Captioning sponsored by Rose Communications from our studios in new york city, this is charlie rose. Tonight we continue to exploring our brain with the conversation about pain. Pain serves a very important function for us to survive, it teaches us what to avoid and lets us know when to seek medical help. At the same time, though it can create tremendous suffering. St. Augustine once said the greatest evil is physical pain, 100 million americans live with it every day would yo would wouo doubt agree, pain knows no boundaries, regardless of age and race, beyond the physical symptoms the experience of chronic pain often leads to feelings of isolation and hopelessness. Laura klein had been living with pain since a knee injury in 2008 and joins me this evening to speak about her experiences and Incredible Group of scientists are also here to discuss how we perceive and process pain, david bar stiewk of Childrens Hospital and david julius of the university of california, san francisco, allan basbaum, also of the university of california san francisco, Robert Dworkin of the university of rochester and once again my cohost dr. Eric kandel a nobel laureate, and a Howard Hughes medical investigator. Our subject is pain. Hrchl is really one of the great unmet medical needs and enormous problem in society. And the most, in the most general terms, bain is a unpleasant sensation in response to a real or potential threat of body injury, and it has an extremely important defensive damnive role, it is designed to remove the injured part of the body from the source of damage. And usually this is transient in nature, but with some diseases, such as cancer or arthritis, it becomes persistent and becomes not an damnive process but, adaptive process and part of the disease itself and adds to the pain. As we will hear from laurie klein, chronic pain is a disease in its own right. As these arguments make clear, this is an enormous Public Health problem. 100 million americans as you pointed out suffer from pain every year, and it is the most common reason people seek medical attention. There are two kinds of chronic pain, inflammatory and neuropathic pain, inflammatory, receptive pain is damage to soft tissue and it shows the adaptive role of pain perfectly, it is designed to move the injured part of the body away from the damaging stimulus, so as to prevent further damage from occurring, and to allow the reparative processes to take place. But sometimes sort of a hypersensitivity develops with as a result of the inflammatory process so that relatively noxious stimulus like just touching the hand feels painful to the person. Inflammatory pain is due to damage of soft tissue, but neuropathic pain involves in addition to soft tissue damage actually damage to the nerve fibers themselves. And this, not only involves hypersensitivity but spontaneous pain and burning pain. More over, it shows an interesting phenomenon that we see with laurie klein, and that is a phenomena of sensitization where the pain spreads from its initial site of injury to other parts of the body, for example, if i damage my fingertip, with sensitization it can spread up the finger to the hand, the forearm, all the way reaching to the shoulder. So this is really a very serious process, that can cause a great deal of pain for the person. These processes need not be independent, so inflammatory and neuropathic pain can occur together as is lauries case, the inflammatory and can lead to neuropathic pain. One of the remarkable things about pain is that we have made enormous progress in understanding it, in the last two decades. Our understanding of pain until recently was amazingly limited, it is the most mysterious of all sent tall at this and only. Recently made significant progress and the people around the table are major contributors for this. One of the first people to think about this was a stot until the fourth century before christ, and he thought pain was do two the fact an evil spirit entered the body at the sight of injury. Rose punishment from god. Punishment from god and it persisted through the middle ages into the renaissance, these are bad people and thats why they were suffering pain. This changed in the 17th century with this great philosopher, mathematician, rene december katrina, descartes, who developed a different view of pain. He thought of pain as a biological process and drew this wonderful drawing of a young boy being burnt. His toes being injured, and finers were carrying the information about injury directly from the toe into the brain, although the details of this model are not what we view as the pain process the general idea that it is a biological process is the current view. But the question is, what is the nature of the biological process. It is remarkable to realize that until 20 years ago, we did not have a good understanding until of the nature of the biological process involved. People thought that pain was very different from all of the instrumentalities, for each modality you have different receptors like rods and cones in the rhett na, you have old factory receptors old factory receptors in the nose. Each one has a private line, receptors specific to it and nerve fibers that lead to it. Rose hear, feel, touch. Exactly, with pain people thought that it may not have a system of its own, that it hijacks other systems and doesnt have receptors of its own. For example, many people thought that pain was the touch system, tactile system that were firing inappropriately. We know this is wrong. Many of these are small caliber fibers, many are these are finers that are specific to mechanical pain, cerebral pain and chemically induced pain. Rose and this is a breakthrough is. This is a major breakthrough and another occurred when we began to identify specific receptors that mediate this, and david julius who is here was one of the people who characterized one of these receptors. These are iron channels called trip channels, they respond to both thermal and chemical stimuli, this is a wonderful advance, and a major scientist in england jeffrey wood discovered tactile pain receptors. He discovered a group of kids that actually began with a pakastani family, then extended it to others, congenitally insensitive to pain this was written up in last sundays new yorks time. These kids are feelers, they can put their hand into boiling water without even being aware they are doing it. They dont feel pain so the whole defensive function of pain is lost for them. They do unbriefably, unbelievably still litigate things and Dangerous Things because they dont have a fear of pain because they never perceived it. So this turned out to be due to a sodium channel and that is also interesting because we have sodium channels all over the body, thats how we generate action potentials but this is a special kind of sodium channel that carries this particular kind of mutation that gives rise to insensitivity to pain and another mutation in that channel gives to hypersensitivity of pain, so for the first time we were getting a profound understanding into the nature of pain, often a, not only in a biological but in a psychological sense. We will see as we discuss lauries injured which occurred in a gymnastic competition that unlike many of the things in medicine, you cannot measure pain objectively. It is a completely personal experience. So your response to pain will vary depending on the context in which you experience it, whether you are attending it or not, your sex, physicians have to learn how to listen to patients very carefully in order to really appreciate how in particular person is responding to pain and we are going to see as we go around the table with these four people, each of whom have pioneered a different aspect of pain, how not only clinical sensitivity but also important advances in biology have brought us to a new level. Rose this is the New York Times article base says blockers, ashlands life would be a lot ease yen we she stuck her hand in a pot of boiling water she could feel it, go ahead. As eric noted there is no measure, there is no blood test for this disease and for the patients it is a silent disease and so we are dependent on speaking to our patients and trying to extract some concept of what they are going through, and the two issues that come through in terms of trying to understand an individuals pain relate to pain intensity and the emotional background related to pain. And without understanding those two factors, it is very difficult to actually appreciate what patients are going through. And i think in reality, many patients end up not feeling that their clinicians really understand their problem, and for those of white house are in the clinical domain of pain treatment, it is very tough when we dont have a specific diagnosis. Rose so let me talk to laurie. First of all, i want to stay how much we appreciate you coming here and sharing your own experiences. Tell me about the pain you experienced and how it evolved. Sure. Well, i was a gymnast on the club team at the university of texas at austin, and i was competing in gymnastic meets during the spring of 2008, and in march of 2008 is when i had a really bad knee injury when i was vaulting, this is a picture of a tina and i before one of our gymnastic meets. This is the event that i got hurt on. This was the actual picture right before i got hurt, and i was vaulting when i landed, basically blew my knee out and just had extensive damage to my knee. I tore a lot of ligaments. This is just 24 hours after that injury, and i had severe bruising and swelling and severe localized pain in my knee. Basically, i did not have Reconstructive Surgery until august of 2008, so that was about five months later. And after that surgery, there was a difference in the pain that i felt. It started to spread through my entire left leg, from my knee all the way through my toes, as opposed to just my knee. Rose what did it feel like . It was like a burning, a very severe burning pain, and then also kind of like an electrical jolt, where you kind of felt like you could feel things firing off in your leg. And then i also had sensitivity to touch. Rose right. To where i couldnt handle feeling the bed sheets touch my leg at night. Rose and when they did, what would you feel . Extreme burning pain and just it felt like my leg was kind of on fire, it was just really uncomfortable. I think this shows in a very interesting fashion two characteristics features, one is that innocuous stimuli now becomes painful and, two, the sensation, from the initial site of injury to involve the whole leg. Rose right. And then some of the other things that happened was there was a color change in my left leg and foot and it was kind of red and sometimes it would be purple and then i also had extreme teach change just in my left limb to where it felt colder, and other things were i had abnormal hair growth where the hair on my leg would grow a lot faster than on my other leg, and then my leg would feel pretty sweaty and kind of clammy, and then my the skin on my shin and my leg was very shiny, so these were all Different Things i had not had at the original injury. Rose and what psychological changes were going on . Well, i definitely developed extreme anxiety. I had a very hard time sleeping and not only because of the pain but then constantly worrying about, oh i am not getting any sleep and i cant stand things touching my leg. And i also had you know, i was very afraid of people kind of running into me or hitting my leg, bumping into me or even just reinjuring my leg itself. Rose and what were your doctors telling you at this time . Well, immediately after my surgery in august, they were just telling me that this was normal postoperative pain and symptoms, but it wasnt until about two months after, in october, of 2008, that we finally well my doctor fenylly accepted that Something Else was going on, so thats when he recommended me to a Pain Management doctor, who then gave me the diagnosis of complex regional pain syndrome. Rose and how long was this after the injury when you got that analysis . Six to seven months after. Rose . Before you realized this was an example of stream pain of which they needed special response . Right. Right. So where i actually was referred to another doctor to see what was going on. And it was very nice to get a diagnosis, just because i knew something was going on but then again, it was also not great because i never had heard of complex regional pain syndrome and i had never met anyone who had it before so it was all very new to me. Rose david julius, tell us, you know, where do we take this now . Well, our records, as we alluded to earlier, the study of pain was in its infancy and blossomed quite a bit in understanding the mechanisms and pathways that are involved in acute sort of pain that laurie experienced and then subsequent to that how changes in the system lead to these chronic pain syndromes. I think the big breakthrough intellectually as eric said was the realization that pain is really not that different than other sensory modalities that it shares some overall characteristics and namely that neurons, neurons are specialized, there are specialized lanes or groups of cells in the first slide, we can see that if you take a crosssection, for example, we would look through a crosssection through a nerve bundles such as a sig sciatic ne that runs through your leg you can see right away there are different kind of nerve fibers and some that are large diameter and wrapped with a thick insulating myelin sheet and others that are thin diameter and lack any insulation, and the form of these, the large cells are really the ones that the a betas are devoted to the detection of things that eric discussed, light touch, vibration, innocuous stimuli, we regard as not important, what we call c fibers receptors are the ones that really carry out the majority of signaling in with regard to how we detect painful stimuli and are the ones that sense knock noxious heat, noxios cold, noxious pressure and send this information to the spinal cord so we can see this general outlay is the, is of the system, so these are carried out by the c fibers on injury, and go to the dorsal horn and these messages are transduced through a number of synapses to the brain, where we cognitively understand this as a pain response, and so for example, these c fibers would be the sorts of neurons that were initially activated when laurie did this vault and hurt her knee and felt this acute pain. And the other big breakthrough in this field, as eric alluded to was really to understand the Molecular Devices that make the c fiber receptor know what it is, in other words the proteins that endow these cells with the pass to detect noxious stimuli and transmit this information to the spinal cord. And i just wanted to, i think there are basically two interesting discoveries in this area that are worth highlighting, and one is the discovery of a family of molecules of ion channels we call trip channels, these are found on a variety of different c fiber receptors shown here and the way these were discovered actually was as targets for a number of irritants that we experience, natural product irritants in our environment, the most familiar is cap say sin the pungent ingredient in chili peppers that give them the hot burning zinc and it turns out it rely sits that response. By binding to the receptor, called trip d 1 and when it does so it activates a nerve fiber, initiates an electrical potential, change and we sense this as a burning sensation. This is why we sort of conflate the experience of a hot chilly pepper with a burning experience. These ar are all in the last ten, 15 years . Ten, 15 years and trip eight which is a receptor for a natural product from menthol which we all experienced the cooling phenomenon and it turns out this channel is also activated by cold which is again why psycho physically we experience a mentally cold sensation and other such molecules and all of these play defined roles in allowing sub sets of these c5 receptors to detect noxious heat, cold, et cetera. And then the other another big discovery that eric alluded to were these this family of sodium channels, he said sodium channels are present in every neuron in the body, but c fibers actually are a subset of c fibers reflect a certain subset of channels and this has really come to the fore because of people who, such as the one described in the New York Times, individuals who have mutation ms. These channels, and these. Mutations have very, have very profound effect os ten pain transduction experience and these are responsible for taking the initial activation of the nerve fiber by capsasin or heat and conducting this to the spinal cord. They allow the electrocurrent to continue flowing and mutation ms. This particular channel have very profound and fascinating effects on pain sensation, in individuals in whom this channel mutations render it nonfunctional, they cannot experience pain, interestingly they can experience innocuous stimuli such as light touch but incapable of experiencing pain and as eric alluded to you can easily identify such children because they have they lack the protective function that the pain system normally affords us and do not know when they have burnt themselves or may be running around on an ankle that has broken bones, et cetera and this has grie grievous conseque0 for these kids because they have to be watched very carefully. To illustrate how dramatically the field is moving this is only six years old we discovered this. And then there is a flip side of such mutations in which people have mutations in the same channel that render the channel hypersensitive so it is sending signals ordinarily in the absence of any peripheral stimulus like heat, cold, et cetera and in these individuals they have ongoing chronic pain that is unlinked to any peripheral stimulus and these patients will come into their see their physicians sometimes with their hands or feet in buckets of ice water because they feel such extreme burning pain at their extremities and so these studies really show that these nerve fibers are functionally and molecular specified to carry out this process of pain 7ation, and we are beginning to identify some of the. Molecules that endow them with these properties. Tell us how the pain goes from the receptors to the brain. The key thing is that the information travels from the spinal cord up to the brain and really accesses at least two major areas, because on the one hand you have the experience where is the stimulus, how intense is the stimulus . You have a century component to it you can detect, sensory component and there is an emotional stimulus it, and there are emotional areas of the brain that are activated and there are sensory disjimive areas so there is. No one pain area of the brain. There is a matrix of activity turned on in the brain and that causes the pain experience. But what is special in the setting of injury and chronic injury, the nervous system changes, the brain and spinal cord, of somebody who has experienced a devastating injury that laurie had is really an altered nerve vows system, in that sense there is a disease of pain and we can illustrate the kinds of changes that occur, the sensation, sensitization process, wherein noxious stimuli hurts, thats the problem, they say my arm hurts but what they are saying is when i move it i hurt, it hurts or when i put on clothes it hurts and there is really two major mechanisms to which that comes about. On the other hand, it is a rather simple one, out in the periphery, to the receptor itself it can be affected by the injury process, such that chemicals that are released on the onset of inflammation it lowers its threshold and you have changes that take place in the Central Nervous system and in the spinal cord about the inadequacy of paper education in america, so for example, in a survey of 100 medical schools, quite a few were pound to have only devote add couple of hours in their entire medical School Curriculum of four years to pain, so there is this enormous problems in terms of social burden, personal burden and physicians in training are getting a couple of hours of teaching about it. Which is rose that is one thing i am surprised by. And finally the last thing the report says is the public needs to be educated, patients need better education about the pain they are suffering from and its treatments and the treatment n an antiepileptic drug called pregavlin or known as lirica and have been on that still to this day i have been on it since the day i was diagnosed until currently. And how is that work something. It is not that i can tell it is working. It is not like i take it and i say oh this helps, i feel better. It is more if wrote take it i notice a difference in the pain in my leg and kind of how my leg feels and kind of the nerve firing in it. Rose right. So then what we did because nothing obviously was helping with my pain, i had a number of injections in my back called lumbar sympathetic nerve block, and basically this would essentially block out the pain and it worked great, except that what was explained to me is that they were supposed to build on each other so that the time inbetween each injection would get longer inbetween each one so eventually i wouldnt need them anymore, unfortunately, that didnt work for me, and about every four to sticks weeks, it would wear off and all of a sudden i was in extreme pain again. So then finally, in july of 2009, we decided to go ahead and i got a spinal cord stimulator implanted in my back and that was, to me, at that point, it was the miracle device that i wasnt having to be put under, you know, and having medical treatments anymore, this is just kind of there, and i wasnt taking any medicine or rose no more pain . Well, at that moment, i thought i wasnt in pain. It worked really well, but at that time, i also was very inactive. I was staying in bed a lot. I wasnt really doing much. I had finished school, but i couldnt get a job because of everything that was going on with my condition. So it was when i started Nursing School and in august of last year that i realized, okay, maybe this isnt working as well as i thought it was. Because all of a sudden i had, you know, the typical student anxiety and stress of being in school and having to be up on my feet and in Nursing School having to work clinicals, and the i realized that, okay, my pain is actually a lot worse than i thought it was. So this past july i went and had an experimental treatment done where i had a continuous iv infusion of camene over a period of four days, four hours each day, and that was the one treatment that i can say that the others helped manage the pain, but this one actually i felt like was a cure, and after that, i am my anxiety has mostly gone away, except for the typical student anxiety, and then but i would say on my worst day, and maybe i maybe feel five percent of the pain that i felt before i had the treatment. Rose so what do you say about these treatments . Well, she has had many of them, that is for sure. And if we can sort of go through the different approaches. Now it is interesting that you got some effect of the opiates very early and then eventually they stopped working and thats one of the characters, opiates are the most commonly used drugs for the treatment of pain other than aspirin like drugs, they are very effective and obviously have problems associated with them so if you look at one of the slides that illustrates the top down control system, that not only does information go from the spinal cord to the brain, but the brain actually has the pass to regulate, capacity to regulate the output of the spinal cord and that involves the endorphins, so when you you can naturally control your own pain if you are able to, you might be using the endorphins but what it does is substitute for the endorphins and turns on the control system and the brain gets less of a pain message, that tends not to be very effective for the neuropathic pain that laurie has experienced, the nerve injury associated pain, and that is because there is a very different process that occurs, and we look, if we look at a big blowup of the spinal cord, in the next slide, what we notice is that there is a neuron that is labeled an interon, that is a inhibit toir neuron that outputs the spinal cord, when you have nerve damage as laurie had, those cells can be lost or their function deteriorated, so there is no local control, one of the ways to treat that is as if you are trying to treat an epileptic type condition because when you have a seizure you lose those controls, but in that case in the cortex, and it turns out for neuropathic pain the first line drug are the anticonvulsants, and they can before very effective, unfortunately they only reduce the pain somewhat and in only a certain percentage of patients. The brain stimulation or actually laurie had spinal cord stimulation is an interesting process on the one hand it may be electrically stimulating some of the areas that are descending from the brain, the other likely case is if you burn your hand one of the first things you do is you shake your hand and what you are trying to do is you are bringing in certain types of fibers that have the capacity to regulate the output of the cord by putting a stimulator in the spinal cord you can stimulate many of those fibers in a kind of backwards crazy way, and regulate the output of the cord. And when it works it can be pretty spectacular as obviously is the case with laurie. How does cadamine work. It is a very complex drug. Some people use it, you know, it is a psycho stimulant. It had the capacity to block a major nerve transmitter that is throughout the ba brain. In part we believe it is working on what i refer to as the central sensitization process and toning it down, but when you get effects that are so dramatic that laurie described, it is almost certainly working at all levels of the brain. And i would be lying if i said i really could tell you how it is working in the brain. Robert dworkin what strategies are used other than those we are talking about . I think lauries story is really unusual in the sense that now he is talking about having pain at five percent of what it was. That is really not what commonly occurs. We have all different sorts of medications we have discussed a little bit up to now, and medications that are effective for neuropathic pain arent the same as those that are effective for musculoskeletal, low back pain, osteoarthritis and for other conditions like fibromyalgia for all of these pain conditions, what typically, unfortunately is the case that no more than maybe 50 percent of patients get some benefit and can tolerate the side effects, and, unfortunately, those 50 percent of patients who get a benefit dont have pain that goes from, say, eight out of ten to one or two, but what laurie is describing, what is much more common, if their pain goes from 8 00 to 5 00, and if they are really lucky it goes there eight to four there is a 50 percent reduction, so when that partial effectiveness of treat treatment is that often medication. Medications are used in combination so a patient might take an antiepileptic drug along with one of the antidepressants that also have analgesic effects so medications are used in combination and what we think by using medications in combination you get some what of a boost in the effectiveness you might get pain going from eight to four or three, rather than 8 00 to 5 00. Then of course the other thing is that medications are used in combination with nonmedication treatment. Laurie already described spinal cord stimulation and sympathetic nerve blocks but there are lots of other nonmedication treatments, so for example, obviously, physical therapy, times of psycho therapy like cognitive behavior therapy and all kinds of complementary medicine like acupuncture or tai chi oreo ga or, oreo ga, or, yoga, and although. You had these experimental dreams, typically the treatment of pain is a combination of different medications and other treatments like yoga or tai chi or physical therapy. How does cadamine work in. It is a very complex drug, some people use it, you know, it is a psycho stimulant. It had the capacity to block a major excite toir nerve transmitter in the brain, in part we believe it is working on what we call the central sense at this station process and toning it down, but when you get affects that are so dramatic that laurie described, it is almost certainly working at all levels of the brain. And i would be i would be lying if i said i really could tell you how it is working in the brain. But in part it is affecting the process of sense at this station you wanted to add. One of the problems i think that occurs as a result is that patients are very frustrated, if there is to immediate benefit, and secondly, we are taking time out, as it were in terms of their condition, so it can still progress overtime. And i think these are issues that hopefully in the coming years studies will actually provide real data where clinic his accounts treat patients with a dated, driven process, data driven process and hopefully with a personalized medicine approach. Rose what are the experiments that are underway, i mean in the laboratory . Well, obviously there are clinical studies, where new drugs are developed and they have to be tested. Rose on different models of pain. In the preclinical world we are trying to understanding understand the fundamental basis of pain transmission and processes where you can monitor mostly the hypersensitivity, just as it is difficult to tell if a patient has pain, i cant tell if an animal has pain, i can sort of infer, but the fact is, i can demonstrate hypersensitivity so if an animal has an inflammatory condition they will pull their brain away, their brain may not be activated and i can study the mechanisms so we have moppeds and they are only as good as they are predictive of the utility of a drug and amongst i think one perfect, wonderful example is, i said that opiates worked by turning on the brain, well many years ago it was demonstrated that opiates can also work in the spinal cord, actually inselect the drug at the level of the spinal cord and turn it off, because the target of opiates are there and they work in animals and when that was demonstrated it was taken to the humans so rapidly and now i would say it is one of the most common procedures for post operative pain, post se searchian pain and, post cesarean pain, so basically. You are trying to model the systems that the patient experiences. I think there is another issue that really emerges when you listen to this discussion, one of the reasons that pain is such an extraordinarily complex sensation and why it is so difficult to treatment is essentially it is a moving target. It changes the brain and it changes the brain all the time. So you are dealing with something which is recruiting more and more different processes in the brain, and all of these affect the perception of pain. And you cant see it. Rose but the brain is always changing, i mean everything is changing. It is changing with learning but in a more restricted way, this involves large areas. I think that is one of the potential advantages of imaging, i think it is still a relatively new approach, but it is in search of trying to provide at least a clinical assistant to patients, assistance to patients but at best a specific marker that can actually define a disease and its continuation and or its benefit to medication. Rose back to you, david, in this whole notion of what is in the pipeline . Well, i think one of the, from my perspective one of the an em competent us the for understanding how these sensory and nerve fibers work is to try to intervene early on, when a pain message is first initiated, because as alan said, the barrage of incoming information changes the spinal cord in the brain and so one of the attractive approaches would be to turn down those messages as they first come into the spinal cord. After there is an injury and activation of the merv fine they are is a sort of cycle of activation of the nerve fiber, enhanced inflammation and things that we see for example in arthritis, and so we know that some of the molecules that we discussed earlier, for example, are targets for some of these inflammatory mediators that change the game of the sensory nerve fiber so the goal really would be to change the gain of the, you dont disturb pain sensation but you change heightened sensitivity in the context of injury, and, therefore, change longterm changes decrease longterm changes in the spinal cord. You referred to the specific sodium channel that is abnormal or not functioning in the children, kids who dont feel pain at all. If you turn it around and say if you coddle develop a drug to target that and then control the level of output, this is a huge objective of the pharmaceutical industry, that is probably their number one target. It is a target that antiinflammatory agents we talked about so we would like to interfere with those. I think this approach is so critical, because in every area of medicine, the earlier you can interfere with the disease, the better the outcome. There is true for cancer and everything, and it is just as you indicated, in the last decade and a half, that we even know the molecular nature of these receptors. Rose there is youre to the brain here, does youre to the brain tell us anything about how pain works in the brain . Well, yes. It has told us a number of things and it told us first of all that there is a top down process that can regulate pain, and insofar as we can recruit it and there are a number of ways it can be recruited by placebo, for example that is a very testify way of recruiting it, we can eliminate or reduce or ameliorate some aspects of the pain so the whole discovery of the system within the brain that actually counter acts the painful stimuli is a very important discovery. Rose let me ask each of you two questions before we go. Where do you think we are going in the next five years . In all of the areas we have been discussing here, and what is necessary mess to do to get there . Well, i think two extremes. Eric mention plaid se doe bow and we havent talked about every physician has a placebo element, the physician believes it works and the patient must believe it works, some would think a placebo works and therefore the there is no real pain. We understand that the placebos stimulate the endorphin release and there are other molecules that have been identified, so perhaps you can develop drugs that would enhance the placebo component of your treatment on a totally different perspective, there is an approach, the notion can you treat the disease of pain . Now, emphasize that there are actually molecular and structural and cellular changes that occur in the setting of pain, can you actually treat that problem . And one of the approaches that is being used is stem cells. Stem cells . Stem cells, thats right or progenitor cells, the gab ba inhad been toir cells are lost or diminished in the spinal cord, it is now possible to replace those and actually ameliorate the condition. These are Animal Studies but no reason to believe that couldnt be taken forward. Rose go ahead. To address your question i think there are a couple of really big areas. One is, definding what the patient has, in other words, the pheno type, the second is to have proper trials that define the utility of medication, or whatever treatments are provided and the third is to have a metric, whatever it turns out to be, whether it is imaging or a blood test, it would seem without this, we dont really know how to mess our treatments. I agree that one of the important things in the next few years will be to have more objective measures of pain, so, particularly i think imaging would be promising there so when somebody comes in, they dont have a physical manifestation of that, you can there will be sort of a more objective diagnosis, but for my own perspective as someone who studied these molecules we have just identified some of these molecules, and i mean the minute in the last ten years of so and there is tremendous potential for Drug Development to hit new targets and in terms of what we were talking about before one of the other advantages of hitting targets not just valley but peripherally is to sort of further the the clos closer u are the more proximate you are to the damage the more effective the medications can be. So you avoid some of these problems i think ideally what we are looking for is the equivalent of an antibiotic, where you have specificity and efficacy without a side effect profile, because many of these drugs actually work very well in terms of efficacy, but they are killed in trials because of side effects, and bob dworkin can speak to this issue. David alluded to this, figuring out ways based on the patients signs, like laurie, burning and stock like pain tells us what tells us about the physio abnormalities and if we can use this as a window to the underlying abnormality, maybe we can target treatments to those specific path though physiologic mechanisms and ultimately develop a. More personalized Pain Medicine that is more effective. That is number one. Number 2 is preinvention and prevention, prevention, prevention. I think that there are all sorts of models of how we can prevent pain, preventing chronic pain in people with shingles and chronic low back pain i in patient whose have acute back pain, and preventing pain in patients following surgery about 20 percent depending on the surgery of patients following surgery have pain six months later so i think we need to start spending a lot more time figuring out what kind of interventions given immediately when the injury is occurring might prevent the longterm chronic pain, which is not doing that, unfortunately. Rose tell me where you are, you have talked about this dramatic reduction in pain, and what do you most want now . I think for me, what is important now, being in Nursing School and eventually going to be a nurse is, really the education component of it. I can say from my specific experience that at least in my nursing School Curriculum, we are talking about pain, more and more, but i was very you can can i to have a doctor, even though it seems like it kind of took a little while to diagnose my pain syndrome, in reality mine happened a lot faster than other people, especially now that i am starting to meet other people with the same condition, and, you know, i was lucky that i had a doctor who kind of knew something about it and was able to specifically refer me to someone who treated the condition. A lot of people, i have talked to a lot of people who their doctors dont believe them, they are telling them they are making it up and they have been dealing with these major this major pain condition for years, and even though i have had it for almost as long, i can say that my, i guess the course of my symptoms and treatment was probably a lot easier than some other people, just because we were able to specifically kind of do certain things or i didnt have to fight to convince anyone that i had this condition, more than like two months, so i really think it is important that the public is better educated like we said earlier, and that more doctors in the medical profession. Rose and spend more time on it. Right. I want to make one point. One reason we selected this program to come, talking about atherosclerosis it shows the extremes. You have a single cell type that is damaged, and here we involve the whole brain, so this is really an extremely, probably as complex disorder as you can come across in Brain Science, and we have to remind each other that even though you and i enjoy Brain Science enormously we are at the beginning of a Great Mountain range, there is much of Brain Science we dont understand and i think pain brings out how much more we need to learn, so i think the fact that the methodologies are moving along, imaging is now being used in a more routine way to study pain, molecular pain receptors there is only a decade and a half old and we are realizing that there are connections between this and depression and we see the same neurocircuits are being recruited, this will help us get better understanding and better treatment. Rose thank you, thank you, thank you, thank you, thank you very much. Thank you. Rose where to we go next . We discuss another pain condition, posttraumatic stress disorder this is not only important in military personnel who have a high percentage, but also civilian populations after a brutal beating, people experience this and we begin to get an understanding of it and also getting therapeutic approaches to it. Rose i look forward it to. So do i. Rose thank you for joining us, we will see you on episode 12 next time. Captioning sponsored by Rose Communications captioned by Media Access Group at wgbh access. Wgbh. Org narrator explore new worlds and new ideas through programs like this, made available for everyone from contributions to your pbs stations from viewers like you, thank you. Next, music legend petula clark hosts an allstar reunion from the bands that made the british beat. [music playing]