okay it’s a pleasure to be here on this blustery cold Mayday in in after such a difficult winter I’d like to thank the organizers for the invitation to speak to you today and thank you for coming I find I think it’s an important part of what I do as a professor at York to be able to feed back to you the kinds of research and things that we do when I say we I mean myself and my students and i’ll be presenting some of the work that my students have done as well and I think it’s especially important for you to see how your hard-earned tax dollars go towards supporting me my students are research and you will be the ultimate deciders as to whether you feel it’s worth while I hope you feel that it is okay so as James said I’m going to be speaking on chronic pain after surgery epidemiology risk factors and something called preventive analgesia today’s talk is good news bad news good news bad news story and actually it’s mostly a bad news story but I’m going to get the good news out of the way okay but good very quickly and the rest will be the bad news so the good news is that the vast majority of people who undergo major surgery recover uneventfully so within weeks or months after the surgery they heal they return to their everyday activities be that student worker whatever and usually with an increased quality of life better than what they had before so that is the good news okay the bad news is that I believe we have an epidemic of chronic post-surgical pain I mean we clearly have an epidemic of chronic pain but I hope to convince you today by my presentation and I have a lot of slides with data and numbers and things like that we have an epidemic of chronic post-surgical pain we’re learning more and more about the factors the risk factors that predict the development of chronic post-surgical pain and its maintenance but at present were a long way from being able to predict who will go on to develop pain and who’s going to recover uneventfully and as you’ll see from what I present one of the most robust predictors or risk factors is pain itself so you’ll see that the existence of pain before surgery predicts the development of long-term pain after surgery and that the intensity of acute pain after surgery also predicts it but the question as you’ll see is what is it about pain that’s predictive and I won’t say anything more about that now what I will say is that as with most chronic intractable pain problems chronic post-surgical pain when it’s severe has a way of lodging itself into the core of the person and from there having all sorts of negative downstream effects so chronic post-surgical pain ruins lives it ruins families it leads to separation to divorce it leads to job loss that leads to isolation people stopped coming around after the first month or so it leads to worry anxiety about what does the pain mean about how am I going to be able to support myself and my family it leads to depression and at times even to suicide and so this is a slide by the mexican painter Frida Kahlo and there was a Hollywood movie I don’t know eight or so years ago about her life which I should tell you really was Hollywood it

exaggerated the good and downplayed the pain and she had had a number of very painful accidents in her life one of them ultimately that led to an amputation of below knee amputation and this is a picture from her diary and for those of you who don’t speak Spanish and I don’t but I do know the translation what she’s written here is feet what do I need them for if I have a wings to fly and here’s what she said she said they amputated my leg six months ago they’ve given me centuries of torture and at moments I almost lost my reason I keep on wanting to kill myself never in my life have I suffered more I will wait a little while and then so that’s in February of 54 and in July her last entry in her diary is I hope the exit is joyful and I hope never to come back Frida and her friends who were with her that evening were convinced that she had deliberately taken an overdose of the morphine that had been provided for her for pain relief because of the pain she had been in so in the time that remains here’s what I would like to to cover a bit on the epidemiology or the course of chronic post-surgical pain in adults and in children and so you should note that it’s bad enough to have chronic pain as a grown-up but it’s a tragedy when children develop pain after surgery and when it doesn’t go away and so we’ve done a bit of research on that and i’ll be presenting some of that to youtube i want to define what a risk factor and a protective factor is and then present the data that we have in the literature that suggests or that that identifies what these risk and protective factors are and there I’ve grouped them into this category of these categories I won’t be going over all of them because I don’t have all the time but there are surgical factors that predispose one to develop pain in the long-term more than if that factor is present more than other people who don’t have that factor there’s psychological social environmental factors cognitive neuropsychological factors individual of different factors and anesthetic and analgesic factors and of all of those it’s the last one that is a protective factor that is there are things that anesthesiologists can do during surgery and before to minimize the risk of developing long-term pain certainly to minimize the risk of developing acute pain intense acute pain and I should say that there is a debate in the literature so my point of view is biased in favor of there are things that we can do and I have interpreted the evidence as suggesting there are beneficial things but not everybody is on the same page so you need to know that and then all conclude with a few ending comments okay so as with most phenomena it’s good to have a mutually understood agreement about what it is we’re talking about and the same is true with chronic post-surgical pain and there is a now a four-point definition of chronic post-surgical pain and you’ll see that there it’s fairly straightforward although two of the points are more important than the others and i should say this slide here depicts the only type of surgery that won’t lead to the only type of disc surgery that won’t lead to chronic post-surgical pain it’s probably the most that statement I will be no more confident about saying anything else than that okay so what is it well the definition obviously pain must have developed after a surgical procedure it must be of at least two months duration which I think and others to think that might be a bit too short of course it also depends on the type of surgery some surgeries heal much more

quickly like a hernia repair as opposed to an amputation of a limb so that’s kind of debatable but these last two points are important because they partly explain the wide range you’ll see in the estimates of how frequently chronic post-surgical pain is said to occur because there’s a lot of variability and it’s important at least in the research field as well as clinically to rule out other causes of the pain so if one has had surgery for cancer and pain is present a year after one needs to rule out the possibility that the cancer has recurred if that’s the case as with chronic infections then that isn’t really post-surgical pain that’s pain that’s arising from a new cause and in the same vein one needs to rule out the possibility that someone who has had pain before surgery and who has chronic post-surgical pain that one makes sure that the pain they have in the long term isn’t just a continuation of pain they had before in terms of studying this phenomenon of chronic post-surgical pain this slide shows how complicated it can be because if one takes a life span approach for example you can look at surgery in infancy and then the subsequent development of pain later in infancy and childhood and in adolescence in adulthood and in old age and likewise you can study surgery and children and follow them and this is really most of where the literature is it’s looked at surgery and adults and followed them mostly for one year which most people would admit is not even a long time occasionally there are studies that have looked at pain after five years those are very very rare but we know that ain persists for many many years and in the case of limb amputation it’s not uncommon to continue to have what’s called phantom limb pain for 20 or 30 years so i’ll be presenting some of the work we’ve done in adults and some we’ve done in children and adolescents so my introductory comments suggested not even suggested stated we have an epidemic we’ve got a big problem so let’s take a look at how big a problem it is and I’m going to do this from two approaches I’m going to look at a study that evaluated intense pain immediately after the surgery and then followed people for a year and then take the other perspective which is to look at people who have already have chronic pain and see what the breakdown is for the reasons for the pain so the first study was one done by Chris Hayes in Australia and they studied about 5,000 people seen by an acute pain service while they were in hospital and they evaluated them over a two-year period they diagnosed the incidence of what was called acute neuropathic pain at one to three percent so one to three percent of the patients that they saw immediately after surgery had this mural pathak pain and the hallmark feature of the neuropathic pain early on is a really high intensity so this VA s equals 9 out of 10 vs is a visual analog scale think of as a ten-centimeter scale where you have no pain at one end most intense pain on the other and you just mark where your pain is along there the average pain of these patients who developed acute neuropathic pain was a 9 out of 10 so that is really intense so they followed them up six months and 12 months later you can see at six months seventy-eight percent continued to have pain and at one year fifty-six percent say so half of them continue to have pain one year later so the conservative estimate then for the 12-month incidence is that if we take fifty six percent of the one to three percent and take 56 as 50 so that’s one half of one percent to 1.5 percent of people will develop chronic post-surgical pain in a year later and

this is conservative now you might not think that that’s a lot a half of a percent but if you look at the literature on how many people undergo surgery every year and I have data from the United States we don’t have this kind of data I couldn’t find it Canada but this is for ninth for 2005 a national hospital discharge survey in the United States more than 26 million surgical procedures were performed on patients in a hospital so if we take 0.5 to one point five percent of 26 million that is 30,000 two not three hundred and 130,000 to three hundred ninety thousand cases of chronic post-surgical pain this year but because we’re talking about incidents which is a number of new cases so that’s a hundred and thirty-two 390,000 patients this year attitude 130 to 330 390 last year added to the year before and the year before that’s that’s that’s huge and it’s conservative I believe if you look at children the data show that six million surgical procedures were performed so if we do the same a half of one percent to 1.5 of six million is 30,000 to 90,000 new cases of chronic pain and children okay so knowing now that there’s a lot of people out there with chronic the surgical pain this won’t come as a surprise to you this is another large-scale study this done by ian cromby in northern England and Scotland and they also studied about 5,000 patients this was a retrospective survey of as I say 5,000 patients so from 10 chronic pain centers so these are people who already have chronic pain and are being referred to a specialized Pain Center for treatment and what you can see and I think not surprisingly given the data I presented just before almost a quarter of the patients who are referred to these pain centers suffer from chronic blow surgical pain and then the rest is not surprising given that in order to get seen by a specialized Pain Center you need to have had it for a while and it needs to be intense sixty percent had it for at least two years it was of moderate your intensity in three quarters and again not surprisingly associated with a significant disability or the by disability is meant how much the pain interferes with everyday activities and this is a smaller study done by one of my former graduate students Andrea Martin where we followed just over a hundred and forty kids who had been seen by a pediatric chronic pain clinic in Toronto and we contacted them three years after they had been treated and discharged and sixty-two percent reported their pain persisted the mean intensity this is a different scale but it’s still a zero to ten and eleven point scale the average intensity of a six point one out of ten and almost seventeen percent had been referred because they had had surgery and the pain had arisen because of this and this is paying that now is persisting this slide here shows you what’s called an inside-out plot of the incidents on the left and the prevalence on the right of a variety of different surgeries and the incidence prevalence of chronic post-surgical pain that arises after them so you can see that the 0.5 to 1.5% isn’t even there I mean it were hot we’re talking about a greater incidence and prevalence and even for surgeries like a hernia repair where’s hernia repair here which is a not a major surgery it’s a minor surgery but we have 22 or so percent of patients after one year reporting the chronic pain referred to the penguin ille area i mentioned phantom limb pain % one to two years later there’s work by a colleague of mine twenty years later

people still having phantom limb pain after an amputation and even after a post c-section one year later about seven percent this slide shows the same thing but for children there isn’t as much data but it’s equally alarming and this is the study that we conducted or one of my graduate students did and here we have one year after major orthopaedic surgery about twenty-two percent of kids reporting chronic post-surgical pain of moderate to severe intensity that’s like a four or more on that 0 to 10 scale so I want to spend a bit of time on on risk on understanding risk and by understanding risk i don’t mean the board game of global domination nor do i mean try to understand why this fellow would do what he does this is alan robear who’s the real spider-man the human spider man who climbs the world’s tallest buildings without any safety gear and this is him reaching the top of the aspire building in Qatar in 2012 which is 300 meters and he did in 73 minutes and actually from what I gather this is an easy climb because you can see there’s that middle grid I mean easy i don’t mean easy for me but easy for him I mean he has climbed buildings that are just solid concrete anyhow I am not even though I am a psychologist I am NOT talking about understanding this I’m talking about understanding the terms risk and protective factors and what they mean and how they’re defined so they’re really two important parts to understanding what a risk factor is even though there’s 44 point definition here so it needs to be a risk factor needs to be something that you can measure every person and importantly it has to be measured before the outcome of interest so if we’re talking about what are the risk factors for chronic post-surgical pain and I say pain is a risk factor we need to measure pain before surgery or after surgery but certainly before the chronic pain develops right and then this risk factor can be used to divide the entire sample into people who are at high risk and those who are at low risk and also another important point is that risk factors are then used to say well what is the probability how much greater how much more likely are you to develop the outcome if you’re in the high risk versus the low risk group and risk factors are to be distinguished from these other things which are called correlated factors so if you don’t measure it before the outcome if you for example just decide I’m going to call up a thousand people like they did in that retrospective study and i’m going to ask all of them who has chronic post-surgical pain and then say by the way did you have pain before surgery yes or no you’re measuring whether they had pain before surgery after so it isn’t a risk factor it’s a correlated factor and in that instance it might even be in consequence of well in this case you can’t do but it can be a symptom so we need to distinguish correlated factors from risk factors and then there are correlated risk factors and that those are risk factors that precede the outcome but if you try to change them or modify them like for example let’s decrease pain and see if that does something in the long term if modifying the risk factor has no effect then it’s called a correlated risk factor if modifying a risk factor removing pain before surgery for example if that changes the risk of developing chronic post-surgical pain then you have what’s called a causal risk factor and this is what we are looking for not only us but anyone who does this kind of research is looking for causal modifiable risk factors so some risk factors are correlated so no matter how much you modify them it has no effect on the outcome we’re not that

interested in those so here are the various categories of risk factors and as I mentioned before if you think of the term protective factor it’s the same thing as a risk factor but it’s something that’s good right a protective factor protects against the development of of the outcome and if the outcome is pain then that’s a good thing so I’m going to just go through some of these some of the surgical risk factors the duration of surgery so the longer the surgery the more likely a person is to develop pain in the long term this you want to take note of you have a 13-percent increased risk of developing chronic post-surgical pain if you have surgery in a low volume versus a high volume surgical unit why might that be there in a hurry maybe an experience right the more the more patients going through the more experience the less likely but this is only one study you’re at greater risk this is for hernia repair for chronic pain growing pain if you have what’s called an open approach versus a laparoscopic approach so openness where they this is how surgeries were done traditionally they make an incision and they take out or fix whatever they need to do many Sonja back and laparoscopic surgery involves very small incisions and then doing the surgery through some mechanical means where you don’t have to make a huge incision something called Perry coastal versus intercostal stitches for thoracic surgery mostly for lung cancer and I think all of these point to the main culprit the main culprit is nerve damage or nerve lesion during surgery either in it in advert intentalo as in the case of when a nerve might get nicked during surgery or a nerve might get tied up in a suture or intentional and unavoidable in the case of limb amputation where major nerve trunks are ligated tight and then cut so there are times where you can’t help it and there are times where you can and so in terms of what we know definitely intraoperative nerve damage is a risk factor for chronic flow surgical pain is it modifiable well in some instances it is for example if the surgeon cuts a nerve to get a better view of the operative field that’s avoidable and that probably shouldn’t be done in other cases it isn’t and is it causal yes most of my colleagues would agree in fact most of the animal models that basic science researchers have for studying and try to understand and improve pain in humans they use animal models involve damage to nerves okay psychological and emotional factors well fear of the long-term consequences of surgery so if you’re worried about surgery beforehand your risk is increased for a long-term pain if you’re depressed before surgery your risk is increased if you engage in something called pain catastrophizing which is worrying a lot above the pain feeling helpless in the face of pain your risk is increased and then there’s other factors that we measure not necessarily before surgery but at points in time after surgery that also predict the development of chronic post-surgical pain and pain disability is one something we’ve called sensitivity to pain traumatization some people are really afraid of pain they get traumatized by it and this construct predicts the development of paying a year later and I won’t talk about this right now so again the only factor the most clear-cut finding is this construct called pain catastrophizing this worrying about pain being feeling helpless in the face of pain is a risk factor we know it’s modifiable because through psychological techniques such as cognitive behavior therapy and others we can reduce people’s level of worry and

concern the question is will reducing that change the outcome and we don’t know that yet though I do know a colleague of mine at McGill is doing a study to look at this this is the most robust finding in the field but ones highlighted in in bold-faced font all have to do with pain and I said this at the beginning pain predicts pain there is no there’s no other factor that is more predictive of pain than pain itself so the intensity of preoperative pain the presence of preoperative pain predicts the development of long-term pain the intensity of acute pain predicts the development of long-term pain a high consumption of analgesic of analgesics after surgery which is a proxy for intense pain is also predictive as is pain and other body parts the younger age female sex is not it hasn’t really panned out there’s probably an equal number of studies that show that that isn’t the case but the biggest factor is paying itself so let me give you an example of excuse me of what we mean by pain predicting pain yes it’s modifiable but we don’t know if it’s causal this is a very small scale study we did several years ago where we interviewed and assess patients immediately after thoracic surgery and then follow them for 18 months so we contacted them 18 months after and asked them did an interview about whether they have developed chronic post-surgical pain and if they had how intense it was so almost half were pain free and the other half reported pain on a daily or weekly basis a dull aching or burning pain which is characteristic of neuropathic pain and it had a mean intensity on that 0 to 10 scale of a 3.3 so what we then did was after classifying them as pain free or having pain we went back to the records that we had collected when they had surgery and looked at what their pain scores were immediately after so here you can see on the y-axis which is the up and down one this is pain 0 to 10 at rest just lying down as comfortably as one could be after the surgery and what you can see is that as early as six hours after surgery and going up to 24 the people who reported themselves to be pain-free 18 months later had significantly lower pain than the ones who went on to develop pain so as early as six hours later one can predict at least based on these who is more likely develop long-term pain and likewise with what we call pain on movement in this case it’s because the incision is done here taking a deep breath stretches the stitches and causes pain we don’t want to cause pain but it’s good to move about after surgery so pain on movement is also predictive of long-term pain so the people who had a lot of acute pain after taking that deep breath were the ones who went on to develop long-term pain and this was in the face of no differences in analgesic consumption though so this is milligrams of morphine that the two groups took and they took basically the same amount which itself is a mystery actually and this study we just published last year done by another grad student Gabrielle pashe of mine who’s almost done and ready to move on looking at a very similar thing but in children and these were children who had undergone major orthopedic surgery mostly for spinal stenosis so we did the same thing we saw them right after surgery we followed them up two weeks six months and a year later at the one year mark we classified them into a high pain group and a low or low pain group and then we went back and looked at what were their pain scores like early on so here’s what we found we have two graphs pain intensity how strong how intense what is the magnitude of the pain and what we call pain unpleasantness how much does it bother you how unpleasant

is it and you can see the graphs are pretty much the same what you can see is that these closed circle dotted lines are the patients who at one year had no or mild pain and the open circles are the patients who had moderate to severe pain right so what you can see is that the two trajectories this one going down and this one kind of going up or staying constant the main difference occurs at about two weeks after surgery and so what we found was that kids who had a pain score of three or more on that scale were two and a half to three times more likely to go on to develop a moderate to severe pain one year six months to one year later then the kids whose pain was less than three of two weeks so here we have it again paying predicts pain and i must say a lot of my colleagues are not a lot but you know some jumped on these findings and said okay well now we have the answer right paying predicts pain all we have to do is get rid of pain for get rid of pain before we’re not going to have any pain but that’s assuming that pain is a causal risk factor and we don’t know if it is it might be and i’m going to show you more about this so this is actually what we teach our you know psych 101 students the difference between correlation and causation just because two things occur together doesn’t mean that one is causing the other and so this is the million-dollar question what is it about pain that predicts pain so if you think about other things in your life that predict itself you’ll see why it might not be so clear cut so a good example is height long babies turn into tall kids turn into tall grown-ups right no one would say that height causes like height as a baby causes you to be at all adult right there just correlated why well must your jeans or school performance doing really well in grade school predicts doing well in high school predicts doing well in university and no one would say that doing well in grade school causes you to do well and so likewise with pain but for some reason it’s a bit harder to tease those two apart but we’re going to do it as best as we can so these I’m not going to go through them all that these are some of the risk potential risk factors for why pain predicts pain some of the explanations they’re not mute their non a mutually exclusive meaning that more than one can be happening at one at the same time some of them are causal some of them are correlated and some of them are modifiable and others are not so I’m just going to go through maybe one or two but if we take an example of nerve damage that I said is probably a culprit so if there is nerve damage during surgery that causes immediate pain after surgery and then something called ectopic activity where the nerve starts to fire from a site that it doesn’t usually fire and that gives rise to pain so in this case we have a causal risk factor which is at least at present not modifiable by any of the known drugs that we have at least known drugs that can be given clinically central sensitization this is a one of our buzz words in the field when a nerve is injured it emits a high frequency burst of activity that can be recorded and associated with that high frequency burst of activity is a release of neurotransmitters called excitatory amino acids and neuro peptides these are released from the central ends of the nerve that then leads to a sensitization

an increase in the response properties of the neurons that it has just released its neurotransmitters onto and this central sensitization is accompanied by feelings perceptions of increased pain so this is causal and it is modifiable so if it’s maintained by peripheral input maybe we can block the peripheral input genetic factors well that would be causal and that would not be modifiable at least at present so let me give you an example of let me just go back here sorry another one is structural changes in the central nervous system kicking things we’ve called pain memories that occur in amputees or others have called the centralization of pain where pain becomes autonomous it doesn’t require the periphery to drive it anymore and these pain memories here’s an example if you ever have time I would suggest you see a website by Alexa right this is her she’s a photographer and an artist who teamed up with a neuroscientist by the name of Peter Halligan from the UK and they together interviewed a number of people who had undergone a putative and you can see what she did here is she took a picture of the intact limb in this case her right hand and she flipped it digitally and then based on her interview and the descriptions that each person had given her about what her phantom limb felt like she made the phantom look exactly as it feels so this is a phantom limb that is it isn’t her real limb her arm has been amputated right here but this is what she feels this is the phantom limb right you all have you all heard of phantom limbs before yeah okay so you you’ll see this is a good example of this pain memory because you can see well here here’s what she said she said at the time of the accident she was in a car accident and the car flipped over and her arm was outside of the car at the time of the accident I was aware that my engagement ring cut into my finger and that is still there so part of her phantom limb involves feeling an engagement ring which you can see here she feels it and this is continuing to cause her distress so this is an example of what we call a pain memory it isn’t a memory as in the memory I can remember although it is partly that as well it’s also not only can I remember the pain that I felt but I also can feel the physical sensory sensations that I had at the time so this is the million-dollar question why is it important to distinguish between the causal risk factor model in the correlated risk factor model the causal risk factor model says that for example pre amputation pain leads to phantom limb pain right by changing the central nervous system so that it stamps in or etches in an existing impression and that that comes back literally to haunt the person after amputation versus the correlated risk factor model which says that for example a psychological predisposition is what is responsible at both time so a good example is anxiety if you tend to be highly anxious at one time in your life you may be highly anxious at another and one would again never say anxiety at time one is causing anxiety at time two okay so why is it important so the next sequence of slides will give you an idea so if the intensity of preoperative pain causes chronic pain as in the case I just gave you of a pain memory or if the intensity of acute post-operative pain say in the days after surgery is also causally

responsible for developing chronic pain either through this injury barrage that I didn’t really talk about and the inflammatory response then a logical hypothesis is that if you perform an anesthetic block like for example what the dentist does or what an epidural is a good example of that if you perform an anesthetic blog sufficiently in advance of surgery and for example if you continue it throughout the surgical post-operative stay so that you block any pain then you should render the patient or the person pain-free right because if there is no pain to persist then there can be no pain in the long term it’s like what in in psychology we talk about declarative memory so a good example is the best way to forget is never to have learned in the first place yeah so this is kind of the same idea let’s block pain and the transmission of it before surgery and throw out and see what happens and if it’s causally related and pain is responsible this should help but what if that isn’t the case what if we have what’s called a correlated risk factor model where the intensity of acute pain is associated with the development of chronic pain but it doesn’t cause it they just both occur together and that each one of those is themselves caused by some higher order factors may be genetics nerve injury catastrophizing that are the causal mechanisms so in that case no amount of blocking of the pain is going to have any effect on it because it isn’t causing it right and as with most things the world is much much more complicated than simple models and I think we have a dual factor model where where some aspects of krav acute and preoperative pain are causative and others are just associative and our task is to try to figure out which is which so this is and I don’t expect you to be able to read it I just want you to admire the artwork I’ll tell you it took me like a long time to do this but what it reflects is the risk and protective factors that the known risk and protective factors that are involved in pain becoming chronic and it shows these risk factors in the preoperative phase the intra-operative phase and the acute and long-term post-operative pain the factors that predict pain and pain disability and you can see their biological psychosocial the surgical factors so it’s a complicated story and now i’m going to highlight just one circuit of that model and this is the circuit of what’s called preemptive or preventive analgesia this is where I said there are things that might be able to be done by anesthesiologists that can help in minimizing the intensity or the incidents so let’s look at a few of the study so here you can see these are studies that have shown that giving for example an epidural which I think are you all familiar with epidural it’s like a catheter is inserted into the epidural space many women have epidurals for childbirth for labor pain and a local anesthetic or an opioid a morphing like substance is an opioid and a local anesthetic is like lidocaine with the dentist used to freeze you those agents are injected into the epidural space and they block transmission of nerve impulses at the level of the spinal cord so if you have a really really effective epidural it will tremendously cut down on the pain or the pain impulses that are traveling up to the spinal cord so using perioperative epidurals meaning giving it a for surgery and continuing it throughout has been shown to reduce the incidence and intensity of chronic post-surgical pain likewise something called multimodal analgesia which is administering different agents by different routes so come combining the

actions of different agents like opioids local anesthetics nonsteroidal anti inflammatories things called alpha 2 delta ligands gabapentin and pregabalin has been shown to be effective as well as have these other studies so i’m just about running out of time because i want to leave some time for comments and i’m going to just if you’re interested we published a paper in 2011 in anesthesia and analgesia called preventive analgesia quo vadimus where are we going and it’s not I mean there is a lot of science in it but it is definitely readable and it outlines the work that’s been done over the past 20 or so years so let me finish by getting you telling you the results of a study we can read out a few years ago testing this idea of pre-emptive or preventive analgesia and this was in women who were undergoing mostly while it’s abdominal gynecological surgery by laparotomy so it would be mostly abdominal hysterectomies and here’s the how the study went people were recruited informed about the study assessed before and then randomly assigned in what’s called a double blinded manner so neither we the researchers know them the patients knew what group they were going to be assigned to though they didn’t know what the three groups were they just didn’t know what they were going to get and there were three groups Group one received through the epidural route a two syringes one syringe contained fentanyl which is a very potent fast-acting opioid like morphine and the second one contained lidocaine which is like the same agent that the dentist uses to freeze you Group two received two syringes containing epidural saline so this is a control over placebo condition and group three I won’t go into it now but they received what we called a sham epidural so an epidural was not inserted but the anesthesiologist went through all the motions of doing it they didn’t actually insert the catheter everybody had general anesthesia as is the standard of care and a standard practice for this type of surgery so these groups are actually this group is actually getting more than the standard and then i would say about 40 minutes into the surgery groups one in group two were crossed over so Group one that received the active agent before now receives two syringes of epidural saline and group two that received the saline now receives the active ingredients the fentanyl and lidocaine and this group receives two more in shins into nowhere and then surgery ends and we follow them for several days and then for three weeks and six months after so just to review the only difference between group 1 and group 2 is the timing of administration of the active agents relative to incision right group 1 is blocked if you will at the time the surgeon makes the incision the cut is made the nerves actually do conduct their electrical signal but they are stopped at the level of the spinal cord because of the epidural so nothing not much gets in in terms of that injury to start that central sensitization thing I talked about Group two and three on the other hand well there’s nothing in those syringes and general anaesthesia doesn’t block this injury discharge from being transmitted throughout than your axis and so they receive the full brunt of the effects of the surgical incision that release of excitatory amino acids that central sensitization so it’s sort of stopped in this group if you will after but they’ve received 45 minutes of that injury discharge so everybody’s clear on the design so what do we expect well we expect this group to have less pain than this group certainly and possibly even this group so let’s see what we found well in contrast to what I just said pain scores were not different between the three groups are among the three groups but what I forgot to tell you was that everybody received what’s called a PCA pump a patient-controlled analgesia

pump where they’re hooked up to a pump that is that dispenses morphine every time you press a button subject to a lockout and safety factors you get a bolus dose of morphine so you can self administer it and I think that is why we had no differences in pain because people are using the morphine pump to titrate their pain and you’ll see the results but if we look at in the movement pain we had a significant a slight but significant difference at 24 hours between the patients who got the pre-operative epidural those are these here they have significantly less pain than the control shanna epidural control loop and the thing to note that this is at 24 hours after surgery which is at a point in time when the clinical duration of action of the of the fentanyl and lidocaine have long warned off so this is no longer an analgesic effect this has to do with blocking the central sensitization that arises in this group here we also looked at pressure sensitivity near the wound by poking at it basically and this represents the log milligrams of pressure of force and here too you can see that the threshold is much lower or ciggy I don’t know if it’s much lower but it is statistically significantly lower lower meaning you feel more pain higher meaning you have you can take more pressure again at 24 hours favoring the pre incision over the control group with the post group is sort of intermediate never never different from either group and here’s where the main effect is as I mentioned before which is in the morphine consumption so this shows an hour-by-hour plot of how much morphine cumulatively each of the three groups took over time and you can see that if we just go to the 48-hour mark which is when they were stopped on the PCA pump the patients who had the pre a preoperative a pre incisional epidural had lower morphine consumption by twenty-two percent compared to the Sham epidural group and again we have this post incisional group is intermediate between the two so this clearly says doing something before surgery in terms of administering local anesthetics and and and opioids through the epidural root has a beneficial effect that can be observed 48 hours up to 48 hours after surgery so then we follow them up three weeks later and six months after that and i’m going to show you only the three week data because there was no effect at all at six months and a little only a little effect that had persisted at three weeks and so these are the variables that we measured follow-up time didn’t differ between or among the groups which is what we expect the incidence of pain is by and large the same worst pain since they were discharged just about the same another pain rating scale about the same mental health inventory above the same the only difference we found was in something called the pain disability index which measures as I mentioned before how much pain do you have how much does pain interfere with your everyday activities and here we had this interesting effect which was that it didn’t matter whether you had received the epidural before or after incision it mattered that you had gotten it so receiving the epidural whether before or after led to people reporting less disability three weeks later than patients who had received the Sham epidural and then this slide here just shows if we had not I like to show this because if we hadn’t include that third group that received nothing this would have been what’s called a negative trial and then people would have read it and erroneously concluded well you know there’s no difference between giving it before or after so it doesn’t matter whether you give it which is really not the right conclusion so speaking of conclusions conservative estimate of the one year incidents of moderate to severe chronic closer to the pain is 0.5 to one percent in adults but as you saw that is really conservative and it seems to be higher in children but there’s only that one study at this point intra-operative nerve transection and injury is a causal sometimes non-modifiable risk factor

that should be avoided at all costs the presence and severity of pre and acute pain are risk factors for the development of long-term pain and grownups and children but we still really don’t know is it causal or not or what part what aspects are causal pain catastrophizing is a risk factor for chronic post-surgical pain and in some cases pre-emptive or preventive analgesia can have a beneficial effect in minimizing the likelihood that pain transitions into chronicity so with that I want to thank you very much like it’s an hour now I apologize for talking for so long but thank you very much