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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES Programme no. 1: Pain
RADIO 4
TUESDAY 29TH JULY 2008 2100-2130
PRESENTER: MARK PORTER
REPORTER: BARBARA MYERS
CONTRIBUTORS: IRENE TRACEY
ROSE TURNER
REBECCAH SLATER
PRODUCER: PAULA MCGRATH
NOT CHECKED AS BROADCAST
PORTER
Hello and welcome to a new series of Case Notes. In today's programme I will be looking at recent advances in the understanding and management of pain.
What is the best way of telling if a baby's in pain? Do premature babies experience the same sort of discomfort as older children and adults when doctors stick needles and tubes in them? Two questions a team of researchers from London's University College are trying to answer.
And Barbara Myers visits a hospice to dispel some of the myths that surround the use of strong painkillers like morphine in people who are terminally ill.
But first a bit of neuroscience. One of the major hurdles facing researchers trying to unravel the way our brain handles pain is that it has been impossible to monitor it without interfering with the very things you are trying to measure. But all that changed just over a decade ago with the advent of non-invasive monitors that can pick up tiny changes in electrical activity or blood flow within the brain, without disturbing anything. Now it is possible to see our brains at work, and to watch how they respond to painful stimuli - a process that turns out to be far more complex than we first thought. Professor Irene Tracey is Director of the Oxford Centre for Functional Magnetic Resonance Imaging of the brain.
TRACEY
Right from Descartes time we knew that you put your foot in a fire and it's not until the bell that goes off in your head because it gets the signals from that foot and that flame that you feel that that's a painful experience. The understanding of the complexity, I guess, of what brain regions are involved in that perception has been massively underestimated and until these imaging methods came along even now in basic medical textbooks people are still taught that it just enters the centre of the brain, goes out to one or two different regions, and that's the pain experience. And what we've learnt is that there's a very rich set of brain structures that become active in response, even to the most simple pain experience, and in some ways that is logical because if you just think about any pain that you might experience, be it a pinprick on the hand or putting your finger in a candle flame, and you just think through all the different processes you would go through as you felt that you would locate where it was coming from, you would decide whether it was a pricking or a heat type sensation, you would make a decision as to how intense it was and so you would decide whether you should withdraw your hand or not, you would then remember what caused it and then you would avoid that in future. You would have an emotional reaction to it and if you just think about that, even to a brief stimulus that lasts a second, that can't be processed by one or two different cortical brain areas. And indeed that is the case. So the experiments have been really teaching us the large array of different brain regions that become active and then what we've been doing over the past 10-15 years is what we sort of call dissecting them and labelling specific structures with specific aspects. So which bits are involved in telling you how intense it is, which bits are telling you where it's coming from, which are the bits that are making how your paying too much attention to it and that's making the experience much worse, which bits are your emotional reaction to it - which particularly when we think about chronic pain become very relevant and important for the experience and again can change and amplify and make the experience much worse. So now we've got that sort of labelling of these different regions that provides us opportunities to use them as diagnostic readouts but also as areas to monitor with therapies and to see whether we can modulate them and change them and does that affect then on the experience.
PORTER
You've scanned hundreds, if not thousands, of people here at the centre, is it predictable the response that you get from one person - I mean if you stabbed the heel of one person do you get the same response in their brain as you do 10 other people's?
TRACEY
It's pretty - I mean there are sort of what we call the hardcore set of brain structures that are fairly reliably active, no matter what type of painful stimulus actually you give the individual and across individuals and across people with different cultural and ethnic backgrounds. And so that sort of hardcore set of structures seems to be a very basic important grouping that gives the fundamental ouch this hurts sort of phenomenon. Thereafter there will then be very specific areas that will be quite sort of bespoke to that individual and we tend to think of it now as this unique cerebral signature that you have, or I have, within which will be some core structures that we both share and then there will be other regions that will be on in you and maybe not on in me because for you your particular position right now in terms of how much attention you're paying to your pain, your mood - whether you got up and you're grumpy this morning - you know all these things about the context in which you're experiencing that pain will be different between you and I and that will come into play. And they will basically be represented in different brain regions, so when that painful signal - what we call most susceptive signal - comes into the brain how it's processed will be just slightly different and that is - we tend to sort of say this is what provides the colour or the flavour of your pain experience as opposed to mine. So yes we share structures but then there are unique regions that will be very much unique to you or me and that will provide what's special about your pain experience is different to mine.
PORTER
And is this where this concept of pain thresholds comes - that different people seem to have different thresholds - they respond or react differently to the same stimuli or similar stimuli?
TRACEY
Yeah, well I mean that's really a fascinating area of research right now is what causes a change in people's pain threshold, can it all be explained just on their physiology and their genetics? So when you say to the same pinprick you know that's 9 out of 10 because you're a wooz Mark and I say no, you know for me that's 4 out of 10 - you know am I just lying or is there any reality, objectively, to that difference in our reports? And these experiments have been done with imaging - they've taken large groups of people given them the same stimulus but as you would expect different people have different ratings. And then they've looked at what activates in their brain and they show that indeed people who feel that it's more painful and report it as such for some reason activate a lot more of their brain than the group who say that's not so painful - 4 out of 10 for instance. Now the question is what's driving that difference, can it all be explained by their genes, right at the point that the stimulus is say touching your skin, is that the point that you just send a big signal in from there and I send less? Well there will be for sure an element that is true to that but there'll also be on that journey that that signal is on - right from your skin up to your brain - lots of changes that have been influenced by, again, your cultural upbringing, different experiences you've had, genetics as well, that will change the way your nervous system is wired up and therefore change the way that signal's processed on route to the brain that we think increasingly again explain differences in pain threshold.
PORTER
More from Irene Tracey later in the programme.
Palliative care - tending to the needs of people with serious illnesses from which they will not recover - is an area that has benefited immensely from recent advances in our understanding of pain, and how to treat it. It is a burgeoning speciality with "state of the art" pain management at it's very heart.
Barbara Myers went to Martlett's Hospice in Brighton to meet Dr Rose Turner - a Consultant in Palliative Care.
TURNER
Pain is a consuming distracting state to be in. If you are in pain it's very difficult to concentrate on the things which are truly important.
MYERS
Is it painful to die, is the dying process wrapped around with pain?
TURNER
No. The dying process is not wrapped around with pain but it's sometimes the disease that brings about the dying process that can have been associated with pain. And very often we can do a variety of things to control that pain completely.
ACTUALITY
Okay Ashley, I've got your new fentanyl patches here to replace so if I can just ... okay let's take these ones off now, they look fine, okay. Now I know we're giving you some other extra medication as well, how's it all working the combination?
Umm everything seems to be at the moment balanced out quite well. The patches seem to be doing their job and the extra stuff that's been introduced certainly seems to have calmed me down in the last few days.
MYERS
Ashley Barrett is 44. Surgery for cancer of the oesophagus has left him in a lot of pain and he's been in the hospice for a week where the team are trying different medication to help make him feel more comfortable.
BARRETT
I've been on the fentanyl patches for at least four or five months I would have thought. What other medication? The Oxinorm is the most recent one that I've been introduced to, which is the main drug that I'm taking to control the pain, it's very effective.
MYERS
So at this moment are you free of pain would you say?
BARRETT
I am at the moment yes, yeah, well I don't suppose I'm ever free of pain but at the moment I'm comfortable. That's the best way I can describe it. So if I'm sitting nice and still and I've had my medication, which I have about half an hour ago, then yeah I'm comfortable.
MYERS
The stronger analgesics do seem to be helping Ashley and Dr Turner has no hesitation in prescribing them.
TURNER
Patients are very frightened when they hear about the use of morphine but it is in the context of pain management an enormously safe drug. Quite different when used for the right reasons from the drug which is abused for all the wrong reasons.
MYERS
Used in a therapeutic setting it's safe and effective, not addictive?
TURNER
Not addictive at all and if, as often happens over time, the pain gets greater and the patient needs more morphine it's not because they're addicted to it it's because their need is greater and to set the balance between pain and pain control we need to lift the dose. Dame Cicely Saunders taught us very early on in the modern hospice movement that when you're treating chronic cancer pain the solution has to be continuous medicines, medicines taken regularly, not medicines taken to chase the pain away. So what we're looking for is control so that we have the patient ahead of their pain.
BARRETT
At night time sometimes it can be a bit painful because obviously you want to sleep, so you wake up in the night in discomfort and that's always the worst time because you - I guess the mind starts ticking over and it's difficult to get back to sleep.
MYERS
There's a lot going on, isn't there, when you've got an illness and when you've had operations and so on so partly physical but it's also how you're feeling about things I expect.
BARRETT
Oh there's a tremendous amount going on inside your own head, you know, obviously with families and children, everything, so that all adds to anxiety, which I think, you know, the anxiety combined with the pain is a bad combination. So trying to control that is not an easy thing.
MYERS
And that's the limitation of analgesia. As Dr Turner says there's no prescription to cure heartache. Fortunately there's more to hospice care than drugs.
TURNER
Comfort, if not pain relief, can come in many different forms and therapy of touch and company is a very comforting thing. A very skilled nursing auxiliary, knowing exactly how to position a painful arm, can actually bring about a short interval of comfort and that is a blessed relief.
MYERS
All that said are there some patients whose pain is really very difficult to treat and despite all the best efforts and all the drugs in the armamentarium you haven't got the answer for them?
TURNER
There are always the occasional unfortunate patient where the pain is difficult to manage. I'm asked to see the most difficult of cases with the most complex issues to find an answer to. Thankfully it is very, very rare that we see a patient actually dying in pain.
PORTER
Dr Rose Turner talking to Barbara Myers at the Martlett's Hospice in Brighton
Back in Oxford at the FMRI Centre Professor Irene Tracey was explaining what is required to monitor how the brain responds to pain. Starting with her pride and joy - the FMRI scanner.
TRACEY
So it's no different than a standard clinical MRI machine that people would be used to going to have structural pictures and we're just collecting the data in a slightly different way where we're looking at the change in the sort of image intensity as it relates to the change in the amount of oxygen in the blood, you know when the brain works and the cells start talking to each other they get hungry and they demand oxygen and glucose, so blood rushes there to deliver it and what we're doing with this functional imaging is picking up the increase in blood flow to that particular area of the brain that's working. And what the blood's doing is just feeding those cells so they can keep working, keep firing, keep being important for processing pain.
PORTER
Which brings me on to the next question: they're in the scanner, you've got their brain under scrutiny, then you do things to them to see how they respond to pain - what sort of things are you doing to them?
TRACEY
Well we have an array of different painful procedures that we can inflict on the individuals. The most common one, that people will be familiar with, would be a thermal pain experience - so we can give them noxious heat, we can give them noxious cold - something that's very, very cold, like burning, basically burning or freezing them. Obviously we're contained and constrained by the ethical limitations that subjects are willing to comply with and our committee gives us approval for ...
PORTER
So thermal you do what to them?
TRACEY
We generally give them a painful thermal stimulus say about 49-50 degrees, people can think about, you know, the point - if you put your finger in a hot cup of coffee and the point at which you think you know this is really painful and I'd like to take it out, we would probably require them to keep it in there for another three or four seconds. We'll have them rate that and we tend to like people to have a pain experience sort of 7 out of 10 - that sort of moderate to strong pain.
PORTER
Now you've got a bank of machinery here - you've got a screen in front of the patient, there's a - unless I'm very much mistaken - a projector, so you can do all sorts of different things to them.
TRACEY
All sorts of things, we can change people's - whereby projecting different instructions we can distract people and have them be distracted whilst we're giving them pain and as you would expect that changes what they say, how painful it is, and we show why - why is it when you're not thinking about the pain it doesn't hurt so much and we show where that interaction works. We can also use some different pieces of equipment that you see here to manipulate people's anxiety levels or depression levels and we can make their mood very slow - one of the tricks we use is maybe we'll play Prokofiov twice as slow as normal - and trust me it really makes you quite miserable. When you've done that you give them the same pain and it feels much worse now. So those are the sorts of tricks we use.
PORTER
And sitting in front of you here is a box that I've been looking at for a while because I suspect I'm going to be on the receiving end, with the pinprick written on the top.
TRACEY
That's right, this is one of our favourite pain devices, we're not thinking about thermal pain now, we're thinking about mechanical pain. So what we have here - an array of different pinpricks basically that have different forces. So I can make the pinprick quite light and I can make it quite painful.
Well let me start with the really light one which you would barely - barely perceive. So I'm going to put this on your hand and just tell me whether you can even feel that?
PORTER
Hardly.
TRACEY
Hardly, yeah, so that's ...
PORTER
So it doesn't hurt.
TRACEY
It doesn't hurt, so this is on this - one of the main fibre systems - the A delta system - and that's just a mechanical input that's very light, you can barely feel it. But as we take the force of the pinprick up to this level - I'm hoping, Mark, you'll find that now...
PORTER
Yeah I can feel that, yeah.
TRACEY
So on a 10 point scale where 10 is excruciating and 0 is no pain.
PORTER
Oh 2 or 3 - 2.
TRACEY
Two yeah. And then we can take it up just a little bit more and give you a slightly bigger one and that now?
PORTER
And I think that proves the point.
TRACEY
That proves the point. So that's a very common device that we'll use to stimulate one of the main pain fibre systems.
PORTER
What's the brush for?
TRACEY
Well the brush - again this is a system which again if I stroke you now with that, that will hopefully be quite pleasant and that is activating the other main fibre system the body has which we call the A Beta and that's normal touch. Now what's interesting is when people have a chronic pain disorder, say a nerve injury pain, normal touch like this or putting on their clothes or lying under their bedclothes is burning pain or they find this very painful. So one way that we try to understand that is to use the active ingredient of chilli peppers - capsicum - which we can rub on to the skin and after about an hour that capsicum causes these plastic changes in your brain, in your spinal cord. Now the reason we're allowed to use it is they only last for a few hours and then they all reverse, so it's ethically okay.
PORTER
People would be familiar with that as well, if you get chillies on your hand or in your mouth it does alter your perception.
TRACEY
It does and I'm sure that many people have chopped chillies and then rubbed their eye and it's really, really sore. And the reason you describe chillies, even when you eat them, as heat is because the actual [indistinct word] susceptor, the sort of pain receptor, that the chilli pepper binds to is the same receptor that heat communicates to. And then when I take this brush now and you've got - and you've had that chilli pepper for an hour, if I rub where the chilli pepper is that'll be like burning sunburn, just like people have experienced sunburn and then they go into a shower and a pleasant warm stimulus is now really quite painful. But the interesting thing is around the area of the chilli pepper, if I touch it, you will also report that as painful. And that's because that chilli pepper has changed your spinal cord in your brain because of this plasticity that's occurred. And that's what we image. So we don't often image the main area where the chilli pepper is, we image these remote areas because they are giving us information about the changes in the central nervous system that's occurred, that mirror a lot of changes that occur in chronic pain.
PORTER
Irene Tracey.
FMRI technology may be useful for seeing what happens inside our heads, but you don't need a high tech scanner to know when someone is in pain - you can see it in their expression, or they can tell you. But what if you are working in a special care baby unit that caters for some of the most premature babies born in the UK? They can't tell the doctors or nurses looking after them, or their parents, if something hurts - and their reactions, which are currently what we depend on to see if they are comfortable, may not be that reliable either. Neuroscientist Rebeccah Slater and her team at University College London are studying how premature babies respond to pain.
SLATER
Facial expression change is one of the key indicators that doctors and nurses would use. For example, how much they screw up their eyes, how much they flare their nostrils and how much their brow bulges are some good examples. They also look at some of the physiological changes, such as change in heart rate or saturation. And quite often these measures are used to try and assess pain in these infants.
PORTER
And by saturation you mean that's the amount of oxygen in their blood?
SLATER
That's right yes.
PORTER
Which would go down if they're in pain and holding their breath?
SLATER
That's the idea. Quite often heart rate will go up when you do something painful to a baby and their oxygen saturation would go down.
PORTER
So that - I mean that sounds quite an accurate - I mean a set of three different things they're looking at there - it sounds quite sensible.
SLATER
It is one useful way of looking to see whether a baby is responding to pain but these measures could be mediated at a really low level of the nervous system, some of them could be motor responses. If you really want to understand pain processing you need to look in the brain and at higher levels of the nervous system because that's where all the kind of later processing would take place.
PORTER
So if using simple cues isn't going to give us the full picture what might?
SLATER
One thing we could do is look in the somatory sensory cortex and see whether that part of the brain becomes active when an infant has a painful procedure.
PORTER
And this is the part of the brain that sort of amalgamates and deals with all the pain signals?
SLATER
It's one of the areas that would be active in adult if they were in pain. And the more an adult reports pain the more activation that this area has. So we think it correlates quite well with our pain perception. So in babies we use a technique called near infrared spectroscopy, it's a bit like FMRI in that it measures hemodynamic changes but you can actually use it while the baby remains in hospital and in intensive care, so they don't need to go into a large scanner.
PORTER
So this is a cot side monitor?
SLATER
Absolutely yes, all this can be done while the babies remain in the intensive care environment.
MARKS
My name's Susanna Marks and this is my gorgeous baby daughter Amelia. She arrived at 32 weeks and she's been in hospital for eight weeks, so far since then. She was in both intensive care and special care. Everyone - you know it's a really, really fantastic team who work down there and well I suppose you're always concerned that - whether she is in pain, I mean they do most of the blood tests when you're not around - they do them at night - I think obviously purposefully, so you do wonder how they - how they do react.
PATTEN
I had a premature baby myself and it was just get this baby well.
PORTER
Debbie Patten is a sister on the special care baby unit and part of the research team.
PATTEN
A baby can have up to about 30 procedures a day, depending on the gestational age, so that could mean a lot of procedures a day. Vena puncture, cannulation - that's giving drugs - a line into its umbilical cord, into the main artery, into the vein - well it's the doctors really that have the main task of puncturing the baby, if you like. There's no other word for it, you know, we have to do these procedures and I suppose you get into a mode of yes the baby feels pain, we know it feels pain, whether it's grimacing or not, from our study but however what do you do, you have to save its life.
SLATER
So we tested this a number of years ago to see whether if the infants were having a painful experience whether this area of the brain was activated and we found that it was. And even in the youngest infants that we studied they also showed activation in this area. So all the infants that we studied showed that they were able to process this information at the higher levels of the cortex.
PORTER
Which would suggest that they're feeling pain in the same way that you and I would feel pain if we had something - a needle stuck into us?
SLATER
I don't know - we only looked in one area of the brain which is one of the first areas where this information is processed - so we don't know the extent to which a baby will feel pain because they obviously can't tell us but it definitely suggests that you're able to have processing at the higher levels.
PORTER
And the implications of that finding are what?
SLATER
So once we were able to establish that you could actually get cortical activation following a painful procedure we wanted to see how well the traditional pain assessment measures compared in their scores with the measure that we had. So more recently we took another population of infants, we measured the brain activity and we also used a clinical pain score which doctors and nurses might traditionally use to assess infant pain and we wanted to see how well these two measures correlated.
PORTER
And as a clinician one would hope that they correlated very well but was that your finding?
SLATER
Well that's exactly what you would hope. And what we actually found was that there was a good correlation overall and that generally if the activation in the somatory sensory cortex was large then you also got a higher pain score. But when we actually broke down the pain score and we separated out the parts that corresponded to the facial expression and the parts that corresponded to the physiological activity we found that the facial expression was actually the best indicator compared to the other measures. So perhaps we could use facial expression more than say some of the other measures that didn't correlate so well.
MARKS
Because obviously you don't know whether - you know whether - I just thought it would be interesting because I know when she has things done to her I notice that she doesn't appear to be in pain so I didn't know whether that was transmitted to what was happening in her brain activity as well, so I just thought it would be interesting. And actually when she was going through it she looked - she was as chilled as ever.
SLATER
I mean if you were to just use these behavioural measures alone the pain that these infants are experiencing might be underestimated and in that case they might be less likely to be given pain relief when they might need it. Often the kind of pain relief that these babies are given includes swaddling the infant, talking to the baby and perhaps providing sucrose for them. But in adults and small children this would be completely unacceptable. So really we want to find better ways and better pain relief for these babies.
PORTER
And presumably you can use your technology to monitor the effectiveness in trials of those sorts of pain relieving methods?
SLATER
That's right and that's what we would like to go on to do, to try and see which methods of pain relief can dampen down this activity in the brain the most.
PORTER
Rebeccah Slater.
Most of Rebeccah's work is based on responses to painful stimuli of short duration - like having a needle stuck in your heel - but it is chronic pain like arthritis and sciatica that makes up the lion's share of my workload in general practice. And while acute pain may help protect us from harm, there is growing evidence that chronic pain serves little useful purpose. Indeed it may actually take on a life of its own and permanently alter the nervous system. Professor Irene Tracey again.
TRACEY
In the transition from acute pain being a very good thing, telling you you've hurt yourself you should look after it until it gets better, is in that transition to chronic pain where it doesn't get better and the pain's still there three, four, five months later, years later, there is a set of changes that occur in the central nervous system - the spinal cord and in the periphery - that if you like maintains that pain signal. So now it's not providing a warning symptom anymore it's basically a symptom of something's gone wrong. And that has really come from some of these observations from imaging and other types of experiments that there seems to be something that's very specific about chronic pain that's different to acute pain, that the maintenance of it shares changes that again are sort of what we call plastic changes, changes that amplify the inputs. We tend to think of plasticity as good - say post stroke - the nervous system can become plastic, adapt if you like and change and take over function to provide benefit back to the patient. We tend to think of plasticity as bad in chronic pain because what it tends to do is if you like hardwire on this system that keeps the signals both on and amplified.
PORTER
So the brain actually adjusts to the constant input of pain?
TRACEY
Yes, that's right. So we think of plasticity as a sort of spatial rewiring or melting, if you like, and sort of hardwiring on of the system but we also use it in the context of amplification as well so that these plastic changes can also turn up the volume, just like on a hi-fi you'd turn the volume up of the actual signal coming in, so the experience is more painful. And these are new ideas that force us to potentially redefine chronic pain as a disease in its own right. And that I think changes everything both people's attitudes, how you might want to think about diagnosing it and certainly how you'd think about managing it and treating it.
PORTER
Prof Irene Tracey talking to me at the Oxford Centre for Functional MR Imaging of the Brain.
Don't forget you can listen to any part of the programme again - and set-up a weekly podcast so you need never miss an episode in future - by visiting our website bbc.co.uk/radio4.
Next week - weather permitting - I'll be heading outside to explore some of the hazards that lie in wait for Britain's intrepid gardeners - everything from tetanus to potentially lethal compost heaps.
ENDS
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