Information & Resources

Find information and resources to help manage your pain.

Get Help & Support

Find the tools you need to
help you manage your pain.

Get Involved

Help make a real difference to people
in the UK living with chronic pain.

About Us

Find out about Pain Concern and how
we can help you.

Transcript – Programme 68: The Brain and the Genes

The sci­ence behind pain and its treat­ment, and why under­stand­ing it matters

To lis­ten to this pro­gramme, please click here.

If some­one steps on your toe, your toe hurts – sim­ple as that, right? Wrong! Pro­fes­sor Rolf-Detlef Treede explains how the brain and ner­vous sys­tem make pain and why we can feel pain in a part of the body that hasn’t been harmed. It’s not just a ques­tion of good sci­ence, Treede argues – bet­ter under­stand­ing will decrease dis­crim­i­na­tion against peo­ple in pain.

Genes also have a role to play in the sto­ry of pain, says Pro­fes­sor Ana Valdes. Her research is help­ing to explain why some peo­ple devel­op con­di­tions such as fibromyal­gia, migraine or rheuma­toid arthri­tis and oth­ers do not based on dif­fer­ences in our make­up at the mol­e­c­u­lar lev­el. Even our psy­cho­log­i­cal respons­es to pain are affect­ed by dif­fer­ences in the ner­vous sys­tem. Valdes believes these more sophis­ti­cat­ed approach­es to pain offer hope of effec­tive treat­ment in the future.

Issues cov­ered in this pro­gramme include: Neu­ro­science, genet­ics, ner­vous sys­tem, risk fac­tor, fibromyal­gia, cat­a­stro­phiz­ing, brain sig­nals, pain per­cep­tion, neu­ro­path­ic pain, anti­de­pres­sants, comor­bidi­ties, biopsy­choso­cial, noci­cep­tive, hyper­sen­si­tiv­i­ty, pain mem­o­ry and CBT: cog­ni­tive behav­iour­al therapy.

Paul Evans: Hel­lo, I’m Paul Evans, wel­come to Air­ing Pain, the pro­gramme brought to you by Pain Con­cern the UK char­i­ty pro­vid­ing infor­ma­tion and sup­port for those of us with pain and health­care pro­fes­sion­als. This edi­tion has been fund­ed by a grant from the Scot­tish Government.

Pain by def­i­n­i­tion is sub­jec­tive. To try to mea­sure pain objec­tive­ly is real­ly a lit­tle bit of a stu­pid question.

Paul Evans: [Laughs] Well, even the most stu­pid ques­tions have good answers. Now, are we pre-dis­posed to devel­op­ing chron­ic pain, does it run in fam­i­lies? Ana Valdes is Read­er and Asso­ciate Pro­fes­sor at the Uni­ver­si­ty of Not­ting­ham. Her research is focused on find­ing the epi­demi­o­log­i­cal (that’s the study of how often and why dis­eases occur in dif­fer­ent groups of peo­ple) and genet­ic risk fac­tors that con­tribute to a dis­ease. So, is there a genet­ic fac­tor to chron­ic pain?

Ana Valdes: We think there is and there are some pub­lished stud­ies which show for exam­ple that for chron­ic wide­spread pain, there is a con­tri­bu­tion from genes and there is a con­tri­bu­tion also to things like migraine to severe migraine. Some of it is famil­ial, some of it is not famil­ial but it does­n’t mean if you have this one gene you’re going to get chron­ic pain. What hap­pens with all these com­plex traits, as is chron­ic pain, which is very com­plex clin­i­cal­ly – it’s com­plex in terms of treat­ment – and the caus­es are com­plex. But if we… more than try­ing to under­stand if it runs in fam­i­lies, which is impor­tant – I guess it’s impor­tant if it runs in fam­i­lies – but more than that, we’re try­ing to under­stand by using genet­ics as a way of inves­ti­gat­ing the mol­e­c­u­lar caus­es of pain, hop­ing that by under­stand­ing what are the mol­e­c­u­lar caus­es of pain, we might be able to treat it bet­ter or to diag­nose it ear­li­er or to diag­nose it better.

So it’s not just about find­ing the gene for pain, but find­ing which mol­e­c­u­lar pat­tern is it, what it changes. Is it in your nerves? Is it in your mus­cles? Is it in the brain and in which part of the brain? Is it some­thing that’s real­ly inher­it­ed? Is it…? You know, so that’s the kind of ques­tions that we are try­ing to address.

Evans: If those are the ques­tions, then what are the answers?

Valdes: The answer is that it’s ear­ly days. Though we do know, for exam­ple, that peo­ple with arthri­tis pain, say from their knee, you can have a very unhealthy knee when we look at your x‑ray but you have no pain. Some­one else has a knee as unhealthy, or even less unhealthy, than yours and they have very severe pain. And what we’re find­ing is that some of these genet­ic vari­ants involved in periph­er­al pain, so in the pain that comes from your body, how you feel it can actu­al­ly influ­ence the risk of you hav­ing painful osteoarthri­tis or not hav­ing painful osteoarthri­tis, giv­en the same amount of joint damage.

But also we are find­ing peo­ple who have had a surgery and are hav­ing this nerve dam­age type of pain, we find that some of the mol­e­cules asso­ci­at­ed with that, some of the genes asso­ci­at­ed with that, are brain genes that are relat­ed to synap­tic plas­tic­i­ty. One of these genes we find seems to go also in asso­ci­a­tion with fibromyal­gia, a weak­er cor­re­la­tion with fibromyal­gia. So maybe we are find­ing some of the mol­e­cules that are impli­cat­ed in chron­ic pain.

Evans: I have fibromyal­gia and I can remem­ber twen­ty-five or so years ago, being asked ques­tions like ‘is there depres­sion in the fam­i­ly? Is there alco­holism in the fam­i­ly?’ because there may be a link, not through alco­holism, but through the mech­a­nisms that involve that and depression.

Valdes: Well we do find, I mean I’m not look­ing direct­ly at depres­sion, as I say – I’m only look­ing at fibromyal­gia. Do the results we find for this type of spe­cif­ic pain from patients after surgery… is it sim­i­lar to some of the things we see in fibromyal­gia? But in our case we are look­ing at some­thing called ‘cat­a­stro­phiz­ing’, which is how an indi­vid­ual copes with pain. We ask a per­son ques­tions like ‘how often do you feel that you can­not go on with pain?’ Or ‘do you feel your pain is real­ly terrible?’

And the more they have these cat­a­stro­phiz­ing traits, the worse their pain. It is very relat­ed to depres­sion and anx­i­ety. Their pain is worse, their qual­i­ty of life is worse and their sleep qual­i­ty is worse. So, that is a kind of psy­cho­log­i­cal trait, if you want, but what we find is that the same genes that are asso­ci­at­ed with the pain, first the cat­a­stro­phiz­ing trait is actu­al­ly – if you look in the brains of these peo­ple – cor­re­lates with fea­tures in the lim­bic cor­tex in spe­cif­ic parts of the brain. So that already tells us, yes, it’s in your brain, but that does­n’t mean if I give you a slap on the face, you can get over it. There is some­thing phys­i­o­log­i­cal­ly going on.

And then, final­ly, the same genes that are asso­ci­at­ed with these nerve dam­age types of pains are also asso­ci­at­ed with cat­a­stro­phiz­ing, or this fea­ture of pain, where peo­ple feel that they can­not go on with the pain and this is ter­ri­ble. So pain is an extreme­ly com­plex trait to study with many com­po­nents to it. We’re not say­ing genet­ics is going to be the cure for chron­ic pain, but we feel we can con­tribute a lit­tle bit to under­stand it better.

Evans: That was Ana Valdes of Not­ting­ham Uni­ver­si­ty. So what is going on in the brain to make us expe­ri­ence pain? Pro­fes­sor Rolf-Detlef Treede of Hei­del­berg Uni­ver­si­ty, Ger­many is a neu­rol­o­gist, that’s to do with the ner­vous sys­tem, the brain, the spinal cord and the nerves. So to take a very sim­ple exam­ple, if some­one steps on my toe, why do I feel pain?

Rolf-Detlef Treede: You give a very good exam­ple. It seems to be very sim­ple that when some­one steps on your toe, your toe hurts. This actu­al­ly is very com­pli­cat­ed neu­ro­bi­ol­o­gy. You have sen­sors in your toe that detect there’s dam­age and they gen­er­ate sig­nals that are sent up to the brain along cer­tain path­ways. Then the brain recog­nis­es this activ­i­ty and the brain has to have some con­cept of hav­ing a body. So the brain then projects this feel­ing into that part of the body where the brain thinks the infor­ma­tion is com­ing from.

In the case of some­one step­ping on your toe, the infor­ma­tion is com­ing from the toe, the brain thinks it’s com­ing from your toe, so your toe hurts and this is where the dam­age is. How­ev­er, you can also have the brain thinks it’s com­ing from the toe when the dam­age is com­pres­sion of a nerve from a bulging disc in your low­er spine. The sig­nal will end up going to the brain, on the same path­way or it could be gen­er­at­ed by the toe itself or some­where along the path­way, in this case close to the low­er spine or it could be gen­er­at­ed in the brain itself. In all these cas­es it’s very dif­fi­cult for the brain to tell where the infor­ma­tion is com­ing from. There’s a term which is called ‘pro­jec­tion’, so pain is pro­ject­ed to some part of the body, this is where we feel it and very often this part is exact­ly where we have the injury, then every­thing is easy.

Evans: And that makes sense does­n’t it because if some­body has stepped on my toe, the brain iden­ti­fies that the toe has been stepped on and sends the pain down there, which makes me move my foot.

Treede: Yes, yep. It’s fig­u­ra­tive to say ‘send the pain down there’. Actu­al­ly, I have slides on that which looks like the pain is sent down there, of course although in real­i­ty, this is entire­ly hap­pen­ing with­in the brain. But I think it’s a nice con­cept of say­ing the brain has a lit­tle pup­pet of our­selves and sends the pain down there, where it thinks it’s com­ing from. There are many ways of hav­ing a mis­lo­ca­tion. And I think pret­ty soon there will be an anniver­sary of Hen­ry Head, describ­ing head zones of pain refer­ral of infec­tions of inter­nal organs. So there’s a cer­tain reg­u­lar­i­ty, so when your colon has been dam­aged, this is mis­pro­ject­ed but it’s mis­pro­ject­ed accord­ing to a cer­tain rule and these rules are known to med­ical specialists.

So when a patient reports a cer­tain type of back pain, the med­ical spe­cial­ist should have the idea that this may be from the colon. Many peo­ple know pain in the left arm could be relat­ed to the heart or the gall blad­der to the left shoul­der and things like that. It’s very impor­tant to acknowl­edge that, in a sim­ple sit­u­a­tion where you have an injury and it hurts where the injury is, it’s the same com­plex mech­a­nism. And the rea­son it’s impor­tant to acknowl­edge that is because many patients feel pain in parts of the body where there’s no injury at all.

Now some peo­ple may think those patients are crazy because we think the brain always localis­es the pain to an injured body part but that’s actu­al­ly not the case. There­fore it’s impor­tant to know this, so you do not dis­crim­i­nate against peo­ple who report pain in the body part where there is no injury. It only means that the mech­a­nism of that pain is not com­ing from an injury to that body part.

This takes me to neu­ro­path­ic and nerve pain because in neu­ro­path­ic pain it’s always the case that the part of the body where the patient reports the pain has no injury, because neu­ro­path­ic pain is gen­er­at­ed by the alarm sys­tem itself. We call it ‘the noci­cep­tive sys­tem’, the sys­tem that nor­mal­ly responds to injury and the sys­tem can also just gen­er­ate activ­i­ty on its own. If you have a car alarm sys­tem you know what I’m talk­ing about – alarm sys­tems can go off with­out an exter­nal cause and the alarm is real and you have to do some­thing to switch it off and the same is true of nerve pain.

Evans: Well, the expla­na­tion sounds easy [chuck­les]. How does one turn it off?

Treede: Ah ok, that’s the more dif­fi­cult part. Maybe I should give an his­tor­i­cal per­spec­tive of neu­ro­path­ic pain and its treat­ment. There was the term ‘intractable pain’ in the past cen­tu­ry and you can look at the sit­u­a­tions that are called ‘intractable pain’, they’re basi­cal­ly neu­ro­path­ic pain con­di­tions. Phan­tom limb pain was some­times count­ed as such. In the con­text of back pain when there had been surgery, that [was] like­ly to cause addi­tion­al dam­age to nerves, failed back surgery syn­drome and many oth­er con­di­tions, pain from dia­bet­ic neuropathy…

So, there was this term intractable pain. In the 1990’s some lit­er­a­ture came out – or some­what ear­li­er – called ‘how to treat intractable pain’. Which sounds like a con­tra­dic­tion in terms, but it turned out that peo­ple had dis­cov­ered some ways of actu­al­ly help­ing those patients that do not respond to the ordi­nary analgesics.

Why was it called intractable pain? Because nor­mal non-steroidal anti-inflam­ma­to­ry drugs did­n’t help much and also opi­ods at that point were con­sid­ered not to be help­ful. So the stan­dard treat­ments that were also giv­en out for post-oper­a­tive pain and can­cer pain, did­n’t real­ly work. Now treat­ing intractable pain had, I think, two his­tor­i­cal back­grounds, one was com­ing from this cog­ni­tive behav­iour­al ther­a­py back­ground, which we would inter­pret as util­is­ing learn­ing mech­a­nisms for the ben­e­fit of the patient, which is log­i­cal because some intrin­sic learn­ing mech­a­nisms actu­al­ly also cause the pain. The oth­er part is phar­ma­co­log­i­cal treat­ment that was com­ing from two areas that seemed to be not very much relat­ed to pain. So the obser­va­tion was that anti­de­pres­sants were some­times help­ful and anti­con­vul­sants, drugs designed to treat epilep­sy, were some­times helpful.

With respect to the antiepilep­sy drugs, the mech­a­nism at first glance is rel­a­tive­ly straight for­ward. Epilep­sy is too much elec­tri­cal activ­i­ty, speak­ing very sim­ply, and chron­ic pain means elec­tri­cal activ­i­ty in the brain, so if you can some­how inter­fere with the elec­tri­cal activ­i­ty, it’s not total­ly implau­si­ble that it might work.

Evans: Your turn­ing down that elec­tri­cal activity.

Treede: Turn­ing down that elec­tri­cal activ­i­ty, damp­en­ing down that elec­tri­cal activ­i­ty. Of course not every­thing that turns down elec­tri­cal activ­i­ty works against epilep­sy and not every­thing works against pain. Clear­ly, you have to have the clin­i­cal tri­al data to see what works. Some of the anti­con­vul­sants work and some don’t. So these two parts, epilep­sy and neu­ro­path­ic pain have some things in com­mon but some are also different.

And the oth­er part, anti­de­pres­sants, has two com­po­nents: peo­ple who are depressed often have pain as a part of clin­i­cal pic­ture of depres­sion and, in turn, if you have chron­ic pain, this real­ly dete­ri­o­rates your mood. So any­body with chron­ic pain ful­fils some of the cri­te­ria of depres­sion and there­fore, one of the con­cepts was that maybe we’re treat­ing the depres­sion and this helps the patients. This prob­a­bly con­tributes but it’s not the entire sto­ry as these drugs can be ben­e­fi­cial to peo­ple who aren’t depressed. The anti­de­pres­sants can inter­fere with cer­tain neu­ro­trans­mit­ters systems…

Evans: So the neu­ro­trans­mit­ter sys­tems are the neu­ro­trans­mit­ters, the sys­tems where mes­sages pass from one cell to anoth­er in the brain.

Treede: Yes, that’s right. We have talked about elec­tric activ­i­ties, so the elec­tri­cal sig­nal stays with­in one neu­ron with­in a nerve cell that can trav­el a long dis­tance, almost along the entire body from your toe to your brain stem, in the extreme case. But if you want to get a sig­nal from one cell to anoth­er, you need some chem­i­cal sig­nal and there are some neu­ro­trans­mit­ters – actu­al­ly, there is rel­a­tive­ly a long list of neu­ro­trans­mit­ters – there are some that basi­cal­ly trans­mit exci­tary sig­nals, and that’s glu­ta­mate. And that’s involved in pret­ty much involved in every­thing, so it’s very dif­fi­cult to treat any spe­cif­ic dis­ease based on glutamate.

There are some oth­er neu­ro­trans­mit­ters that have more restrict­ed rules, two of these trans­mit­ter sys­tems are involved in sig­nals that are sent up from the brain stem to the spinal cord and mod­u­late the sig­nal trans­mis­sion in the spinal cord. And the tra­di­tion­al label­ing has been a descend­ing inhi­bi­tion, so that the body can inhib­it the pain sig­nal by the brain stem con­trol­ling how much input the brain gets. Here we have two trans­mit­ters, sero­tonin and nora­dren­a­lin, which are also impor­tant in the con­text of depres­sion. So, the anti­de­pres­sant drugs mod­u­late the actions of sero­tonin and nora­dren­a­lin and when you mod­u­late those actions, this can also be ben­e­fi­cial for pain.

Evans: Those drugs are the SSRIs, the sero­tonin selec­tive re-uptake inhibitors?

Treede: It’s a very good point for you to bring this up because they are the ones where the two fields again have sep­a­rat­ed. It’s like with epilep­sy, there’s some over­lap, neu­ro­path­ic pain and epilep­sy, but also some dif­fer­ences. The same is true with respect to anti­de­pres­sants and neu­ro­path­ic pain treatment.

The very clas­si­cal anti­de­pres­sants, the tri­cyclic anti­de­pres­sants, like amitripty­line – off-patent for many years – is very non-spe­cif­ic, it does many things. Now for the treat­ment of depres­sion, peo­ple have noticed that to real­ly focus on the sero­tonin part, this is very help­ful, because then you have few­er side effects, but you can still get the ben­e­fit. So these sero­tonin selec­tive re-uptake inhibitors are more mod­ern and bet­ter anti­de­pres­sants and they don’t help against pain, because for pain the nora­dren­a­lin side is more impor­tant. So, that seems to be the com­mon denom­i­na­tor –those anti-depres­sants that also influ­ence the nora­dren­a­lin side, they are also good against pain.

Evans: Many peo­ple are pre­scribed anti­de­pres­sants for their neu­ro­path­ic pain, so does that mean that depres­sion is the illness?

Treede: No, because we know that in neu­ro­path­ic pain patients, anti-depres­sants can help the pain even when they’re not depressed. Hav­ing said that, we have this con­cept which is called ‘comor­bid­i­ty’, so a cer­tain per­son can have more than one dis­ease and it’s very fre­quent that a per­son who has a chron­ic pain could also have a depres­sion. In that case maybe as a sec­ondary con­se­quence of the chron­ic pain, because depres­sion is a mood dis­or­der and clear­ly chron­ic pain dete­ri­o­rates the mood. Then what clin­i­cians often do, when they have the choice of dif­fer­ent phar­ma­co­log­i­cal treat­ments and each treat­ment address­es more than one thing, they have to tai­lor this to the indi­vid­ual patient. So if a patient has a chron­ic pain that has dete­ri­o­rat­ed the mood of that patient, then you would go for a med­ica­tion, an anti­de­pres­sant that helps the depres­sion and the pain.

Anoth­er typ­i­cal comor­bid­i­ty – when you have chron­ic pain you don’t sleep very well and actu­al­ly you sleep much worse than patients with a sleep dis­or­der. Some of the med­ica­tions that are used against neu­ro­path­ic pain improve sleep. So, if you have a patient that has a major sleep prob­lem and chron­ic neu­ro­path­ic pain, you would go to that drug class that also improves also the sleep con­di­tion. Again, if you have a patient that has their comor­bid­i­ty of depres­sion, you go for the anti­de­pres­sant, if you go for the comor­bid­i­ty of sleep dis­tur­bance, then you go for the med­ica­tion that helps sleep.

The same log­ic applies to all the oth­er drugs, because the old­er drugs also have mul­ti­ple mech­a­nisms and this is real­ly the task of the pre­scrib­ing doc­tor, to take into account the entire sit­u­a­tion of the patient. The patient does­n’t just have one diag­no­sis, usu­al­ly they have more than one thing and even if the dete­ri­o­rat­ed mood does not yet ful­fil the clin­i­cal diag­no­sis of depres­sion, it might be help­ful to improve the mood, one way or another.

I should­n’t end this with­out say­ing that med­ica­tions aren’t every­thing. The treat­ment is always mul­ti-modal and that means there has to be some behav­iour­al, psy­cho­log­i­cal com­po­nent to it, usu­al­ly some ele­ment of exer­cise or phys­i­cal therapy.

Evans: Yes, the term comor­bid­i­ty, no per­son is one ill­ness, in fact, a per­son is not an ill­ness, a per­son is a person.

Treede: Absolutely

Evans: And chron­ic pain is a biopsy­choso­cial con­di­tion, which means that it’s life, it’s mind and it’s living.

Treede: Yep.

Evans: We are all those things.

Treede: This maybe brings us to the point of qual­i­ty of life. When we talk about qual­i­ty of life in the con­text of chron­ic pain, we think of aspects of every­day life, such as activ­i­ties, fam­i­ly life and so on. How­ev­er, when you talk about the qual­i­ty of life in gen­er­al terms, then the absence of pain is one of the major con­stituents of qual­i­ty of life. So if you talk, let’s say, about endocrinol­o­gy, periph­er­al neu­ropathies, the absence of pain is a major issue for qual­i­ty of life and actu­al­ly, it’s even a pre­dic­tor of mor­tal­i­ty. The same can prob­a­bly be said about car­dio­vas­cu­lar dis­ease, def­i­nite­ly for can­cers, so if the can­cer is con­trolled and there is no pain, the qual­i­ty of life is bet­ter, than if the can­cer is con­trolled and there is pain.

So clear­ly pain or absence of pain is a major fac­tor of qual­i­ty of life, but it’s not the only one and this is in the psy­cho and social domain of the biopsy­choso­cial mod­el. It sounds very com­pli­cat­ed but day-to-day liv­ing activ­i­ties play a major role, the well­be­ing from the patient’s per­spec­tive – not some bio­log­i­cal para­me­ter, blood count or imag­ing find­ing – but real­ly the well­be­ing of the patient plays a role. And here pain is defined as a sub­jec­tive feel­ing, so pain is when it hurts.

The one thing we haven’t approached is the plas­tic­i­tiy of the sys­tem and we tend to think that the sen­so­ry sys­tem has a cer­tain set­ting and that it stays like the set­ting of your micro­phone, set to a cer­tain sen­si­tiv­i­ty. Now this is not true for the noci­cep­tive sys­tem, this real­ly becomes much more sen­si­tive, when­ev­er some­thing impor­tant hap­pens it imme­di­ate­ly becomes much more sen­si­tive. And then it becomes bor­ing then it becomes less sen­si­tive again and so it’s high­ly plas­tic and this is not real­ly appre­ci­at­ed very much.

The sen­si­tiv­i­ty of the noci­cep­tive sys­tem is dif­fer­ent between peo­ple, but in the same per­son, it is also very dif­fer­ent over time. The sim­plest thing, is if you con­sid­er you have an injury, it could be a minor injury, so you don’t even see a doc­tor. You have a cut, or a burn, or some kind of injury doing gar­den­ing work this time of the year, or what-have-not, then the injured body part becomes more sen­si­tive to poten­tial­ly dam­ag­ing stimuli.

So many things that would­n’t nor­mal­ly hurt, rel­a­tive­ly mild touch or sharp objects are more painful. And you may also notice that you are more sen­si­tive to heat­ing, so that heat­ing is actu­al­ly painful. And that’s a pro­tec­tive mech­a­nism. So, the warn­ing sys­tem of the body enhances its sen­si­tiv­i­ty, its gain, when­ev­er there has been an injury. It does it at all lev­els, even at the very periph­er­al nerve end­ings. Here we know some of the mech­a­nisms plus cer­tain chan­nels and so on, but also in the pro­cess­ing of the sig­nals of the cen­tral ner­vous sys­tem. We know most detailed infor­ma­tion about the spinal cord, so when the spinal cord has received a strong warn­ing sig­nal, then it becomes more sen­si­tive to the next sig­nals, as if it were lis­ten­ing to see if there were more to come and that would be the cen­tral sen­si­ti­za­tion and the oth­er would be the periph­er­al sensitization.

Evans: So it’s learnt, for want of a bet­ter word, what hap­pened last time and works to avoid that same thing hap­pen­ing again?

Treede: It is a learn­ing mech­a­nism, absolute­ly. Many peo­ple use the word pain mem­o­ry and it’s not quite clear what they mean. If you look at mem­o­ry research, there are lots of dif­fer­ent mem­o­ry and the sim­plest type of mem­o­ry is basi­cal­ly non-asso­cia­tive, just by repeat­ing stim­uli. There are two things that could hap­pen, one thing is, the response could becomes less, that’s called ‘habit­u­a­tion’, when the stim­u­lus is bor­ing or unim­por­tant, usu­al­ly when it’s weak, or sen­si­ti­za­tion could hap­pen when the stim­u­lus is strong or impor­tant or threatening.

This is exact­ly what the noci­cep­tive sys­tem does, so when there is a real injury, that is impor­tant, so by the real injury it becomes more sen­si­tive in the periph­ery, in the cen­tral ner­vous sys­tem. But this is a mem­o­ry process that does­n’t last very long. It is long term mem­o­ry but in the sense of about one day. I usu­al­ly com­pare this with study­ing for an exam, where you mem­o­rize things for the next day and then you start for­get­ting. The same thing hap­pens with our warn­ing sys­tem, if the injury heals, then we for­get about it, but if we have repet­i­tive injuries, then we enforce the learn­ing and maybe we can have a longer last­ing mem­o­ry. So, the term ‘mem­o­ries’ is absolute­ly appropriate.

Evans: So what hap­pens when you say nor­mal­ly that mem­o­ry will go with­in a day what hap­pens if it doesn’t?

Treede: That’s real­ly the big ques­tion. An inter­est­ing thing about chron­ic pain is that many peo­ple can have had the same injury and don’t devel­op chron­ic pain. So the idea is there must be indi­vid­ual dif­fer­ences to sus­cep­ti­bil­i­ty to devel­op chron­ic pain for some kinds of injury. I men­tioned after injury the pain goes away one or two days. It’s also true for major surg­eries and most peo­ple can be dis­charged very quick­ly and they don’t have pain.

How­ev­er, some 10 or 20 per cent still have pain and the big ques­tion is, is this due to a delay in the heal­ing process? Maybe in some cas­es. But in some cas­es this may real­ly reflect a dif­fer­ent a pri­ori set­ting of the warn­ing sys­tem. In these patients, the warn­ing sys­tem has a longer mem­o­ry than in oth­er peo­ple. The indi­vid­ual dif­fer­ences, we can actu­al­ly mea­sure those and the idea is that maybe an impor­tant con­trib­u­tor to chron­ic pain is this indi­vid­ual sus­cep­ti­bil­i­ty to hav­ing longer last­ing pain mem­o­ry than the aver­age population.

Evans: That’s Pro­fes­sor Rolf-Detlef Treede of Hei­del­berg University.

I’ll just remind you of my usu­al words of cau­tion, that whilst we believe the infor­ma­tion and opin­ions on Air­ing Pain are accu­rate and sound, based on the best judge­ments avail­able, you should always con­tact your pro­fes­sion­al on any mat­ter con­nect­ed with your health and well­be­ing. He or she is the only per­son who knows you, your cir­cum­stances and there­fore knows the appro­pri­ate action to take on your behalf.

Don’t for­get you can down­load all the pre­vi­ous edi­tions of Air­ing Pain or obtain CD copies, direct from Pain Con­cern. If you’d like to put a ques­tion to Pain Con­cern’s pan­el of experts or just make a com­ment about these pro­grammes, then please do so via our blog, mes­sage board, email, Face­book and Twit­ter or pen and paper, all the con­tact details are on our web­site that’s

Now I’ll end this edi­tion of Air­ing Pain with what may or may not be that stu­pid ques­tion I referred to ear­li­er, I’ll let you be the judge. Can pain be measured?

Treede: Usu­al­ly I say there are no stu­pid ques­tions, this is my one excep­tion. This is accord­ing to the def­i­n­i­tion — pain is what a per­son feels. It’s defined as an unpleas­ant emo­tion­al and sen­so­ry per­cep­tion that is relat­ed to injury but may also be unre­lat­ed to injury, it is just the sub­jec­tive, first per­son expe­ri­ence that is pain.

There is a term for the oth­er thing, the thing we can mea­sure objec­tive­ly, that’s ‘noci­cep­tion’. It goes back to a famous British reflex phys­i­ol­o­gist, Sheri­dan, who noticed that some reflex­es are elicit­ed by poten­tial­ly dam­ag­ing stim­uli. No mat­ter which modal­i­ty they come from, they elic­it defen­sive reflex­es. This led neu­ro­bi­ol­o­gists to dis­cov­er the noci­cep­tive sys­tem that sens­es either dam­age or impend­ing dam­age – it’s a warn­ing system.

And activ­i­ties of this warn­ing sys­tem can be mea­sured, of course. You can start in the periph­ery – even in peo­ple – you can mea­sure the periph­er­al nerve activ­i­ty. You can mea­sure reflex­es, also in peo­ple, spinal reflex­es, you can mea­sure car­dio­vas­cu­lar reflex­es and you can mea­sure brain activ­i­ty with elec­tro­phys­i­o­log­i­cal means, like EEG [elec­troen­cephalo­gram] or you can do PET [positron emis­sion tomog­ra­phy] imag­ing. But this is real­ly look­ing at sig­nal pro­cess­ing in the noci­cep­tive sys­tem and whether or not this activ­i­ty leads to pain, depends on the inter­nal state of the brain and many things. So real­ly, pain or not is the sub­jec­tive report, that’s the definition.

Evans: I mean, that is inter­est­ing, as we’re con­duct­ing this infor­ma­tion in a dark, pit of a room, with no light and with actu­al­ly very, very unpleas­ant­ly loud air-con­di­tion­ing. If we were out­side in the sun­shine, my pain score and per­haps your pain score would be com­plete­ly different.

Treede: Well, absolute­ly, one of the most pow­er­ful way to mod­u­late pain is atten­tion, the effect size is pret­ty much the same as that of strong anal­gesic med­ica­tions. You could say if you have a headache, so if you do men­tal arith­metic, you could say you get as much pain relief as a pain killer. Now when you have a headache, you prob­a­bly don’t want to do men­tal arith­metic, so it does­n’t have a prac­ti­cal con­se­quence. But the effect of atten­tion con­trol is extreme­ly powerful.

Evans: This is where talk­ing ther­a­pies cog­ni­tive behav­iour­al ther­a­py, visu­al­i­sa­tion, med­i­ta­tion all play their part in our pain.

Treede: Yes, absolute­ly, so the cog­ni­tive part of cog­ni­tive behav­iour­al ther­a­py is rel­a­tive­ly explic­it about these things and the behav­iour­al part is less explic­it, where we just use learn­ing mech­a­nisms of the ner­vous sys­tem to enhance some behav­iours over oth­er behaviours.


  • Ana Valdes, Asso­ciate Pro­fes­sor and Read­er, Fac­ul­ty of Med­i­cine and Health Sci­ences, Uni­ver­si­ty of Nottingham
  • Rolf-Detlef Treede, Pro­fes­sor of Neu­ro­phys­i­ol­o­gy, Hei­del­berg Uni­ver­si­ty, Germany.


Comments are closed.