other. To suggest otherwise is like suggesting that a brain tumour is less real than other cancers, because it is “in the brain” and therefore somehow psychological or imaginary. 

In recent years there has been huge amounts of research carried out into pain, and our understanding of how the body and brain produces and maintains pain is increasing rapidly. The concept of neural networks is that pain is produced by sets of nerves in the brain connecting to each other in a circuit. When these groups or networks of neurones fire in a co-ordinated way pain is produced in a particular part of the body. When a particular combination or patten of neurones switch on, or light up, this will correspond to pain. These neuronal networks are involved in all our daily functioning. When we learn to ride a bike, play the guitar or catch a ball these activities are learnt through the creation of neuronal networks that correspond to these activities.

The theory is that when sets of neural networks fire together regularly the links between them are reinforced. The more times they fire in a coordinated way, the more likely they are to fire in this pattern in the future. This is how we learn automatic co-ordinated task, such as driving a car or a tennis swing. It is also how we may develop automatic, unconscious habits. Have you ever found a particular word or phrase annoying, but then a month later catch yourself using it all the time? “You know what I mean?”.

Neural networks for pain can be set up in the same way. For example, in chronic regional pain syndromes the pain often starts with an injury. Somebody breaks their ankle, and the brain produces pain in response to damage in the ankle. Over time the ankle heals, because in general the body is extremely good at healing itself, but the pain doesn’t go away. The theory is that the neural network that produces this pain gets “stuck on”. It continues to generate pain even though the initial injury has healed. Another way to conceptualise this is to think about amplification and volume. In chronic pain syndromes the brains pain system becomes supersensitised. It gets stuck on full volume, producing the maximum level of pain regardless of the type of stimulus it is receiving from the  body tissues. Again, I want to reiterate that this “excessively amplified” pain is just as real, and just as painful as any other type of pain. When someone breaks a leg it is exactly the same central systems that produce the pain. The pain itself is the same, but the level of the problem in the system is different.

Although the experience of the pain is just as intense the treatment for it will be different. Unfortunately, pain that is being generated due to a fault with neural networks and the central pain systems does not respond well to pain killers, because these act at a lower level in the pain pathway. They block messages that are being generated in damaged tissue or damage nerves from activating the central neural pain networks, but if the neural pain network is self-activating due to a fault within the central system itself they are unlikely be effective.

These three types of pain do not exist independently of each other. Even when there is damage to the tissues, such as a broken leg, the experience of pain is still dependent on the brains interpretation of levels of danger. Therefore, treatments that target central pain pathways may have an impact on all types of pain, since we know that the central system is the final common pathway of all pain types.

When I discuss this alternative understanding of pain with patients, after exploring the complex nature of pain production, and discussing that not all pain represents a problem with the body, that their xrays have demonstrated that the ankle fracture has healed well, and so the fact that they are still getting daily pain could indicate a central pain problem, rather than an ankle problem, the natural response is OK, so what do we do about the pain? This is a sensible response. If the problem is a neural network what can we do about it, and why does working out if the pain is a tissue, nerve, or central pain matter?

It matters because these different types of pain require different treatments. We know that immediate pain that is being triggered from the tissues, such as with traumatic injury, responds very well to opiate painkillers, like morphine. But nerve pain and central pain do not respond well. Have you ever wondered why the soldiers the movies with massive injuries get immediate relief from a little vial of morphine, whilst someone suffering with chronic pain might get limited response from large doses with no external signs of damage at all? For nerve pain we have painkillers that specifically act on nerve signals, such as gabapentin, which is an antiepileptic – it works by dampening down nerve signals. There is some evidence that this types of painkiller can also have some effect on central or “brain” pain, although to a lesser extent.

When it comes to treating central pain, things become a little more complex. Neural networks are far more complicated than the nociceptor or neural tract systems. The brain is processing information from a wide range of sources to calculate how much pain it is appropriate to generate. This includes signals coming from the pain nerves, but also other inputs, from our other senses, from our memory, and from our knowledge of the meaning of these inputs, and the brains predictions about the future. This system is so complex that it is beyond the current understanding of science and of western medicine. This means that we do not have medicines or surgical procedures that directly target neural networks to treat chronic pain. Chronic pain cannot be treated with a neurosurgical procedure to rewire neural networks because if we start digging around inside peoples brains it tends to make things a whole lot worse rather than better.

If we try to treat central pain using strategies aimed at the other pain types, this is often ineffective. It is therefore essential that we correctly identify pain caused by a central processing problem. Realising that pain is “brain pain” and not “body pain” is essential if we are going to effectively manage it. It is natural for people to focus a lot of energy on attempting to identify the physical underlying cause of pain, because we believe that once we find this out, we can do something about it. We can treat the problem and then the pain will go away. But if the cause is a central problem, no matter how hard we look, we will never find this physical solution, and by expending energy looking in the wrong place we may be inadvertently moving further away from recovery. If our only hope of recovering from the pain is identifying and rectifying a body problem, we are at risk of losing hope. If the problem is a central processing problem a body problem will never be found. By identifying different types of pain, we can shift the focus away from fruitless searches for the cause of pain towards treating the pain.

Although central pain is complex and does not respond well to western medical pharmaceutical or surgical procedures this does not mean that it cannot be treated. There is hope for those suffering from chronic pain, and this hope is provided by the concept of neuroplasticity. The idea behind neuroplasticity is that although neural networks are strengthened by recurrently firing together, these connections can be undone, and new connections formed. We can overwrite these patterns with new ones.

A good analogy is a tennis swing. If you taught yourself tennis you may have mastered an inexpert swing. If you subsequently get tennis lessons as an adult, you may need to learn to change your swing. Initially this will be hard to do, because your current stroke has become second nature, and trying to change your swing may result in deterioration in your play initially. But with practice you can retrain this pattern, and by putting in the work to do this, you may be able to improve your overall game in the future. In the same way by recognising the role that neural networks play in producing pain we can find techniques to rewire these neural networks and reduce pain.

Although the neural networks that underlie the pain are physical, the mechanism for rewiring them may not be. A tennis swing has an underlying physical brain state or neural network that corresponds to it, but we don’t improve our tennis through neurosurgery. We have natural tools for indirectly influencing the physical structures in our bodies and brains. We don’t always need science or medicine to make significant improvements to our health.

This brings us once again to this important recognition of the link between body and mind which is central to our understanding of health and wellbeing. There is a two-way causation. Physical states in our bodies and brains produce our experience of being in the world, our thoughts, sensations, experiences, and emotions. But equally our thoughts, sensations, experiences, and emotions impact the physical state of our bodies. This is obvious in our everyday experience of the world. Thinking about food can make our tummy rumble and feeling sad can make our breathing fast and irregular and cause water to leak out of our eyes. These are real physical changes. They are not imagined. They are not “in the head”. Our mental lives impact our physical state in countless unmeasurable ways, both directly, through the complex internal workings of the body and mind, and indirectly due to its influence on our behaviour. If we feel stressed and this causes us to smoke the stress may have affected our breathing both directly and indirectly.

In the same way our mental lives, our experience of being in the world, has both direct and indirect impact on the creation of the neural networks in our brains, including those that produce pain. Although the exact mechanisms that are responsible for this two-way causation are not fully understood, either scientifically or philosophically, there is little doubt that they exist. There are lots of examples of how emotive experiences contribute to pain production, both anecdotally in everyday life, but also from formal scientific research.

Perhaps the most widely researched of these is the concept of placebo, and its opposite, nocebo. Most people have heard of the placebo effect. The idea that if we believe that we are going to benefit from an intervention the belief itself can be of benefit, even if the intervention has no direct physical effect. Although placebo is by definition a dummy or sham intervention it is widely recognised that it is a significant one. It has real, physical, measurable effects. So much so that we must control for it when we test the efficacy of other treatments. It is so effective that it is often exceedingly difficult to come up with interventions that are better than it. Most people think of placebo in terms of dummy pills, but there have been studies demonstrating benefits for all sorts of different placebos. Interestingly dummy injections are more effective than dummy pills, and red dummy pills are good stimulants, while blue ones are better sedatives. People have shown benefit for sham meditation and even sham knee surgery. Patients were anesthetised, the knee was opened up, and then stitched closed again without doing the surgery. This was so effective, in fact, that it was found to be just as good as the real surgery. It is important to note that these are statistically significant changes. They are not imagined benefits. The placebo effect causes genuine changes in our bodies and minds and produces genuine improvement in our health. What is perhaps even more fascinating is that studies have shown significant benefits to placebo even when people are told that the treatment they are receiving is placebo. People often say that something is “just placebo” to mean “not significant”, but this is a misunderstanding, because the placebo effect is incredibly significant, and very real. This is widely accepted in the scientific community, to the point of being almost beyond doubt. It could be argued to be one of the most widely studied interventions ever, since a huge number of scientific studies contain a placebo arm.

We know that placebos do not exert their effect on health through direct physical interactions at a biochemical level. They have deliberately been designed to be inert. The natural conclusion is that they must be having a physical effect through a mental or psychological process. The belief that we are going to get better causes us to get better. There is also evidence that the opposite is true, the nocebo effect. If we believe that an intervention is not going to work, or that it is going to produce a negative symptom, then it will. This is thought to be responsible for many adverse reactions and negative side effects to prescribed medications. Now it is important to understand that these effects are not “just in the head”. They may start in the head, but because our bodies and minds are not separate this can translate into real, measurable changes in the physical state, the biochemical make up, of our bodies and brains.

What this means is that when it comes to pain, even though the pain is real, and has a definite biological, physical cause underpinning its production, we can influence this pain though non-physical interventions. Tablets and surgeries are not the only things that can help us to reduce pain. But the use of “non-medical” interventions in no way implies that the pain is “all in the head”. Non-medical interventions can have real medical consequences.

OK. We have come a long way, and I think its time for another break. I did warn you that this was the advanced class. For your homework this week I want you to watch a Ted talk by pain scientist Professor Mosseley (Not from HIMYM) which gives an excellent summary of some of the ideas we have discussed so far.

I understand that these last two episodes on pain have been rather theoretical, and you may be feeling that you are no closer to finding solutions. Its all very well learning about placebo, but what’s the use if we are still in pain. In the next episode, which will be the final one on pain, I am going to discuss how this new understanding can help us to start finding some practical solutions, and hopefully you will join me here next time.