Pain Concern

Half a century worth of research exists on neuropathic pain but what are the latest developments?

To listen to this programme, please click here.

This edition of Airing Pain is facilitated by the neuropathic pain special interest group (NeuPSIG) of the International Association for the Study of Pain (IASP).

With the previous edition of Airing Pain focusing on the ‘psycho’ and ‘social’ of the bio-psycho-social model, this programme tackles the ‘bio’ component.

In this second instalment in a mini-series on neuropathic pain, Paul Evans delves into the latest scientific developments on the condition and the ways in which the gap between research and treatments could be bridged.

Following on from Airing Pain 115, which concentrated on targeted Pain Management Programmes, this edition discusses the ‘bio’ element on dealing with neuropathic pain. Speaking to Professor Srinivasa Raja, Paul discusses what exactly is going on in the brain with neuropathic pain. Professor Raja provides a valuable explanation of the science behind the condition.

Patrick M. Dougherty, Professor at the Department of Pain Medicine at The University of Texas MD Anderson Cancer Centre then shares with Paul the latest advances in neuropathic pain research. He examines the link between cancer treatments and the condition as well as the potential for treatments such as immunotherapy to combat neuropathic pain in the future.

Issues covered in this programme include: Neuropathic pain, the bio-psychosocial model, allodynia, nerve injury, post-herpetic neuralgia, pain after shingles, pain after amputation, differences between men and women, chemotherapy-related pain, cancer, multidisciplinary pain teams, and personalised pain management therapies.

Paul Evans: This is Airing Pain, a programme brought to you by Pain Concern, the UK charity providing information and support for those of us living with pain, and for healthcare professionals. I’m Paul Evans, and this edition of Airing Pain has been supported by the International Association for the Study of Pain.

Patrick Dougherty: The idea that you could use immunotherapy for chronic neuropathic pain – that’s a completely new vista. This sort of research has only come up now over, like, the last three or four years. So this is a whole new vista.

Paul Evans: This is the second of two editions of Airing Pain about neuropathic pain, a condition caused by nerve disease or nerve damage. The biopsychosocial model for managing chronic pain recognises that the biological, psychological, and socio-environmental factors all feed into each other and affect the pain. And that’s why multi-discipline pain teams made up of psychologists, physiotherapists, occupational therapists, physicians and other disciplines can be so effective in helping people live with their pain.

In the previous edition, we looked at how the psychological and social elements of people’s neuropathic pain are addressed at the National Hospital for Neurology and Neurosurgery Pain Management Centre in London, and I recommend you listen to that. In this edition, I want to look at the biological component of the biopsychosocial trinity, and in particular, to the progress or otherwise, that’s been made into the understanding of neuropathic pain, and what developments and treatments might be just around the corner.

In May of this year, that’s 2019, the International Association for the Study of Pain brought together the world’s leading experts on neuropathic pain in London to share experience and knowledge. One of those is Professor Srinivasa Raja of Johns Hopkins School of Medicine, Baltimore, in the United States. He’s internationally recognised for his research into neuropathic pain.

Srinivasa Raja: One of the earlier things that we were seeing is that in patients who had nerve injuries, they had chronic pain, they would have pain long after their, quote-unquote, tissue injury healed. And they would come up with this sensation, where they would say, you know: ‘Just touching that area, or even rubbing of things bothered me.’ This phenomenon is called allodynia, or pain to sensations that are normally not painful. So we were wondering, you know, what could be causing this, you know, is it because of change in how the normal pain signalling nerves or pathways change? Or is it something else?

So we brought some of these patients, and a simple experiment we did was we applied a tourniquet around their arms. So, after the tourniquet, the sequence of loss of sensations in nerves of different sizes are variable. So the touch fibres are often lost first, and then the pain fibres. So as soon as these touch fibres were lost, you know, these patients lost the sensation of this hypersensitivity, which told us that what’s happened is, there were changes occurring at the level of the central nervous system, such that this touch sensation – which in the spinal cord at higher centres, has a common termination with where the pain fibres go – there were changes in the level of the spinal cord resulting in a phenomenon called central sensitisation. That is, it’s almost like the amplifier or the volume has been increased at the level of the central nervous system, such that now even kind of activating these fibres, which on normal individuals we would call as touch, now those individuals feel that as pain. So, this is one of the clinical aspects of understanding that injury to nerves changes how the central nervous system now perceives different sensations. And this also led to a lot of investigation by numerous investigators, looking specifically at the level of the spinal cord and even the brain, [at] what we now call the neuroplasticity [of the brain], or how these signalling mechanisms change. And now we know the molecular biology, we know a lot about it. And this has led also to possibly identifying targets for treating patients with this type of presentation.

Paul Evans: Let me go back a little bit to see if I understand this: a tourniquet on my arm, and I will lose touch sensation. Lots of us will have experienced that, [for example] when we say: ‘oh my foot has gone to sleep’. At what point do you stop the pain signal?

Srinivasa Raja: These patients, when they lost the sensation of touch, could still feel a pinprick, so their pain was still intact. But what they lost also was that hypersensitivity phenomenon where their touch resulted in the sensation of pain. And this is something we commonly see, particularly with patients with post-herpetic neuralgia or pain after shingles. You know, the common site for shingles is often the chest wall. And women are much more prone – two-to-one, almost – [to experience this] than men. And the common complaint that they’ll present to us is that [they] can’t wear a bra, you know, clothes are very uncomfortable. That rubbing of the clothes on that skin is very uncomfortable.

Paul Evans: Explain to me now – we’ve gone through the putting the tourniquet on and losing touch. What is going on in the brain with neuropathic pain?

Srinivasa Raja: This is a challenging question, because we’re talking about half the pain research community, working for almost half a century trying to understand this. The good news is that we have made enormous progress in understanding the science, the molecular biology, the neuro-physiology or the changes in the nervous system. The unfortunate sad news is, it hasn’t been translated into new treatments for patients with neuropathic pain. So there’s a big gap between the advances in research versus what we call translating that into new treatments for patients. A significant new area of research is to try to understand why this gap [exists] and what may be causing it. But to go back to answering your question, what we have understood is that changes occur at every level of the pain signalling pathway. In certain cases, this occurs at the level of the periphery at the site of injury itself. Again, I’ll come back to the amputation example, where a nerve is often cut at the time of the amputation. And these cut nerves form what’s called a neuroma, which is a nerve trying to grow back to its original site. And these neuromas are very sensitive, they are active, and they fire spontaneously, almost like seizure activity of a peripheral nerve. And these signals, [which are] constantly going from the periphery to the nervous system, are sending signals to the brain saying [that] there is a problem somewhere in the periphery. So the first thing – and this phenomena is called peripheral sensitisation, or changes in the peripheral nervous system. These, kind of, ongoing signals in turn cause changes at multiple levels in the central nervous system, at the level of the spinal cord, the level of the thalamus in the brain and the cortical levels, where this constant barrage of signals changes how the central nervous system perceives the signals. And it’s altered in a number of ways, which globally is called a central sensitisation. So this combination of peripheral and central sensitisation in various degrees can occur at different brain states.

Paul Evans: So with an amputation, those nerves [which are] firing off at the amputation, [are] looking for where they were, presumably, and [are] maybe overloading circuits in the brain?

Srinivasa Raja: You said that better than I explained. It is overloading the system in some ways, resulting in changes. Some of these changes seem to be more persistent than others. So, the struggle has been to see how we can revert this process, how we can reverse these changes occurring at the level of the central nervous system, and that’s been a significant area for research.

Paul Evans: That’s Professor Srinivasa Raja of Johns Hopkins School of Medicine in the United States. Professor Patrick Dougherty is professor of pain research at the MD Anderson Cancer Institute in Houston in the United States.

Patrick Dougherty: I’ve been interested in neuropathic pain, basically, ever since I was a postdoc or graduate student. And I was really very interested in how activation of the immune system impacts us in such a dramatic fashion. So imagine the last time you were really sick, how just godawful you felt, and that biology to me was extremely fascinating. Well, that carries straight over then into what happens to the nervous system following peripheral injury. And so, ultimately, that leads to what we know now is neuropathic pain. Any type of injury that either leads to some sort of a chronic maladaptive response in the nervous system, or direct injury to the nervous system that then leads to maladaptive responses, resulting in pain. Any of those would fit the category of what we call now neuropathic pain. And so, initially, our work was focused on trying to tie [in] specifically what we call psychophysics. Psychophysics means what people report when you apply energy to skin. And we want to model how human psychophysics is reflected in the activity of specific neurons within the central nervous system. And that was very successful, then led to an appointment at Johns Hopkins University, where I became interested there in changes in neurons in the brain related then to neuropathic pain.

That group of patients, now imagine the type of patient you’re looking at, they have neuropathic pain that has been inadequately treated to the point where they’re willing now to have a hole drilled in the top of their head, and put instrumentation inside their brain to try to treat this pain. This is how far down the road they’ve suffered, basically, and what they’re now willing to try. And [when] I’m looking at that I’m thinking, you know, these folks are so complicated, we’re never going to be able to figure out mechanisms in this condition. That then led me to think [about] neuropathic pain, [in which] we know the patient starts off basically normal, as far as pain goes, and then we cause neuropathic pain. And that’s those folks that are getting cancer treatments. Those people are basically neurologically fine. They had cancer, obviously, but they don’t have neuropathic pain. We know exactly what the insult is, it’s the cancer treatment. So the thought was, we could basically follow those people from before they get treatment, all the way to the end, [and then] we’ll be able to profile a whole natural history of neuropathic pain. Then we can start to come back to other folks that have neuropathic pain, we can stage them in and apply rational therapies. That was the idea.

Paul Evans: So you’re going down a known route, [which is] people with cancer, who’ve had treatment for their cancer. Some get neuropathic pain and some don’t. And you’re backtracking, then, for people who get neuropathic pain, and you don’t know where it started.

Patrick Dougherty: That’s basically the idea. It doesn’t really work out all that well. Because even cancer treatment-related neuropathic pain becomes very heterogeneous very quickly. In other words, there’s a lot of branch points in the road. And so again, to try to back up to anybody becomes complicated, but in any case, we can gain a lot of insights to the underlying mechanisms. And there’s been a particular advancement here lately, that is really exciting to us. And that is, we found that you have a group of neurons that innervate your skin, those are called primary efferent neurons. And those primary efferent neurons have cell bodies that basically are what give them sustenance, and metabolic support, and those are called dorsal root ganglion neurons. So the dorsal ganglion neurons are those that send their axons out to every tissue in your body.

What we discovered is that in basically every model of neuropathic pain now – and so this is where the road seems to converge – [in] every model of neuropathic pain that we’ve looked at so far, these dorsal root ganglion neurons become spontaneously active. They shouldn’t be spontaneously active, particularly if they’re a pain fibre. Pain fibres should be quiet, unless you’re having pain. To find out that if we give animals chemotherapy drugs, and we go in and deliberately injure nerves to try to produce a neuropathic condition, these dorsal root ganglion neurons become spontaneously active in animal models. Lo and behold, in the course of just simply talking to people at MD Anderson, it turns out that there’s a cohort of patients where their dorsal root ganglion neurons are going to be taken out in the course of trying to treat their cancer, so they get cancer into the spine, which is where near where the dorsal root ganglion lives, and sometimes to treat that cancer in the spine, those dorsal root ganglion neurons are taken out in order to get to the tumour.

What we found out is that if those ganglion neurons in human beings come from a part of the body where that patient is experiencing neuropathic pain, lo and behold, they are also spontaneously active. So now we can take animal models of the spontaneous activity, and we can directly line them up to the spontaneous activity that occurs in human neurons, and move back and forth, looking at those mechanisms that are shared or different between humans and the animals. This is really exciting, and a number of different labs now have confirmed that finding, and this is probably one of the biggest new movements in the field.

Paul Evans: Let me see if I can understand, ‘dorsal root ganglion’ – explain to me again what that is.

Patrick Dougherty: You may also hear it called, particularly in the UK, ‘posterior root ganglion’. The posterior root ganglion and the dorsal root ganglion are what are called the cell bodies; the centre of the neuron that leads to all of the peripheral endings that innervate your skin. So, when you move a hair on the back of your hand, there’s a neuron that’s back along your spinal cord that’s being activated by that. It has an axon that goes out and it wraps around the bottom of that hair cell, you move the hair, that causes that axon to discharge, that action potential goes back past the ganglion neuron and then into your spinal cord, [it] makes a synapse, [which is] a connection to another neuron. That then eventually sends that information to your brain and you realise: ‘Aha, a hair’s moving on the back of my hand, something’s happened!’ And then every sensation you can think of, for every part of your body, has a separate dorsal root ganglion neuron that has an ending in that part of the skin, muscle, bone, tendon, etc.

Paul Evans: So for cancer patients having treatment, that pathway was broken?

Patrick Dougherty: Not broken – let’s describe what happens to cancer patients when they get chemotherapy drugs. There’s a number of chemotherapy drugs, not every chemotherapy drug [results in neuropathic pain], but there’s many chemotherapy drugs. So for example, those used to treat breast cancer, prostate cancer, most every cancer of a solid tissue and some blood cancers, get sets of drugs that ultimately result in what’s called neuropathic pain. And what happens for all of these classes of drugs, and many people out there can attest to this. They probably will be nodding their head: ‘Yes, that’s me.’

You get these drugs, first, it leads to numbness in their hands, that progresses to tingling. That’s probably three quarters of patients [who] get those sensations as they get those drugs. And that’s fine. Again, mostly everybody’s going to get that, [and] mostly everybody that gets better. But [for] some of those patients, that numbness and tingling progresses to the point where their hands and feet feel like they’re on fire. Unfortunately, in about one-fifth of patients, that burning sensation, that numbness, that horrible pins and needles feeling, persists long after the cancer treatment’s over and now they would fall into the category of neuropathic pain patient.

Paul Evans: So you follow that track with certain patients having cancer treatment, and you try and replicate that.

Patrick Dougherty: Right, we can give animals chemotherapy drugs, though, we have to change our measurements a little bit, because obviously, the animals can’t tell us that they have ongoing pain, but there’s different behavioural measurements that we can put the animal in. So for example, folks that have gotten Taxol, often what they’ll tell you is that cold applied to their skin feels like it’s burning. So you can give animals Taxol, now put them in a little room, and you [make] part of the floor cold, and part of the floor [not cold], and what you’ll see is that the animal won’t go over to the cold floor, it’ll stay over on the warm floor. But since again, [with] the behaviour in the animal, you’re always kind of guessing what that means. I’m always really interested in what we can objectively measure. And that’s why I say when we find that you get this ectopic spontaneous activity of the neurons that otherwise should be quiet. And you can see the same thing in people. That’s what I like to zero in on, we don’t have to guess what it means: either that cell is discharging, it’s on, or it’s off. And then [with] people it’s either on or it’s off. And if we can figure out how to take the cells that are on and make them shut off, then the idea is that that’s what’s going to relieve their symptoms.

Paul Evans: Go on, then, can you?

Patrick Dougherty: We are making a lot of interesting progress. So the physiology gets to be really complicated really fast. But there are a number of potential therapeutic avenues that have been uncovered, that now we need to figure out how can we operationalize. There’s questions that have arisen that are very surprising. So there’s a paper we published a month ago or so, where what we did in that paper – we had these human neurons. In my lab, we did the physiology, and we determined which of these ganglion neurons that we had were in samples associated with pain and with the spontaneous activity. The human ganglion is big enough that we could divide it, and we can share part of that tissue with another laboratory in Dallas, headed by a fellow named Ted Price. Ted’s group broke those ganglion neurons apart and started looking at what we call their transcriptome. And the transcriptome is basically an output from their DNA. In other words, what part of the DNA were those cells activating, that we think would be related to the generation of the spontaneous activity. So we wanted to know, then what sorts of proteins are being made that either weren’t made before, or that used to be made that aren’t any longer being made. Again, the idea that we can reveal potential new therapeutic targets. And so, Ted did all this analysis. And what we did initially is we took all the ganglion neurons that we had from dermatomes, or segments of the body where patients had pain. And we compared the genetic information coming from all of the neurons from dermatomes without pain. And we run the analysis, and lo and behold, we got almost nothing, we couldn’t believe that – that couldn’t possibly be the right answer. Finally, we decided, you know, let’s just go ahead and we’ll pull all the women out, we’ll just separate men from women.

Then what we did was, we ran all of the neurons from men, segment pain; men segment no pain, and voila, we got a huge number of results. What that tells us is that men and women are actually changing different gene signals differentially with pain. So in other words, men are from Mars, and women are from Venus. In fact, we have quite distinct mechanisms by which our bodies, in this case, our neurons, respond to this insult – the toxic chemotherapy drug that then results in different ways of expressing pain. Now, what [does] that therapeutically mean? Well, that means that if you give a given drug to a man, that might work, [but] that same drug given to a woman may not. And then if you further follow the logic to that, even for a given man, there’s going to be variability within the male cohort. So even a drug that works in man number one may not work in man number two. It’s leading to the prospect that what we’re really going to need to do is come up with sets of what we call biomarkers, and these gene signals are a type of biomarker, there’s others. But we’re going to probably need to get sets of biomarkers for each person, and then thereby come up with specific therapeutics for each individual person.

Paul Evans: Wow, how or when will that impact on people with neuropathic pain?

Patrick Dougherty: That’s a hugely convoluted question, I think, you know. So number one, there are numbers of compounds that are out there that are available now. Most pain clinics have a set of drugs, and they try different sets for different patients. Some folks respond to one type of agent, others respond to another. So the pain clinics already understand that you have to tailor each pain therapy specifically to each patient. So that concept is already in place. What our research is showing is that we need a broader palette of therapeutics to address given folks, my lab is not alone in this approach. So there are a number of labs here in the UK that also are doing very similar work to us, in that they’ve got the same tissues, they’re also doing these same kinds of analyses. And one of the other things that we’ve discovered in these ganglion neurons that’s really important is that part of what causes these neurons to become active, is that when the ganglion becomes damaged, becomes inflamed, you get immune cells that go in there – and this is kind of funny, because it closes the loop on my whole career – that’s what it began with: how immune cells impact the brain.

It turns out that these ganglion become infiltrated by sets of immune cells, some are your angry uncle, and others are your soothing grandmother. And you can actually train the grandmother cells to go in and quiet everything down. And so with that idea being that you have immune cells that actually get into the ganglion that can either make things worse or better with one potential biomarker, and there’s other labs that are doing this, you could take a blood test, and from what’s in your blood – the immune cells that are in your blood – you may be able to get a picture of what potentially has gone into your ganglion that’s either driving that disease or that we can manipulate to try to make that disease go away. So the idea that you could use immunotherapy for chronic neuropathic pain, that’s a completely new vista that again, has been revealed by these new studies on ganglia and what’s going on in those ganglia.

So this sort of research has only come up now over like the last three or four years. So this is a whole new vista and what we simply need to do now is build up the sample sizes, I would say, you know, optimistically, as rapidly as biotech and the rest is advanced, let’s say five years, we can start actually having some real insights of what may be really good players to follow. And then it will be up to the pharma outfits and the new biotech outfits to operationalize those targets and come up with therapeutics. My side of the ledger is what’s called target identification. Once you get targets that are well validated, then you get into the legalistic part of bringing a drug to market. And so, I can’t tell you how long that might take based on which government you’re working with. If it’s in the US, it can be very slow, other countries move faster. So it’s hard to predict once you get into the actual regulatory process for each place, but I think as far as target identification goes, I would say within five years, we are going to have a very good idea of some promising new targets. I would say today, you know, our data says that a number of those that we could follow, but we need to validate the targets that we’ve identified. Other labs are identifying other targets, those should be mature enough, within five years, that you could start to operationalize those into therapeutics, and then you get into the therapeutic regulatory process, so that I can’t give you a handle on.

Paul Evans: That sounds very exciting, very positive. I guess it shouldn’t really come as a surprise that the same drug will work differently on different individuals. When we open our tablets, we see the list of the side effects, which could be diarrhoea, it could be constipation, it could be one of a hundred things, you know. Personalising designer drugs sounds really exciting.

Patrick Dougherty: Yeah, and it goes beyond just drugs, right? People need to be aware that pain, particularly a chronic pain condition, is not probably going to be treated by any magic-bullet drug. I mean, you’re going to need to go into whatever you can possibly do, that might work for you. Is that walking? Is it swimming? Is it yoga? Is it meditation? You know, there’s a whole number of different – both medical or drug – therapies and then non-medical therapies.

So MD Anderson, that is one of the pain treatment centres – what’s called a multidisciplinary pain centre – where basically whatever works for a given patient is what you’re going to try. And it’s probably not going to be one thing, there’s probably not one magic bullet. Number one, the patient has to decide they want to get better. It’s all about patient buy in: if you give up, the chances of being fixed are small. So you have to be focused, that you are going to get better, this is a disease you’re going to overcome. Then you find the combination of medications that work, the combination of exercise, the combination of nutrition, etc., that works for you to get you back, so that you’re in the game and you’re functional again.

Paul Evans: That’s Professor Patrick Dougherty, of MD Anderson Cancer Institute in Houston. And I was speaking to him and Professor Srinivasa Raja, at the International Association for the Study of Pain Neuropathic Pain Special Interest Group conference earlier this year, in London. I will just remind you that whilst we in Pain Concern believe the information and opinions on Airing Pain are accurate and sound, based on the best judgments available, you should always consult your health professional on any matter relating to your health and wellbeing. He or she is the only person who knows you and your circumstances and, therefore, the appropriate action to take on your behalf.

Well, in this edition of Airing Pain, we’ve been focusing on the ‘bio’: the biological elements of the biopsychosocial model for chronic pain. And please do listen to the previous edition of Airing Pain to learn more about these psychological and social elements.

Patrick Dougherty: They’re crucial. They’re absolutely crucial. If a person has chronic pain, and they become socially withdrawn, isolated, that quickly leads to depression, and an erosion of the spirit. And that person then is going to suffer even more. You have to get yourself back engaged into social environments, working as hard as you can to get yourself back to a normal level of activity. Meanwhile, we’ll be in the lab trying to come up with as many magic bullets as we can come up with. But I would be very surprised if we find anything that I say is the golden ticket, so to speak. It’s going to be a combination of things. Everyone’s going to have to sort out what specifically is going on with them in concert with their medical providers. What we’re hoping to do is come up with the tools and resources that, number one, we can [use to] better ascertain for that particular person what’s going on with them. And then, again, have the agents that can be then implemented.

Contributors:

Patrick M. Dougherty, Professor at the Department of Pain Medicine, Division of Anaesthesiology and Critical Care, The University of Texas MD Anderson Cancer Centre, Houston.
Professor Srinivasa Raja (John Hopkins School of Medicine, USA).

More information:

Neuropathic pain fact sheets and support, IASP https://www.iasp-pain.org/GlobalYear/NeuropathicPain
News, information and support at RELIEF, IASP Pain Research Forum https://relief.news/
The University of Texas MD Anderson Cancer Centre https://www.mdanderson.org/?_ga=2.205594646.486343381.1563359882-181156349.1563359882
Neuropathic Pain information, National Institute for Health and Care Excellence (NICE), https://www.nice.org.uk/search?q=Neuropathic+pain
Airing Pain 115: Neuropathic Pain 1 of 2: Targeted Pain Management Programmes.

Half a century worth of research exists on neuropathic pain but what are the latest developments?

This edition of Airing Pain is facilitated by the neuropathic pain special interest group (NeuPSIG) of the International Association for the Study of Pain (IASP).

With the previous edition of Airing Pain focusing on the ‘psycho’ and ‘social’ of the bio-psycho-social model, this programme tackles the ‘bio’ component.

Following on from Airing Pain 115, which concentrated on targeted Pain Management Programmes, this edition discusses the ‘bio’ element on dealing with neuropathic pain. Speaking to Professor Srinivasa Raja, Paul discusses what exactly is going on in the brain with neuropathic pain. Professor Raja provides a valuable explanation of the science behind the condition.

Contributors:

Patrick M. Dougherty, Professor at the Department of Pain Medicine, Division of Anaesthesiology and Critical Care, The University of Texas MD Anderson Cancer Centre, Houston.
Professor Srinivasa Raja (John Hopkins School of Medicine, USA).

More information:

Neuropathic pain fact sheets and support, IASP https://www.iasp-pain.org/GlobalYear/NeuropathicPain
News, information and support at RELIEF, IASP Pain Research Forum https://relief.news/
The University of Texas MD Anderson Cancer Centre https://www.mdanderson.org/?_ga=2.205594646.486343381.1563359882-181156349.1563359882
Neuropathic Pain information, National Institute for Health and Care Excellence (NICE), https://www.nice.org.uk/search?q=Neuropathic+pain
Airing Pain 115: Neuropathic Pain 1 of 2: Targeted Pain Management Programmes.

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Many people living with chronic pain are daunted by the prospect of long term or even permanent drug therapy. What are these drugs, are they safe and how do they work? Concerns such as these can stop people persevering with medicines that may offer a real, life-enhancing solution to their condition. Dr Mick Serpell explains how amitriptyline works and gives reassurance about the side effects that you might experience, especially in the early stages

The aims in managing chronic pain are obviously to relieve or to reduce the pain as much as possible, but this is not always achieved to the level patients would wish. Just as important then, is to improve overall quality of life by improving physical function, sleep, mood and psychological function. There are four main approaches to pain management:

1) physical therapy (physiotherapy, acupuncture, TENS (transcutaneous electrical nerve stimulation), etc.
2) drug therapy
3) regional analgesia (injection of drugs around nerves, joints or other tissues)
4) psychological therapies (techniques which improve coping with the pain).

Two types of pain

Doctors describe pain as either nociceptive (tissue damage), neuropathic (nerve damage), or a combination of the two. It is important to distinguish between the two types of pain, as they respond to different medicines. Nociceptive pain is the most common form of chronic pain, and examples include mechanical low back pain and degenerative or inflammatory joint pain. Although these pains may begin as purely nociceptive, over time there may be changes within the nervous system. Neuropathic pain often results from nerve damage that makes the nerve overactive. Therefore the drugs used for neuropathic pain are aimed at stabilisation or ‘calming’ of these nerves. Perhaps it should be no surprise, then, that drugs used in other conditions where nervous tissue is overactive or ‘excited’, such as epilepsy or depression, have turned out to be useful medicines for chronic pain.

Drug therapy

Conventional painkillers such as codeine and ibuprofen are used for nociceptive pain. They are often not effective for neuropathic pain. Most of the drugs used for the relief of neuropathic pain were originally developed to treat different conditions. For instance, amitriptyline is an antidepressant drug but is now used much more commonly for pain than for its original use. The situation is the same for some anticonvulsant drugs, such as gabapentin, which are used more frequently for neuropathic pain than epilepsy.

Change your lifestyle

Always remember that the medicine alone will not be enough. While drug therapy can play a role in the management of pain, changing your lifestyle (such as building up your fitness and getting more exercise), as well as learning to manage and cope with your pain better, are also vital to a successful outcome.

General principles of drug therapy

Your doctor will start you off at a low dose of your medicine and this is increased up to a suitable dosage and taken for sufficient duration until you obtain noticeable pain relief (or experience severe side effects). This procedure of increasing the dose step by step while monitoring the effect is called ‘titrating the dose’. If there is insufficient pain relief or troublesome side effects, the drug will be stopped. Your doctor is likely to gradually wean you off the medication over several weeks, in order to avoid potential sudden withdrawal effects. If you get partial, but inadequate pain relief, sometimes your doctor will add in another different drug, because ‘combination’ therapy can be more effective for pain than single drug therapy. However, there is an increased risk of side effects when more drugs are taken.

Once you are on the right dose and drug combination, then you may continue on the medication indefinitely. However, this should always be reviewed by you and your doctor, every three to six months. It may be that you decide the medications are no longer helping enough, or that you are now experiencing problematic side effects. In this case you should wean yourself off the medications gradually (one at a time) to ensure they are still benefitting you.

Most doctors agree that medication for chronic pain should be taken regularly ‘round the clock’ rather than ‘as required’ for breakthrough pain. It is easier to keep pain at bay rather than trying to chase it after it has been allowed to get out of control.

Antidepressants

The tricyclic antidepressants, such as amitriptyline, are the ‘gold standard’ for neuropathic pain as they are the most effective and best-known drugs for this condition. They can also be useful for chronic nociceptive pain, especially if there is a neuropathic component to it. They appear to work in the nervous system by reducing the nerve cell’s ability to re-absorb chemicals such as serotonin and noradrenaline. These chemicals are called neural transmitters. If they are not reabsorbed they accumulate outside the nerve cell and the result is suppression of pain messages in the spinal cord.

All in the mind?

The way antidepressants give pain relief is completely separate from the anti-depressant effect. The dose required for treating depression is much higher (150-250 milligrams (mg) a day) rather than the doses used for pain relief (25-75 mg/d). Amitriptyline also works in patients who are not depressed. Also, there are over twenty different antidepressant drugs available for treating depression, but only a small number can also be effective pain killers.

It is important that the patient is given a full explanation of the rationale for using antidepressant therapy. It is not the case that the doctor believes your pain is due to the depression. So do not think that you are not being taken seriously, or that the pain is ‘all in your mind’.
Depression can occur with chronic pain, it is usually ‘reactive’ or in response to the pain, suffering and loss of function, and often improves as the chronic pain improves. However, if severe, it may require simultaneous treatment with other antidepressant therapies such as psychology techniques or another antidepressant drug.

Starting amitriptyline

One in four people will get significant pain relief with amitriptyline. This is regarded as an excellent result for chronic pain conditions. It is started at a low dose (10 or 25 mg a day) and gradually increased in 10 or 25 mg increments each week up towards 75 mg if side effects are tolerable. Your doctor may advise you to go higher than this dose. The tablets are small and difficult to cut in half, and will often produce numbness of the tongue due to a local anaesthetic effect, but it is available as a syrup. It is better to use the syrup if small increases of dose are required during the titration (dose build-up) phase.

Keep taking it!

You may notice pain relief as quickly as two weeks after starting, but often amitriptyline requires to be taken for six to eight weeks at the optimal dose level before one can say the drug has been given a fair trial. Many people stop taking the medicine because they experience side effects early on but do not feel any benefit. However, if you can persevere, you will often get tolerant to most of the side effects after a few days to weeks and you may then start noticing the benefits of the medicine.

Although there are a number of side effects associated with amitriptyline most of them are extremely uncommon. The most common ones, experienced by only 5-15% of people, include dizziness, drowsiness, dry mouth, nausea and constipation. These side effects are generally harmless and, provided you do not exceed the dose, will not cause any damage. Most people find they adapt to these and eventually they go away. Amitriptyline is not addictive but if discontinued, it should be withdrawn slowly over several weeks in order to avoid withdrawal symptoms of headache and malaise. Your doctor can advise on this.

Not for everyone

Your doctor will not prescribe this drug for you if you have had an allergic reaction to amitriptyline or related drugs; a recent heart attack; or recent administration of drugs that can interact with amitriptyline.

When should I take it?

Amitriptyline is long acting, so only needs to be taken once a day. As one of the most common side effects is drowsiness, it is best to take it one to two hours before bedtime. This effect can be particularly useful if you suffer lack of sleep from your pain. Sometimes there is a ‘morning after’ type of hangover feeling, but this usually wears off with time. Occasionally amitriptyline can cause insomnia; if this happens it is better to take it in the morning.

Worth trying

If side effects are a problem, there are other similar drugs (for example, nortriptyline, imipramine, and now duloxetine) that are worth trying as they are nearly as effective, and often have less side effects,. Many of the patients I have seen have stayed on amitriptyline for years and say that it has transformed their lives. When dealing with pain, it is worth giving drug therapy a chance. Best results are achieved in combination with the non-drug therapies mentioned above. It is important to work with your doctor to try the different approaches so that you find the particular approach that is right for you. The optimal result is rarely complete pain relief. It is often that which brings you the best balance of pain relief, improved function, and minimal side effects, to give you the quality of life that you and your doctor both want.

Further Resources

Book onto a free Pain Education Session

Try a tool for making the most of your healthcare appointments

Get tips on making the most of your healthcare appointments

Mick Serpell is a Consultant in Anaesthesia & Pain Medicine for Greater Glasgow & Clyde NHS, and Senior Lecturer at Glasgow University.

If you would like to know more about the sources of evidence consulted for this publication please click here.

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Breast cancer is the most common cancer affecting women, and surgery – either to the breast and/or the underarm area – is the main treatment. There are two main types of breast operation: a mastectomy (removal of the whole breast) or a lumpectomy (removal of the cancerous lump) which is a breast-conserving surgery. The lymph nodes in the armpit can also be affected and it is common for women to also have a procedure for partial or complete removal of lymph nodes

How common is pain after surgery?

One of the first UK studies of chronic pain after mastectomy was conducted in Scotland in 1999. Over 400 women were surveyed at three years after their breast cancer surgery and 43 per cent still reported pain in the chest and upper arm. Many women reported problems with everyday activities, such as lifting bags, turning the steering wheel when driving and doing household tasks. For some women, the painful symptoms had started fairly soon after their operation; for others, symptoms had started later, possibly relating to radiotherapy and chemotherapy treatments.

Six years later, the same women reporting painful symptoms were resurveyed to find out whether they had recovered. About half of the women with pain at three years were, by then, pain-free; the other half still had pain (on average seven to nine years after their mastectomy). Of those still with pain, the women reported that they had ‘learned to live’ with their painful symptoms – many had tried alternative therapies.

The researchers then conducted another study across Scotland to understand more about the type of pain experienced both before and after breast cancer surgery. They assessed another 400 women before their breast cancer operation and very few reported chronic pain in the breast and upper body. After surgery, over half of the women reported moderate- to severe-intensity acute pain in the first week after surgery. Based on the ‘before’ findings, this pain was not a continuation of any existing pain. The researchers found that, of the 400 women surveyed, those who had more severe acute pain after surgery were more likely to have chronic pain at four and nine months after their operation. This suggests that if healthcare professionals could better control and treat pain immediately after the operation, they may reduce the proportion of women going on to suffer with chronic painful symptoms.

Nerve and phantom pains

Women with neuropathic pain (nerve pain) use terms such as ‘stabbing’, ‘burning’, ‘tingling’, ‘shooting pain’ or ’numbness’ to describe their symptoms. Surgeons may have to dissect branches of the main nerve running through the underarm when removing the tumour and surrounding tissue – this is unavoidable, but may be partly responsible for some symptoms.

Although neuropathic pain is the most common type of pain reported after breast cancer surgery, some women also experience phantom breast pain. Phantom pain is pain that seems to come from an amputated limb, breast or other body part. Phantom sensations after mastectomy might not involve pain, but there are reports of 17 per cent of women up to six years after surgery having phantom breast pain.

What are the risk factors?

Certain groups of women may be more at risk from chronic pain after their breast surgery than others.

Firstly, younger women do seem to be at greater risk of chronic pain than older women – this has been found after many different operations. This finding might be partly explained by the fact that younger people are often more active and are working, thus having persistent pain could have a greater impact on their daily life compared to older people who are perhaps less active. Or it may relate to nerve and tissue changes (how the body reacts to pain) as we get older.

There is recent evidence to show that women with other chronic pains are at greater risk of having chronic pain after their breast cancer surgery. This may include people who suffer from such conditions as chronic low back pain, irritable bowel syndrome, migraine, fibromyalgia and perhaps several other conditions as well. Changes in the nervous system may well lie behind many of these conditions. The field of pain genetics has also suggested that some people may be more susceptible to pain conditions than others.

It is entirely expected that women will be worried and fearful of their future when faced with a cancer diagnosis and impending surgery. Women who are very anxious and worried about their operation are at higher risk of both acute and chronic pain after surgery – so excessive worry and anxiety is a risk factor. This has been found with other operations, not just breast cancer surgery. It is important that support and information are offered to patients to help manage these feelings.

Preoperative preparation is vital; for example, a clear explanation about the operation and recovery process setting out the risks (and benefits) should be undertaken as standard practice.

Finally, one of the strongest and most consistent risk factors for chronic pain after surgery is the severity of acute pain in the days and weeks after an operation. Treatment and adequate control of acute pain immediately after surgery is very important and may ‘dampen’ the pain response, preventing longer term symptoms. Again, there is emerging evidence to suggest that women reporting pain with neuropathic characteristics (such as stabbing, tingling and numbness) in the early period after surgery may be at greater risk of having these symptoms persist in the longer term.

Treatment

Long-term pain after breast cancer surgery is treated in much the same way as other postsurgical pain. Some pain-relieving drugs may not be suitable if women are taking long-term hormone treatment. Refer to the leaflet ‘Chronic Pain after Surgery’ for more details.

Better understanding

An earlier version of ‘Chronic Pain after Surgery’ reported widespread misdiagnosis of pain after breast surgery. There are now many hundreds of articles from around the world reporting that painful symptoms after breast cancer surgery are common, disabling and can be challenging to treat. More is known about the types of surgery that may increase the risk of post-operative chronic pain e.g. surgery to remove all the lymph nodes under the arm (axilla).

Research studies now include larger numbers of patients than the early surveys. One of the largest studies ever conducted was undertaken in Denmark, where almost every breast cancer surgery patient in the country was followed-up two years after their operation. The research team found that out of over 3200 women, half still had pain in more than one area related to their operation, and 58 per cent reported sensory disturbances, such as numbness or sensitivity to touch. Overall 25 per cent of women had moderate to severe pain two years after their surgery. The study also revealed that many women suffering symptoms were under-treated and had poor pain relief and symptom control. This was a hugely important study and was published in the Journal of the American Medical Association (JAMA), one of the highest ranking medical journals. This publication has helped to increase recognition and raise awareness of the condition amongst doctors and healthcare professionals.

Professor Bruce is based at the Warwick Clinical Trials Unit, University of Warwick.

If you would like to know more about the sources of evidence consulted for this publication, please click here.

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What is chronic post-surgical pain? How common is it? How is it treated? Professor Julie Bruce & Professor Stephan Schug explain

What is chronic post-surgical pain?

Let’s start with some definitions – acute postoperative pain is the pain experienced immediately after an operation, usually lasting for days or sometimes weeks – this is entirely normal and expected. The surgical incision and surrounding area can be inflamed and tender – again this is fairly normal and is important for wound healing, where tissues and muscles repair themselves after injury.

Chronic pain is normally considered to be pain that persists or keeps coming back for more than three months or for longer than the expected healing time. Chronic pain that develops after an operation is often known as ‘chronic or persistent post-surgical pain’.

Knowing when pain becomes chronic after surgery is especially difficult because many people have had their surgery to treat a painful condition, such as a painful hernia or a long-standing back problem. Is the pain simply a continuation of the old pain, or is it new? And, even if it is new, is it related to the surgery?

Sometimes it is obvious that something has changed – nerve damage after an operation for hernia repair can be quite different from the discomfort felt before the operation. Another example is persistent tingling nerve pain in the chest wall after heart bypass surgery, which is very different from angina pain experienced before heart surgery.

Sometimes it is very difficult to tell the pains apart, especially if the original pain (that the operation was done to treat) was not in fact helped by the surgery. However, these are the features that can allow doctors to tell if you have chronic post-surgical pain:

The pain develops after a surgical operation
The pain lasts for at least three months after the operation
Your pain is not thought to be from other causes, such as an infection or cancer
Your pain is not the same as the pain from the original condition.

Surgical follow-up can be limited to one postoperative appointment, thus a follow-up clinic at approximately 8 weeks, to determine surgical ‘success’. Patients are then discharged and managed by the primary care team.

What type of pain is it?

The type of pain can depend on the operation itself, because the painful symptoms often relate to the distribution of nerves in the area of the operation. For example, after groin hernia repair surgery, people have reported pain down the front and inside of the thigh, or in the testicles. This may relate to potential irritation of nerves in the groin during surgical repair of the hernia.

We now understand more about nerve pain or ‘neuropathic pain’ which can arise from nerve injury. Typical characteristics and descriptions of neuropathic pain include stabbing, tingling, numbness, altered sensations and problems with sensitivity. It is not always possible to avoid nerve damage during an operation, especially during cancer surgery when removal of the tumour takes priority.

Treatment of chronic post-surgical pain

Treatment does not depend upon what sort of surgery you have had but rather on the mechanism that results in you having the persistent pain. For example, not everyone who suffers pain following a mastectomy will have the same ‘type’ of pain or for the same underlying reason. The treatment will depend on the characteristics of the pain and also the possible reason for the pain developing and not on the fact that the surgical operation happened to be a mastectomy.

It is important that the healthcare professional listens to your story, performs a thorough examination and allows you to give a full explanation of your symptoms. The healthcare professional then gains an understanding of the problem and the impact the pain has on your daily life. Patients often report finding this approach helpful in itself. Often they feel that, in the past, their symptoms have been dismissed and not taken seriously. Sometimes, people have been told that the pain will go away soon after the operation and this causes mistrust and resentment.

The best treatment for the pain will depend upon the mechanism causing it. Treatments include: tricyclic antidepressants, anticonvulsants, painkillers, TENS (transcutaneous electrical nerve stimulation) and injections. Based on our clinical experience, nerve destruction (peripheral nerve ablation) should not be used in the management of chronic post-surgical pain.

It is not always possible to control the pain and other symptoms adequately. In such cases, a psychology-based pain management approach or physiotherapy support can help you to cope with your symptoms and reduce the impact on your daily life.

How common is it?

A survey asked over 5,000 patients attending pain clinics across Scotland and the north of England carried out in the late 1990s about their reasons for attendance. Twenty per cent of patients thought that surgery was one of the causes of their pain and, of these patients, half thought it was the only cause. Until this report was published, chronic pain after surgery was thought to be rare. This is possibly because few patients were asked about persistent pain after their operation.

On average about 30 per cent of patients experience chronic pain after surgery, although this ranges from those with mild symptoms to those with more severe pain. Overall, only about five per cent of people report severe intensity pain, but five per cent is a significant number when you consider the huge number of operations conducted across the UK and globally.

Are there risk factors?

We are beginning to understand more about risk factors for chronic post-surgical pain. As well as the impact on quality of life for those affected, chronic pain is difficult and costly to treat, so understanding more about who is at risk of developing chronic pain after surgery is important as it may help in preventing the condition.

Certain groups of patients may be more at risk from pain after surgery than others. Women are more likely to experience chronic pain than men, although this is not always the case after surgery. Studies suggest women are more likely to report more severe acute postoperative pain, but the evidence for chronic pain is less certain.

Younger patients do seem to be at greater risk of chronic post-surgical pain than older patients – this has been found after many different operations. This finding might be explained by the fact that younger people are often more active and are working, thus having persistent pain could have a greater impact on their daily life compared to older people who are often less active. Or it may relate to nerve and tissue changes (how we react to pain) as we age.

People with other chronic pains are at greater risk of developing chronic pain after surgery. This may include patients who suffer from such conditions as chronic low back pain, Raynaud’s disease, irritable bowel syndrome, migraine, fibromyalgia and other conditions. Changes in the nervous system may well lie behind many of these conditions. There is growing research on the genetics of pain, suggesting that some patients may be more susceptible to pain conditions than others.

Patients who are more anxious and worried about their operation are at greater risk of acute and chronic postoperative pain – so excessive worry and anxiety is a risk factor. Preoperative preparation is vital; for example, a clear explanation about the operation and recovery process setting out the risks and benefits is an essential part of surgical treatment. Many hospitals run preoperative clinics whereby patients attend for tests in advance of their operation. This is an opportunity for careful explanation and discussion between the patient and health care team.

Finally, one of the strongest and most consistent risk factors for post-surgical pain is the severity of acute postoperative pain in the days and weeks after an operation. Treatment and adequate control of acute pain immediately after surgery is very important and may ‘dampen’ the pain response, preventing longer term symptoms.

More awareness needed

It is clear that chronic post-surgical pain is common, can be severe and may result in distress and disability for patients. Looking at the whole spectrum of chronic pain conditions after surgery, it is very unlikely that the cause of the pain is something that the surgeon has done wrong. It seems more likely that this is the inevitable result of surgery in a certain percentage of patients – approximately 30 per cent of patients experience chronic post-surgical pain of varying severity in the first year after an operation.

If it were more widely accepted that chronic pain can arise after surgery, some patients might decide against having operations that aren’t entirely necessary. Surgeons, who are undoubtedly trying to do the best for their patients, would also be reassured that pain is probably not the result of surgical error. Another benefit is that patients would have their pain acknowledged and would be treated more sympathetically.

Over the last 30 years, there has been a huge increase in medical research investigating the characteristics and potential causes of chronic pain after surgery – this has helped raise awareness amongst healthcare professionals and patients alike. There is still, however, much more work to be done to improve our ability to prevent people from developing chronic pain after surgery and to make sure everyone affected by this all too common condition receives swift diagnosis and treatment.

Finally, let’s look at some examples of different operations…

Pain after hernia surgery

Inguinal (groin) hernia is a common condition with an incidence of six per cent to 12 per cent in adult males. It affects men more often that women. The condition presents as a lump in the groin, due to a protrusion of intestine through a weakness in the abdominal wall in the groin. This lump can affect daily activities and is often, but not always, painful.

Surgery to repair inguinal hernia is one of the most commonly performed operations. Some surgeons use key-hole or laparoscopic surgery rather than an open incision. A mesh is often used to repair the abdominal wall weakness, secured in places either using stiches, penissleeve glue or staples. There is a small risk that the nerves in the groin can become irritated or inflamed by the implant or internal stiches.

Chronic pain after inguinal repair surgery is now a well-recognised condition – it is one of the most widely reported surgical conditions with hundreds of articles reporting prevalence of up to and around 30 per cent. Approximately 5 to 10 per cent of patients report pain after their hernia operation that interferes with daily living. There is now guidance recommending that it is safe for surgeons to ‘watch and wait’ with some patients who have a small pain-free lump, as long as the hernia doesn’t impact too much on their daily activities.

Pain after chest surgery

When you consider what is involved in surgically opening the chest (thoracotomy), it is not surprising that many patients suffer long-term pain afterwards. In order to gain access to the chest, the surgeon has to either remove part of a rib or spread the ribs apart. This inevitably causes damage to bone and nerves lying along the ribcage.

Experience suggests that many of the worst pain syndromes may be caused by partial nerve injury – thus it may be that a ‘clean’ cut of the nerve has a better long-term outcome, although this can result in numbness and loss of sensation. Although pain after chest surgery is fairly common, the severity of pain varies. In one study, 15 per cent of patients with chronic pain after chest surgery were sufficiently troubled to warrant referral to a pain clinic.

Pain after amputation

Pain after limb amputation is a well-recognised post-surgical pain condition. After limb amputation, the pain can be either stump pain or phantom pain (pain felt in the limb that is no longer there). In stump pain, patients often report a tender spot on the stump and this has led many surgeons to perform further operations to try and find the cause. Patients in the past have frequently had further amputations in the mistaken belief that this would cure the problem. Such operations rarely help stump pain and sometimes make it worse or make it more difficult for the patient to wear an artificial limb.

Phantom limb is a feeling or sensation that the limb is still there, this is normal and does not require treatment. But phantom limb pain (pain in the limb which is no longer there) can affect between 50 to 85 per cent of amputees. It usually starts in the first few weeks after surgery. Studies suggest that painful phantom symptoms can last between one hour and 15 hours a day and can vary between five days a month and 20 days. Pain severity can also be very variable.

It is now acknowledged that children get phantom limb pain and that people born without limbs also suffer from it. Recent research has shown that part of the pain after amputation arises due to activity in the brain itself and this underlines the futility of methods of treatment aimed directly at the stump.

Other chronic post-surgical pain syndromes

Other operations with known risks of chronic pain include vasectomy, joint replacement surgery, spinal surgery for back pain and breast surgery for cancer treatment. Other leaflets in this series discuss strategies for the management of chronic pain.

Professor Bruce is based at the Warwick Clinical Trials Unit, University of Warwick.

Professor Stephan Schug is based at the University of Western Australia, Perth, WA.

This leaflet is an update of a previous leaflet published by Dr Bill Macrae, now retired.

If you would like to know more about the sources of evidence consulted for this publication, please click here.

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We all know that what we eat can affect our health. New research, however, shows that there may be a specific link between diet and pain. Pain specialist Dr Rae Frances Bell tells us more, and outlines steps you can take to improve your diet as part of your pain management regime

It’s very important for people with chronic pain to maintain a healthy, balanced diet. There are several reasons for this. Firstly, the nervous system has the capacity to dampen pain. Most people have heard of the body’s own morphine-like substances called endorphins. In order to be able to function optimally, the nervous system requires specific nutrients such as essential amino acids. One example is tryptophan, which is a building block in the synthesis of the neurotransmitter serotonin which is very important in the body’s own pain-dampening systems. Foodstuffs such as nuts/seeds, fish, eggs, beans, oats, chicken and turkey contain high levels of tryptophan.

On the most basic level, the nervous system needs nutrients. Certain vitamin deficiencies can cause pain problems. For example, vitamin B12 deficiency can cause very unpleasant peripheral polyneuropathy, which is nerve pain in both feet and also sometimes in the hands. Vitamin D deficiency can cause musculoskeletal pain, as can vitamin C deficiency.

Omega-3 and Omega-6

The World Health Organisation published a report in 2003 which described how there has been a global shift in diet resulting from different factors such as industrialisation and market globalisation. Our diet has changed from being predominantly plant-based to more high-energy density and processed foods, including a substantial increase in the intake of saturated fats and sugars. One factor the report focused on was the balance between dietary intake of omega-6 fatty acids and omega-3 fatty acids. The ‘ideal’ ratio between these fatty acids is thought to be 1:1, while ratios under 5:1 have been associated with reduced risk for heart disease, cancer and auto-immune inflammatory conditions.

However, in the average American diet today, the intake of omega-6 is around 15 to 25 times the intake of omega-3. Foods containing relatively high levels of omega-3 are cold water oily fish such as mackerel, herring and salmon, fish oil, flax seed and flax seed oil; while omega-6 is plentiful in poultry, and in many vegetable oils, especially soybean oil. Soybean oil is used in the production of fast food and snacks and I think this widespread use has particularly contributed to high levels of omega-6 in our diet.

Omega-6 has been linked to inflammation, which is something we need to aid healing in our body. But an exaggerated inflammatory response creates its own problems. Omega-3 has anti-inflammatory effects. Research has found that increased dietary intake of omega-3 reduces joint pain, morning stiffness, number of painful joints and consumption of non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis. The balance between these fatty acids in our diet is thought to be important. So one thing for pain patients to pay attention to with regard to diet is to ensure they have a sufficient intake of omega-3 while avoiding excessive intake of omega-6.

A number of foods contain substances which have anti-inflammatory properties, just like non-steroidal anti-inflammatory drugs. For example, in virgin olive oil, there’s a compound called oleocanthal, which has been shown to have anti-inflammatory and pain relieving effects similar to ibuprofen. This is really interesting because non-steroidal anti-inflammatory drugs can have a lot of side effects. If we can achieve some anti-inflammatory and pain-relieving effects through eating healthily that would be ideal.

Antioxidants

Antioxidants have anti-inflammatory effects and are found in many foodstuffs. Resveratrol is an antioxidant which is formed in certain plants when they’re under attack by bacteria or insects. It’s found in the skin of red grapes, and in red wine and grape juice, and it has powerful anti-inflammatory and neuroprotective effects. Antioxidants called anthocyanins are found in the reddish-blue pigments in blueberry skins and cherries and in animal studies have been shown to reduce inflammatory pain.

Unfortunately there is a lot of hype in the media about antioxidants, with multiple advertisements telling us to buy antioxidant products. You actually don’t need a huge intake and the best way to get antioxidants is through your diet, not through pills.

I think most people know whether their diet is healthy or not. If we’re busy and just snacking instead of eating regular meals, it’s not good enough. We need to be getting vitamins; we need to be eating more fish, less red meat and lots of fresh vegetables, especially green leafy and brightly coloured vegetables. It’s the colour pigments which contain the antioxidants, so if you think of a colourful, Mediterranean kind of diet then you’re on the right track.

Foods to limit

Some foodstuffs can increase pain. Professor Guy Simonnet and colleagues in Bordeaux have done interesting scientific research on polyamines. Polyamines are important for cell growth and we obtain most of our polyamines through the diet. Polyamines upregulate activity in a receptor in the nervous system which is involved in amplifying pain and a polyamine deficient diet has been shown in a rat study to reduce pain hypersensitivity. Oranges and orange juice contain very high levels of polyamines. That doesn’t mean you should stop drinking orange juice, it just means you should probably think twice before drinking large quantities on a daily basis. Peanuts and potato crisps also contain high levels of polyamines.

Some pain-relieving medications contain caffeine because it interacts with analgesic drugs and can increase the effect of paracetamol and aspirin. But caffeine has other attributes that are actually harmful and regular moderate to high intake of coffee or other drinks containing caffeine can cause problems. Caffeine blocks the effects of the body’s own relaxatory neurotransmitter adenosine. Everyone knows that coffee can disturb sleep. If you have chronic pain and sleep poorly, you will feel more pain. If coffee is consumed on a regular basis, it can also increase the risk of developing a chronic daily headache.

High levels of caffeine are linked to osteoporosis, so if you drink more than four cups of coffee a day your risk of developing osteoporosis increases. This is also the case for other caffeinated beverages such as cola and “energy” drinks. In addition to flavouring, sugar or sugar replacement and water, cola contains phosphoric acid and caffeine. The taste might be nice, but there is nothing else positive about cola. A regular high intake of cola or “energy” beverages can cause sleep problems and increase the risk of osteoporosis in the same way as coffee due to the high caffeine levels.

What to eat

At our pain clinic we regularly ask our patients what they eat. We started doing this more than 20 years ago and quickly discovered that many of them had a poor or sub-optimal diet. There can be different reasons for this – some pain patients suffer depression and have reduced appetite, or they simply don’t feel up to preparing meals. Most are unaware that diet plays a role in pain and that it is especially important for chronic pain patients to have a healthy, balanced diet. By bearing in mind some of these simple principles you may find ways to make the food you eat an important part of your pain management plan:

Pain patients should include foods rich in omega-3 in their diet and be careful with regard to foods rich in omega-6. Swapping dietary vegetable oils high in Omega-6 fatty acids (such as soybean, safflower or sunflower oils) with oils high in Omega-3 fatty acids (such as rapeseed or flax oils) or monounsaturated oils such as olive oil will help optimise the Omega-6/Omega-3 fatty acid ratio, as will eating more fish and less red meat. Think about getting antioxidants through eating colourful meals with fresh vegetables, fruit and berries. Cut out all kinds of cola or “energy” beverages. Reduce your daily consumption of coffee. Don’t drink coffee (unless it is decaffeinated) after midday if you have sleep problems.
Eat regular meals with no more than 4 hours interval- For example, 3 main meals + two light snacks and don’t skip breakfast. Eating regularly is especially important for patients with chronic headache.
If you feel you need to lose weight, ask your GP for a consultation with a dietician. They will probably advise you to cut down on saturated fats, sugars, processed foods and snacks, and to eat more fresh vegetables and protein.
Get enough vitamins through your diet. Vitamin B12 or cobalamin is abundant in shellfish, fish, egg yolks, beef, lamb and cheese.
Nearly a thousand people over 65 took part in a study to see if there was any connection between the amount of vitamin D they had in their blood stream and their experience of back pain. There was no relationship in men, but women who had less than a third the levels of vitamin D considered healthy by most experts experienced significant back pain, suggesting that women may be more vulnerable to vitamin D deficiency-related pain. A recent systematic review found a high prevalence of Vitamin D deficiency in patients with low back pain. We get vitamin D from sunlight, so in the winter most of us need a supplement in the form of cod liver oil or vitamin D tablets. Margarine and milk products are often fortified with vitamin D.
Vitamin C is an antioxidant with anti-inflammatory effects. As mentioned above, Vitamin C deficiency can cause musculoskeletal pain. In addition, research seems to suggest that a deficiency of Vitamin C may be a significant factor in the pain experienced by people with post-herpetic neuralgia. If you have post-herpetic neuralgia, maintaining good levels of vitamin C in your diet could possibly help you with your pain. Vitamin C is found in fruit and vegetables such as strawberries, oranges, kiwi, broccoli, and red peppers.

For dietary advice specific to your needs we recommend you consult your GP, pain specialist or a qualified dietitian. For more information visit bda.uk.com/publications/index.html.

Dr Rae Frances Bell is Head of Multidisciplinary Clinic, Haukland University Hospital, Bergen, Norway.

Dr Bell also discussed this issue in Airing Pain 4: Diet, CBT and Mindfulness.

If you would like to know more about the sources of evidence consulted for this publication please click here.

Prefer a PDF?Download

Please note: This leaflet is the process of being updated. The revised version will be uploaded in due course.

Most of us will have painful feet from time to time, but it’s usually possible to take care of minor foot problems by making simple changes. Podiatrist and University Lecturer Gordon Hendry gives guidance on looking after your feet and explains when and how to get help for foot pain

Why do people get foot pain?

All kinds of reasons. Risk factors for foot pain include obesity, certain types of foot posture, getting older and sports injuries. People with diabetes can develop neuropathic pain in their feet, and people with vascular problems can develop cramps. The big one we can all do something about is poor footwear.

What should I look for when buying shoes?

High heels and narrow pointy toes are the obvious shoe design features that are hard on our feet, but there are other things besides worth bearing in mind. Our Shoe Shopping Tips can help you make a foot-friendly choice.

Is it better to rest my feet if I have long term pain?

While it’s tempting to rest sore feet, it’s important to keep active for wider health benefits. The strength, flexibility and coordination of your feet and ankles is like anything else – if you don’t use it, you’re going to lose it!

Getting active not only makes you fitter and stronger, but will help to improve proprioception – your sense of where your joints are positioned and how they’re moving. This joint position sense helps you move more efficiently. Poor proprioception has been linked to osteoarthritis which causes pain and mobility problems.

How can I be active when my feet hurt?

If your feet are sore, activity needs a bit more thought than just running on a treadmill. It’s important not to make rapid changes in activity levels to avoid risking injury. Speak to your GP, physiotherapist or podiatrist if you’re unsure.

Swimming and cycling are good, low impact activities. Wearing flip-flops can make walking to the poolside more comfortable. Shoes with a good, hard sole are best for cycling.
The controlled smooth movements practised in tai chi, Pilates and yoga can help to improve strength, coordination and proprioception.
Gradually building up the distance you can walk can be made easier with a fitness app or a pedometer.
There are simple foot-strengthening exercises you can do at home, some of them even while sitting down! You can find a foot pain exercise programme on the Arthritis Research website.
Simple calf raises and toe raises can improve ankle strength and endurance. Using an exercise band around the leg of a chair and moving the foot in inversion and eversion directions against resistance can also improve strength around the ankle. Toe exercises train the little muscles in the feet which help to keep your toes straight and strong.

When should I seek professional help?

If there’s an obvious issue you think might be causing your feet to hurt (such as walking a long way in ill-fitting shoes), try adjusting that yourself. A lot of foot pain can be, and is, successfully self-managed.

However, you should go to your GP for a referral or go direct to a podiatrist when:

Painful feet have prevented you from doing everyday activities on most days over a two to four-week period
Your foot pain is starting to affect your quality of life, restricting your ability to enjoy leisure activities, to work or to spend time doing things with your family
Everything you’ve tried has either not worked or made it worse.

If any of the above apply to you, it’s better to get help sooner rather than later. That way you’ll reduce the loss of fitness that comes with inactivity and make it less likely that your pain will affect your state of mind or social life.

What can a podiatrist do to help my foot pain?

A podiatrist will usually be able to diagnose the cause of your foot pain and offer a treatment plan. Podiatrists have specialist knowledge with managing pain related to musculoskeletal problems, where abnormal mechanics in the foot lead to tissue damage and pain.

If your foot pain is caused by nerve damage related to diabetes or problems with blood flow, you may be advised to see other healthcare professionals who can help you manage those underlying conditions.

Orthoses and more…

Orthoses are specially-designed insoles that reduce unwanted movement and change the way forces (such as the impact of your foot on the pavement) are distributed. For example, an orthotic for heel pain might be designed to increase the contact the rest of your foot has with the ground to reduce the stresses on your heel specifically.

Podiatrists can also recommend exercise programmes to enhance the stability and strength of your feet and legs and give guidance on general foot care.

Good foot hygiene includes:

washing and drying between your toes
wearing breathable socks (why not ask for a pair of merino or cashmere socks next time you’re stuck for a gift idea?) and thicker socks in winter
avoiding cheap and nasty flip flops
applying sun cream to feet on those rare sunny days
applying moisturiser to dry, hard skin.

Dr Gordon Hendry is Lecturer in Musculoskeletal Rehabilitation at Glasgow Caledonian University.

If you would like to know more about the sources of evidence consulted for this publication, please click here.

Further resources:

It is unfortunately not uncommon for people in pain to be told by others (family, colleagues or healthcare professionals) that their pain must be ‘all in the mind’. Amanda C de C Williams gives some tips on how you can respond

There is a way of thinking that says that if something cannot be explained medically or identified by medical tests then it must be ‘psychological’. The idea is either that the person ‘believes’ that they have pain, but doesn’t really, or that whatever pain they have arises entirely from mental processes and is not ‘real’. It is different from acknowledging that pain and emotional distress or psychological disorders may be related.

The fact that current medical knowledge cannot explain something does not mean that a mechanism for the pain will not eventually be discovered leading to effective treatments.

If you have been told that your pain is all in the mind, here are four assertive responses you could use:

‘Pain is a mind-body problem. The two can’t be separated.’

‘I’m distressed because of my pain and the problems it causes. Pain causes distress, not the other way round.’

‘I realise it is good news that the investigations [X-ray, scan, blood tests] show nothing serious. But I feel pain because that’s what my nervous system tells my brain and no investigation can show that.’ After all, plenty of acute pains accepted as ‘real’ wouldn’t show up on investigations like that, from headache to muscle cramp to renal colic.

‘If you had pain like this, and it affected your life like it affects mine, don’t you think you would be worried/distressed/depressed/frustrated?’

Amanda C de C Williams is a Reader in Clinical Health Psychology at University College London, and Consultant Clinical Psychologist at the Pain Management Centre of the National Hospital for Neurology & Neurosurgery, London.

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Persistent pain can impact on mood and on many areas of life such as work, exercise and socialising. This leaflet is designed to give advice to people who have found it more difficult or have had to give up sexual activity because of pain

It is often a difficult topic for people to communicate about and health care professionals may not always feel skilled and confident in addressing sexual difficulties. Those not in a relationship may lose confidence and assume that a romantic relationship is now out of the question. Existing relationships can suffer, particularly if maintaining intimacy is challenging. Studies show that individuals with chronic pain are more likely to experience difficulties with sex than those without pain, and to be anxious about sexual activity.

Myths about sex

Lots of ‘ideals’ or myths about sexual activity are constantly promoted by the media (newspapers, magazines, TV, films etc.). It is really difficult not to take these ideals on board and you may hold them as a standard which your sex lives should live up to. Sometimes having these ideas in your head can make maintaining an active sex life alongside chronic pain even more challenging than it would be anyway. Some commonly held myths are:

Sex should be spontaneous – you should never have to plan it or talk about what you like.
Sex should be adventurous and different every time.
Sex is only for young, beautiful and able people.
Everyone else is having sex frequently – at least three times a week.
If a partner isn’t sexually satisfied, they will look elsewhere for sex and intimacy.

It is easy to see how these ideas add to the pressure which you all feel, to have a ‘perfect’ sex life. If you are finding sex painful, then these myths of how sex ‘should’ be can lead you to feel that it is not even worth trying, as you are so far from this ‘ideal’.

Bad experiences with pain

Over time, unpleasant sensations before or during sex, or a flare-up of pain afterwards, may mean that, as with any other activity, you reduce how often you do it, or avoid it altogether. If you continue to be sexually active, this may be because of worry about your partner missing out, rather than because you are enjoying it. The social myths about sex mean that you may not talk to anyone else about this lack of sex, including your partner, and this can feel very isolating. Despite the fact that not all couples are sexually active and that these difficulties are very common in pain, you may feel that you are the only person who is struggling with this. Keeping quiet about it may mean that you don’t realise that in fact your experiences are very normal.

Building up gradually

When sex becomes painful, you tend to avoid it when you can, only approaching it when you feel that you ‘should’ or when your partner wants to be intimate. This leads to an ‘all-or-nothing’ pattern of sexual activity, for example having no sexual contact for a couple of months and then having penetrative sex followed by a severe flare-up of pain. This ‘all or nothing’ pattern doesn’t usually work well for someone with persistent pain. A more helpful approach is to have regular sexual contact, which doesn’t necessarily involve penetrative sex. As well as helping your body to get used to sexual activity in a way which does not trigger a flare-up, it reduces your anxiety and helps you to stay intimate with your partner rather than avoiding any physical contact. There is a well-established graded approach to building up sexual contact known as ‘Sensate Focus’ which works well in reducing your anxiety as well as minimising the risk of flare-ups. This ‘step-by-step’ approach involves taking your sexual relationship back to a level where you feel your pain is manageable, staying at this step for a while (for example, a few weeks), and then moving up to the next level.

Desensitisation

Many persistent pain conditions have elements of ‘hypersensitivity’. That means that sensations which should normally be pleasant and normal, such as touch and stretch, can feel painful. We now have studies explaining that this can be because of changes in your nervous system and not necessarily because you are causing any harm. The good news is that the nervous system is capable of changing the response and the technique used is called ‘desensitisation’. For this technique to be effective, it is important to feel reassured that some temporary increases in pain do not mean that it is harmful. It is possible for a lot of people to gradually build up their tolerance by exploring self-touch regularly. The desensitisation process can be compared to going to a pebbled beach and being in pain the first time you run across the beach but gradually, as you do it more frequently, the soles of your feet get used to it – they ‘desensitise’. Once confidence grows in self-touch, a partner can be involved as long as there is clear communication about what, how long and where touch, stretch and intimacy can be tolerated. For this purpose, Sensate Focus techniques can be useful as a step-by-step approach to introducing intimacy without the pressure of achieving full penetrative intercourse.

Medication side-effects

Medications for pain are sometimes associated with unwanted side effects that can affect sexual desire and performance. You can discuss this with your GP or pain specialist if this is a concern. Sometimes people use medication to manage temporary increases in their usual persistent pain, often known as ‘breakthrough’ medication. It can be useful to take breakthrough medication prior to sexual activity if a flare-up of pain is likely afterwards, though you must take it as prescribed. Developing non-medical strategies for these flare-ups can be very helpful.

Communication

As with any activity involving someone else, you need to communicate to get what works best for you both. This can feel difficult whether you are in an established relationship or with a new partner. It can feel particularly difficult if you ‘buy into’ the myth that sex should always be spontaneous and so never needs to be discussed. To help with communicating about sex, you may want to rehearse what you are going to say, and in the case of a new partner, when you are going to say it. Emphasising how much you want to be close to them, and that you want to avoid your pain getting in the way, will reassure your partner that you are not using your pain as an ‘excuse’ to avoid sex. If it feels difficult to talk, you could consider showing your partner this leaflet to read, as a starting point for a conversation. It is difficult to communicate about what you would like without knowing it yourself, so you may want to start the desensitisation or sensate focus steps described above on your own, so that you know what you can do without triggering a severe flare-up of pain. You can then involve your partner at a later stage.

Prioritising sex

Like any activity which you want to do regularly, you need to prioritise sexual activity so that it becomes a normal and an enjoyable part of your life. It is very easy for it to get ‘lost’ in all the other pressures of day-to-day life, whether you have persistent pain or not. You also need to prioritise the elements of your romantic relationship which will help you to stay close, such as being affectionate and spending time together. Sometimes these elements can suffer when sex is difficult, as there is a worry that any physical affection will lead to sex, which will be painful. Communicating about this so that you can continue to be affectionate often makes a big difference to how close you feel to a partner.

Before sex

Remember that pain can be ‘wound up’ by several factors including activity, mood, environment and biological changes. Some of these factors may be possible to change and some not. Self-management approaches can be helpful here. There may be strategies you can use to manage the pain prior to intimacy, particularly those that help you feel relaxed. You may wish to involve your partner in these strategies such as having a bath or shower together, having a massage or listening to relaxing music.

Managing flare-ups

Flare-ups of pain are a normal part of living with persistent pain, and if they happen after sex it is best to have a plan for how to manage them, as this reduces your anxiety about them. Ideally you also communicate this to your partner so that they understand what you are doing. A flare-up plan for pain may involve, for example, having a hot bath, taking pain medication, using an ice pack, doing some stretches, and reminding yourself that the flare-up will pass.

Self-help resources:

Relate: relate.org.uk – for online resources and couples counselling, including counselling around sexual relationship difficulties
Overcoming Sexual Problems – Vicki Ford, 2010 – self-help book on cognitive-behavioural therapy for sexual difficulties (not just pain-related), including details on the sensate focus approach.

Sarah Edwards (Clinical Psychologist), Katrine Petersen (Physiotherapist in Pain Management), Katie Herron (Clinical Psychologist) are part of the multidisciplinary team at the Pain Management Centre at University College London Hospital.

They deliver self-management support to people with abdomino-pelvic pain (APP) via group programmes and individual sessions. Their work frequently involves supporting people with persistent pain with improving sexual activity and managing relationships, using approaches drawn from established pain management research and sex therapies. Following several years of experience, the authors have presented and published their clinical work internationally to encourage clinicians to facilitate open discussions and offer therapeutic interventions on sexual activity in the context of persistent pain to their patients.

If you would like to know more about the sources of evidence consulted for this publication please click here.

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People living with long-term pain may be offered treatment with a TENS machine to help ease their symptoms, but what is it? How does it work? And what can it bring to your pain management toolkit? Physiotherapist Dr Pete Gladwell draws upon his clinical experience and research to answer these questions and explain the effects and benefits of TENS

How does TENS work?

TENS stands for transcutaneous electrical nerve stimulation. TENS devices have been around since the 1960s and help in pain management by delivering electrical impulses across the skin.

TENS machines are usually a small box with wires leading to self-adhesive pads, although wearable belts suitable for back pain are also available. The pads are placed on either side of, on top of or close to the painful area. When switched on you get a tingling sensation under the pads. My usual advice is to aim for a strong, but comfortable, sensation. The right sensation for you can be found using the controls on the TENS machine.

The TENS machine works through different mechanisms. Some research shows that the TENS machine operates through the pain-gate, a special system that helps to block pain messages going up through the spinal cord. Other evidence suggest that the TENS machine also stimulates some of the opioid systems, or natural pain-killing systems, within the body. The third mechanism, which my research suggests as well, is the distraction mechanism; it may actually just take your mind off the pain.

Can TENS be useful to everyone?

For some people, using a TENS machine leads to pain relief. For others, the sensation just takes their mind off the pain for a while.

Unfortunately, for some people it is not helpful or they find the sensation too unpleasant. In our clinics we encourage people to change the sensation to suit them, but it may not work as people’s experience of pain is diverse.

People should NOT use TENS if they have epilepsy, a heart rhythm disorder, a pacemaker fitted or if they are pregnant (except for pain relief during labour). If you are unsure, speak to your healthcare professional.

As far as we can tell, the TENS machine can be used for all pain conditions, providing there is no health reason preventing its use. However, it can be difficult if you have many pain sites especially if the pain can move and vary throughout the day, so you end up chasing after the pain with the TENS machine.

People with widespread pain such as fibromyalgia syndrome may feel that it is difficult to choose a specific area to treat, but it may be possible to select one treatment area such as the lower back, to see if the TENS machine can offer an overall benefit. There is a randomized controlled trial exploring exactly this approach which is due to report its findings soon. However, people with widespread pain often have a localised pain problem which can be helped through using a TENS machine, even if it doesn’t help their more widespread pain. It is down to each individual to try out different approaches to see what may help them.

Different Strategies

We asked people who had experience of using TENS about the ways that they used their TENS machine, the benefits they got and how they overcame their problems. From this research, there seemed to be five main strategies that people had worked out to gain the most from their TENS machine:

Use the TENS machine only on a bad day or during a flare-up to help cope and get through the pain
Use TENS intermittently during the day during a rest break, perhaps in combination with relaxation techniques
Use TENS for particular activities (such as walking or sitting, e.g. in the cinema) which would otherwise have been difficult because of pain
Use TENS on and off all day to help with most daily activities
Use TENS in the morning, to help with the extra pain and stiffness that some people experience first thing.

These different methods show how a range of people can find using a TENS machine beneficial by using different strategies.

When it comes to the benefits, some people talk about direct pain relief. However, some people also find the distraction from their pain really quite helpful. This is known as counter-stimulation, where a more pleasant sensation helps you to manage your pain. These people asserted that the distraction was a separate benefit from pain relief, as it can just provide a break. Some people said that using TENS could help them to do more despite not necessarily reducing the amount of pain. Others found that TENS use could help them to fall asleep more easily. These aspects are currently the focus of research on the benefits of TENS machines.

Hints and Tips

One strategy some people find helpful is to use the machine when at rest in a comfortable position, perhaps while you are having a break or before sleep. Another strategy is to use TENS during particular activities that would otherwise be difficult to manage
The preferred type of sensation is personal. There are some people who feel that the stronger the sensation, the more effective the TENS machine will be. The settings on most machines can be adjusted to suit individual preferences and can be tweaked during a treatment session
Despite being hypoallergenic, the pads can aggravate the skin. Rubber pads with gel are an alternative that can be less of an irritant. However, some people do continue to react to the pads. In this case it is important to limit use to short periods where pain relief is crucial and also to change the position of the pads regularly to avoid the problem
Be persistent! Sometimes patients have to plug away at a problem for two or three months before they feel sure that they are getting the benefits. Changing the settings and changing tack can help you work out whether TENS can work for you.

More information

An information sheet can be found on the North Bristol NHS Trust Pain Clinic website here
Listen to Airing Pain 9: Relieving Pain, TENS and Acupuncture.

Dr Pete Gladwell is Clinical Specialist Physiotherapist in the pain management service at North Bristol NHS Trust in Bristol.

If you would like to know more about the sources of evidence consulted for this publication please click here.

Exploring neuropathic pain and the various ways it can be managed

To listen to this programme, please click here.

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In this edition of Airing Pain, Paul Evans investigates the ideas behind Pain Management Programmes, and highlights the importance of the patient in shaping their own treatment.

Internationally recognised Professor Srinivasa Raja speaks to Paul about the differences between nociceptive and neuropathic pain, as well as the complexities of chronic pain and its management.

Consultant Clinical Psychologist, Dr Clare Daniel examines the psychological and social components of chronic pain. She discusses the important role of the cognitive behavioural model in Pain Management Programmes.

Paul speaks to lead physiotherapist Diarmuid Denneny about the importance of the patient in determining the appropriate response to their pain, by taking into account their life and personal aspirations.

Finally, Cameron Rashide, a patient with neuropathic pain among other conditions, speaks of the pain management technique ‘pacing’ and how she has learnt to manage her pain through pushing herself ever so slightly outside her comfort zone.

Issues covered in this programme include: After a stroke, post-herpetic neuralgia, shingles, post-surgical pain, brain signals, emotions, exercise, loss of sensation, mindfulness, nervous system, neuropathic pain, nociceptive pain, numbness, pacing, psychology, tissue injury and trigeminal neuralgia.

Paul Evans: This is Airing Pain, a programme brought to you by Pain Concern, the UK charity providing information and support for those of us living with pain, and for healthcare professionals. I’m Paul Evans.

Clare Daniel: A good pain management programme is about responding to what the people bring. So when I was really interested in setting up a programme for people with neuropathic pain, people said to me, ‘Why are you doing this on diagnosis?’

Diarmuid Denneny: It’s well known that people with neuropathic pain wouldn’t tend to do as well on our general pain management programmes. Their outcomes from all the different measures weren’t as good, or as expected.

Daniels: I wanted to do it because of the differences I observed tailoring our intervention to what they were coming with.

Evans: Neuropathic pain is caused by nerve damage or nerve disease. It’s often described by those who have it as burning, aching, or like an electric shock. Many experience pins and needles, numbness and weakness. For some, it’s a stabbing pain in the middle of the night. For others, it’s a burning feeling felt throughout the day. Amongst other causes, it can be caused by shingles, diabetes, surgery or a stroke.

In May of this year, that’s 2019, the International Association for the Study of Pain brought together the world’s leading experts on neuropathic pain in London to share experience and knowledge. One of those is Professor Srinivasa Raja of Johns Hopkins School of Medicine in Baltimore in the United States. He’s internationally recognised for his research into neuropathic pain.

Srinivasa Raja: The International Association for the Study of Pain defines it as pain that results from a disease or injury that affects the somatosensory system. And that big term ‘somatosensory’ actually just means anywhere in the pain signalling process, from the periphery, which could be at the level of the skin, to the brain. The injury or the disease can affect anywhere in that process. Some good examples would be pain that persists after shingles, or herpes zoster, what we call a post-herpetic neuralgia; or a condition after a spinal cord injury; or after a stroke. So here we see that, like in herpes zoster, it’s initially a skin legion that affects the peripheral nervous system. In spinal cord injury it’s the spinal cord, but in stroke it’s the brain. So all of these, or injuries anywhere along this nervous system can lead to neuropathic pain.

Evans: The other term I’ve heard is nociceptive pain, how does it differ from that?

Raja: Nociceptive pain is that pain that could result from an actual or potential injury to tissues. Could be as simple as a pinprick, it could be a burn, or after a surgery, the immediate pain after surgery. So this is usually associated with a tissue injury mechanism.

In contrast, neuropathic pain specifically involves an injury to the nervous system. So, the main difference is what initiates and what causes the pain. But the patients also describe the pain differently, often. The neuropathic pain, there could be an area where the patient says, ‘I’m numb’, but immediately adjacent to it, even touching that area causes pain. So, this kind of challenging situation, where there is loss of sensation as well as amplified, or increased, sensation that coexists is typical for neuropathic pain.

Evans: So if I bang my finger, hurt my finger, that hurts, that sends messages up to my brain that he’s just banged his finger and the brain will translate that into pain. But that pain will go. It will heal. [Yes]. Neuropathic pain stays?

Raja: Not all neuropathic pain stays chronic. There may be some situations which we now call acute neuropathic pain, where the pain may gradually disappear with time. A good example of that may be the phantom pain that usually occurs after an amputation. Most patients, immediately after the surgery, or after the injury, will experience that sensation of pain in the missing part of the limb. However, the majority of those patients seem to resolve in time, it’s only a smaller subset of those patients who persist, and go on to chronic pain.

So the good thing about it is it seems that the body has some protective functions, and in most cases, fortunately for us, the pain resolves with time. It could be weeks to months. But in some cases these pain states persist, and it is this chronic pain state that becomes problematic to most patients.

Evans: So how do you deal with that?

Raja: One of the first aspects of dealing with patients with chronic pain is an appropriate assessment of their problem. An assessment includes not only the description of the pain experience, how they perceive it, but also functionally how this pain affects their quality of life, their day-to-day functioning. In most cases also examining the psychosocial comorbidities, one of the most interesting things is that the pain experience is different from individual to individual given the same injury, and therefore one has to assess what are the other environmental psychosocial factors that may also contribute to this chronic pain experience.

Evans: They call that the biopsychosocial model for pain, where everything around us, our bodies, our society, things that happen in the street and at home, everything feeds in to the pain.

Raja: A few decades back, neuroscientists, people trying to understand the pain mechanisms, thought that this was purely a biological mechanism. That there was injury to tissues, there were certain nerves that were excited, which resulted in the sensation of pain. What we have learned over the last several decades is that it’s much more complex, and that the experience of pain is modified, or modulated, as we call it, by a number of factors. It could be genes, it could be psychological environment, social environment, their prior experiences, and so it’s much more complex that a sensation or just trafficking or signals that go along pain pathways.

Evans: That’s Professor Srinivasa Raja of Johns Hopkins School of Medicine in the United States. We’ll be talking in greater detail about his, and others’, research about neuropathic pain in a future edition of Airing Pain. But in this edition I want to concentrate on those psychological and social components of chronic pain.

Doctor Clare Daniel is a Consultant Clinical Psychologist. Now leading psychological services at Buckinghamshire Healthcare NHS Trust, she previously worked at the National Hospital for Neurology and Neurosurgery Pain Management Centre in London.

Daniel: Psychologists tend to work with the cognitive behavioural model on different variations, and actually, the physiotherapists do as well, if they’re working in pain services. So the cognitive behavioural model, if you just picture a cross, on the four ends of the cross there are four words. One is thoughts, one is emotions, one is behaviour and the other is body. Ok, so thoughts, emotions, behaviour and body, and the idea is that they are all influencing each other. If a person’s fearful, their emotion is fear and they have chronic pain, the chances are that fear is going to turn up the volume, or the intensity of that pain. So that person needs to have input from a body practitioner, which might be a physiotherapist, but obviously thinking psychologically, but also a psychologist. Because you need to address the thoughts and the emotions, which is the psychology part of it, and the behaviour and the body, which is the physio part of it. But in an integrated way, because if you go to a non-pain service you’ll often get the psychologist that will just focus on thoughts and emotions and the physios that just focus on body and behaviour.

Evans: So it’s thoughts, emotion, behaviour and body.

Daniel: It’s just getting people to think about the likelihood of the influence, because actually, one cognitive behavioural model, which is acceptance and commitment therapy, is really trying to separate thoughts and emotions from behaviour. So regardless of what you’re feeling in terms of emotions about your pain, so ‘I’m really frightened about my pain, I can’t do something’, the intervention is to try and keep going with the behaviour, because it fits in with your values.

It’s about thinking about the interaction between the four, and in some respects can you just loosen that interaction. A classic example with neuropathic pain is even if people just experience the sudden electric shock type pain, trigeminal neuralgia (TN) is a classic example, they can be pain free for a long time, but their pain is still massively impacting on them during pain free times. A lot of the time it’s because of the thought, ‘well if I go outside, and if I get a sudden shock of TN, I might be stranded, no-one’s going to help me, I can’t get home, I might not have my tablets’. So it’s that fear and that prediction that make them stay, understandably, at home.

Evans: I would think that’s a perfectly natural way to think. ‘I won’t go out today, what happens if I have a flare up away from home?’

Daniel: I always say when I work with people, is that their responses to their pain are totally natural and understandable. Because acute pain is a warning sign; it’s signalling danger. Chronic pain, it’s not, but that’s how our bodies and brains are wired, to see pain as a danger. So therefore of course we’re going to want to protect ourselves, and not put ourselves in danger.

But we have to change that link or belief with chronic pain, that it’s pain but it’s not dangerous. And we can help you to build up your confidence, to manage the pain if you go outside today.

Evans: Clare Daniel.

Diarmuid Denneny is Physiotherapy Lead at the National Hospital for Neurology and Neurosurgery Pain Management Centre in London.

Denneny: The main role of physiotherapy in pain management, whether it’s neuropathic or another type of chronic pain, is around helping people to understand the pain, why the pain lasts, why it hasn’t gone away. And there are often key messages that we would weave into that part of our work, which are around, it’s possible to experience pain even though the body is no longer experiencing damage, or being damaged. And that the amount of pain that we feel doesn’t necessarily equal the amount of injury that our body has, if it was injured, sustained.

So around the understanding of the pain, and in order to do that we need to understand the person and their life, and what’s important to them, and what the pain is stopping them from doing. So that we can start to work out, and I should say we work very closely with psychologists in pain, so we try to work out what’s important to the person who is experiencing the pain, that they are no longer able to do, or that they find difficult to do. And to work out ways to do that, and that’s when we start to think about the physical activity, or the ability to do things. And there’s a reality that most people, by the time they get to meet with a physiotherapist who specialises in pain, will have encountered many physios before that – an average of four or five is a figure I’ve often heard. And so they understandably come somewhat wary or reticent – this idea [of] ‘not another physiotherapist’. Often they’ll have tried to do things with physio and they may have experienced their pain increasing or getting worse, not getting rid of the pain. So the work we do might be to help people to understand that although they’re here because of pain, we might shift our focus more to what they want to be able to do, and look at ways to do that. Which may include looking at movement, and how to move in a way that allows them to build up their activity levels. And activity levels doesn’t necessarily mean going to a gym or doing a prescription of exercises, it can be being able to hang up the washing at home, or to play with their grandkids, or to do their work, which might include an element of physical activity, standing all day, or whatever it is. So we try to explore a bit about activity and exercises, not just going to a gym, but looking at things that fit into their lives.

Evans: I guess something as simple as getting out of bed is an activity?

Denneny: Absolutely, because the centre here is a specialised pain service, so we’ll often see people who’ve been to other pain services first. And their activity levels can be really, really, really affected by pain. Many people will say they have to spend all day in bed with pain, so a starting point might be thinking about sitting up in bed.

Evans: That was physiotherapist Diarmuid Denneny.

Cameron Rashide: It’s been eight years since I’ve stopped working. In the last eight years I literally stayed at home because the pain is too much for me. I stopped going out to coffee shops, and wouldn’t go out shopping on my own – everything online. Literally it was: hospital, home, hospital, doctor, hospital, home.

Evans: Cameron Rashide is a participant on the COPE pain management programme at the pain management centre in London. COPE is group based and focuses on self-management, building upon skills to help people reduce the impact that pain has on their lives.

Rashide: It’s basically living, breathing with your chronic pain. Even though you’re in pain, don’t think that the pain takes you, you take the pain. You have to decide what you can do with it.

Evans: How do you do that?

Rashide: So basically, on this we’ve learnt different skills, we’ve learned to pace ourselves, we’ve learned to cope with feelings and structures. So you have the thought, the feelings and the behaviour. The thought always will be – ‘I can’t do this, I don’t think I can do this’. The feelings will be – ‘ok I want to do this, but can I do this?’. So then the behaviour is actually putting them two in action, and adding the ‘and’ into it, and saying ‘I think I can do this, but if I try this and I try this, I can get to…’ In other words, instead of saying A-to-B, you can’t get there on its own, you need the ‘C’ there, so it’s trying to put them all together.

Learning the skill of just pushing yourself just a little bit, but not too much. Pacing. The golden word, pacing.

Evans: That’s the theory. How are you putting it into practice? And how’s it affecting you?

Rashide: There’s other skills, they’ve asked us to go outside the box that you normally would do since you’ve been in pain. Now this has taught us to practically do something outside the box, like last week my weekly goal was to go to a coffee bar, and I did that. Even though I wasn’t comfortable, I was in pain, but it was enough to pace myself, but not overdo it. So it’s little goals, but achievable goals.

Evans: Well, amongst other conditions, like fibromyalgia, Cameron has neuropathic pain. But there’s a growing body of evidence that people with neuropathic pain don’t do as well on general pain management programmes as those who have other chronic pain conditions. Clare Daniel.

Daniel: I was quite new to pain services and I hadn’t quite realised the difference between neuropathic pain and non-neuropathic pain. And I noted this group of patients, they didn’t quite do as well in the programmes. Some people left the programmes, dropped out, because they just felt as though what we were saying didn’t fit with their experiences. So, ‘I’m different from everybody else in the programme’. And then I began to realise that ‘Well, these are often people with neuropathic pain’. So I looked at the differences between a group of people with non-neuropathic pain and people with neuropathic pain, and actually the main difference is the pacing can help, but doesn’t necessarily help them. Please don’t think I’m saying ‘Don’t pace at all’ because it can be very helpful, but some people don’t feel as though it’s helpful, or it’s unpredictably helpful. And the other thing is the sudden pain that just suddenly comes on. So my gut instinct at that point was that if they can begin to respond differently to their sudden pain, as opposed to what often happens of sometimes literally falling to the floor, or curling up in a ball, if they could stay in the present, remain mindful, learn strategies just to keep them present. Not become very fearful about ‘My pains suddenly there, what’s going to happen?’. Begin to respond, I guess much more gently on themselves, and differently.

Denneny: Asking people with neuropathic pain what would be helpful, and they did express wanting to understand more about the nuts and bolts of the nervous system and how that might be contributing to their pain. So I suppose broadly we agree that it would be helpful to go into more detail on that aspect of the body as part of the programme. So if we call it psychoeducation, we thought that would be useful to include in the programme. Mindfulness uses a certain type of language – if you think about neuroplasticity, which is, broadly speaking, the way that the nervous system is constantly adapting to its environment, and the effect of the environment on the nervous system. So it’s always changing all the time, which is to me tremendously hopeful [laughs].

A lot of the factors that are most helpful for the nervous system, in terms of that neuroplasticity, are around novelty, are around being engaged in a community; so going out and about. They’re around repetition; they’re around focus. And if you think about that in the language of mindfulness, it’s saying the same things really, in terms of what you do. So we thought maybe it would be useful to apply some of those strategies within a programme. So that’s what we set up, and we piloted it for the first three or four weeks [cut off] – 20 patients – and we found that their outcomes, whereas previously they were slightly below what we would have expected, they kind of matched, or exceeded the general scores that we would expect.

Daniel: Astounding in a couple of cases, I remember.

Evans: So basically, the difference between a neuropathic pain management programme and a non-neuropathic pain programme is just how to handle the different ways that pain comes?

Denneny: So around these sudden, severe episodes of pain, feedback almost consistently is actually, the most helpful thing in those moments is to bring my awareness to my breathing. Because it’s a reality with these that they are very sudden, severe, quick, and then they go away almost as quickly as they’ve come. And by the time you’ve got to your medication or other things that might be helpful, it’s settled back down again. So in terms of responsiveness, we’re always carrying our breathing with us all the time, so it’s something that we have access to and we can drop into.

It doesn’t work for everybody, it’s important to point that out, it’s not a panacea or something that is going to work for everybody, but for those who’ve come on the programme, that’s the one thing that they tend to really value and find helpful. So there’s something about strategies and the symptoms that people experience, and then there’s something about the information that we give on it is perhaps more information than you might think is helpful on a general programme. We always give people resources and they’re free to read as much or as little as they want to, or to explore as much or as little as they want to, but we’ve found people with neuropathic pain, they tended to want to know more about what’s going on in the nervous system, how does it change, why does it change, and how does it explain these symptoms.

Daniel: A good pain management programme is about responding to what the people bring. So when I was really interested in setting up a programme for people with neuropathic pain a lot of people said to me, ‘Why are you doing this on diagnosis?’. Of course, I was, because I was separating neuropathic pain from non-neuropathic pain, but that’s not the reason why I was doing it. I wanted to do it because of the differences I observed, so what people were coming with. They could have been diagnosed with anything, but it didn’t really matter to me, it was about tailoring our intervention to what they were coming with.

Evans: This is a very broad question, but what would you consider to be a successful treatment?

Denneny: It’s really down to the person with pain to decide that. In the days of Alastair Campbell I used to think we were trying to help spin things a little bit, by saying ‘Ok you’re here because of pain but we want to focus on what’s important to you’. And in a sense that is what we’re doing, so success would look like somebody achieving the goals that they’d set themselves during their time with us. And maybe not even during their time with us, but having on their last session a very clear ‘I’m not there yet but I know what I have to do, and this is my plan to get there’.

Evans: Establishing what goals a person sets for himself or herself – that can be a very difficult thing because somebody coming to a specialist unit like this might think, well, ‘My goal is to climb Everest’, ‘My goal is to do the London marathon’. How do you sort out expectations?

Daniel: When I first starting working in pain, which was a long time ago, we just focussed on goals and people did find that very difficult, particularly people from different cultures with English as a second language, a goal might mean something very different. More in the last seven to ten years we’ve talked much more about values. And values are some things that are really important to us, and it might be developing, learning, health – they tend to be one word. So it’s about something that we’re continuously aiming towards in our life. We never actually quite reach them, we’re just continuously going towards those.

And then goals are shorter steps in the pursuit of those values, in line with those values. In terms of realistic goals, we talk about short term and long term goals, because as Diarmuid said, when people finish the programme it’s not finished, they will continue, hopefully, to improve in terms of quality of life, reducing the impact of pain. So we’re very clear about short term steps. We do talk a lot about the fact that that might be frustrating to people because they want to get up and run, run before they can walk, literally sometimes. And we do talk very much about realistic expectations. When we talk about goals we talk about SMART goals, the acronym SMART.

Evans: SMART is?

Daniel: So, S stands for specific, so a very specific goal – so not just, ‘I want to swim’. It might be ‘I want to swim two lengths three times a week’. It doesn’t matter. It’s absolutely set by the person with pain. It’s not set by us. So – specific. Measurable, so that you know when you’ve achieved it: so the number of lengths that you want to, for example, swim. Achievable – think about this, is it really achievable with what you’ve set in the timeframe that you’ve set it, ‘Can I swim two lengths by, let’s say six weeks’ time?’. And then the R could be, people often say realistic, personally I think that’s quite similar to achievable. I think relevant’s quite a good one, so ‘Is it relevant to me? Does it fit with my values? Does it fit with what I want to achieve in life? Is it relevant to me?’. And then the T is timeframe or time bound, so ‘When do I aim to achieve this goal by?’. But we’ve also started to talk about that having to be flexible, so we often put an F on the end of SMART [laugh], because people do have high expectations of themselves, they can get very frustrated, life can throw things at them and the measures, or the timeframe that they’ve set for their goals can go awry. And that’s quite normal, that’s life, so we help them to be flexible and think, ‘Well, ok, if you need to push that back a bit, that’s fine’. But what we don’t want is for them to keep pushing back and back and back and never achieve.

Denneny: With pain there’s this idea that doing something that you want to do, that’s important to do, often that you have to do, just because real life means we have to do things, afterwards experiencing an increase in pain. Some people call that boom bust cycle, some people talk about activity cycling, where they do more and then have a period of not being able to do as much. We talk a lot here about flare ups or pain flares. This is terminology, different people have their own preference for what they want to call that. And I suppose for us, working with people with pain, the important thing is to acknowledge that they’re [flare ups/pain flares] a normal part of living with long term pain. They will happen. They don’t mean that things are necessarily getting worse because they are a normal part of the condition over time. And so the challenge is, and what we work a lot on with people, is learning ways to manage, as best they can, so that they get through these flares without having an impact on their ability to manage that sets them back.

Daniel: But also, specifically with neuropathic pain, I think it’s important to help people understand that neuropathic pain, for a lot, not everybody, it can come suddenly. It just suddenly happens with no specific warning. Whereas non-neuropathic pain, not always, but it can just gradually increase and the person knows it’s beginning to increase. So, it’s important that the person recognises that a sudden increase in their neuropathic pain is actually normal. That’s not necessarily related to the boom and bust activity cycling.

Denneny: That is really important, yeah. And again going back to what we do with people, it’s to help try and separate what the pain is doing from what they do day-to-day. Because more than any other group that we work with, people who have neuropathic pain really struggle because often the classic is, ‘Well it doesn’t matter what I do, it’ll either hurt a lot if it’s hurting a lot’, or ‘It doesn’t make any difference’ so much.

So, some of our more, what could be considered traditional strategies for working with people with chronic pain, people who have neuropathic symptoms often struggle, particularly pacing.

Daniel: Yeah, because pacing can be quite, less so nowadays, but it can be quite prescriptive. In the olden days it used to be about people increasing their activity levels, mainly within time. So it might be that you walk for one minute, have a rest, then walk for another minute, and gradually over days, weeks, months, increase that. But some people with neuropathic pain say, ‘Well that doesn’t make sense to me. Regardless of what I do, regardless of how far I walk, even if I’m just sitting down and not walking, my pain will suddenly increase. But sometimes I can walk five minutes and its fine’. So pacing for some people makes less sense, but I think the message therefore has to be a bit more flexible and it’s about, ‘It’s safe to move’. Your pain will increase at times, but then what can you do when it does increase, to help yourself, either mood not suddenly plummet, or giving yourself a hard time.

Denneny: Or stopping doing something because, unfortunately, has it happened at the time you were doing something and you’ve made that link that doing that is what caused it, which isn’t always true.

Evans: That’s physiotherapist Diarmuid Denneny and psychologist Clare Daniel.

For more information about pain services at The National Hospital for Neurology and Neurosurgery Pain Management Centre, including their pain management programmes, put the letters U, C and L, that’s University College London, with the words ‘pain management centre’ into your search engine.

I’ll just remind you as I always do, that whilst we in Pain Concern believe the information and opinions on Airing Pain are accurate and sound, based on the best judgments available, you should always consult your health professional on any matter relating to your health and wellbeing. He or she is the only person who knows you, your circumstances and therefore the appropriate action to take on your behalf.

Now, to end this edition of Airing Pain, what advice would the team give for those who don’t have access to a specific neuropathic pain management programme?

Denneny: There are lots of resources out there in terms of exploring things like mindfulness based pain management approaches they could look at. It’s being flexible with the pacing, or this idea of building up activity, that holding that lightly, if that’s possible. That it’s good to be active just generally for all sorts of other reasons.

Daniel: And safe, it’s safe to be active.

Denneny: It’s safe, yeah, really important.

Daniel: That’s a big important message, ‘I’m not going to do any more damage, I’m not going to do damage’. So a lot of the non-neuropathic principles absolutely apply to neuropathic. And I’d say this to any person with pain, if they’re accessing online resources or self-help materials, about taking what is useful for them.

Evans: And that it’s trusted.

Daniel: Yeah, an evidence based approach is absolutely essential.

Contributors:

Dr Clare Daniel, Consultant Clinical Psychologist, Buckinghamshire Healthcare NHS Trust
Diarmuid Denneny, Physiotherapy Lead at the National Hospital for Neurology and Neurosurgery Pain Management Centre in London
Professor Srinivasa Raja, Johns Hopkins School of Medicine, USA
Cameron Rashide, patient who lives with chronic pain.

More Information:

Neuropathic Pain – Explanations and support at The National Hospital for Neurology and Neurosurgery Pain Management Centre in London.
https://www.uclh.nhs.uk/OurServices/ServiceA-Z/Neuro/PMC/Pages/Home.aspx.

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