[00:00] Thank you very much, I would like to thank the organizers for putting this wonderful symposium together and inviting me to give a talk on pain which is quite a daunting task as you heard Dr. Greenburg (note1 ) this is one of the more challenging symptoms that you that’s ubiquitous in the CNS inflammatory disorders. So, in the short time that I have I am going to try to give you a potpourri of the various pain symptoms that we see in these various conditions many of these pain syndromes that the audience suffers with. In my day to day life in treating in patients I would say that pain is probably one of the most difficult symptoms to treat and I hope if you remember anything by the end of this short presentation you remember that treating pain really take a multi-disciplinary approach and a multi-faceted approach and it is just not about the medications and we have to think outside of the just medicines.

[01:09] I have no relevant disclosures to this particular talk outside I am not a pain management specialist, so that is a little bit of a caveat from a neurologist point of view. I am going to briefly talk about two of the standard definitions of pain that many people agree about. I am going to spend a minute on basic characteristics of pain, then the majority of the time I am going to review the various pain syndromes that we see in these inflammatory disorders and really focus the attention on the spinal cord related syndromes, because in my view that seems to be where the trouble comes from. And then we’ll briefly talk about some of the treatments that may be successful.

[01:57] So, in the late 1960’s a pain specialist nurse Margo McCaffrey defined as whatever you see there, “whatever the person says it is, exiting whenever and wherever the person says it does”. Now I really like this quote because I think it does encapsulate in a broader way what pain is, verses what the American Academy of Pain Medicine, so I told you I am not a pain doctor so I can bash this a little bit. But “an unpleasant sensation and emotional response to that sensation”, now it is quite vague and doesn’t provide a lot of information so I like Margo’s quote much better.

[02:43] Now the Characteristics of Pain (note2 ) you I think many of you could go through this and tell me what it is and pain is very complicated, is a sensory phenomenon, it involves a lot of the central nervous system after its been damaged and you saw very nicely done by Dr. Pardo going through the anatomy of the nervous symptom (note3 ) and when there is a disruption of the in the sensory pathways as we see in transverse myelitis that sets up for future pain syndrome. Now the problem with pain is when you go into the clinic and we ask you what is your pain out of zero to ten, it’s a useless scale it really is, it really does not help the clinician get a good idea of how severe the pain is and unfortunately still in this day and age we don’t have very good ways to measure pain there is a visual and analog scale that is a little better and it is out of a hundred so some of my patients I will ask them out of a hundred where your pain is. Scales can sometimes be useful if you are with a provider longitudinally this get to know you and you build a relationship then you can see where that person is on those scales to say alright, are you having a good day or a bad day, so it has some utility but not a lot. And pain interestingly is very individualistic there have been a number of studies looking at why do some people have pain show up in certain ways, why is it more severe in some individuals’ verses others when they have the same attack to their nervous system. Some of this may be how you grew up and how you are taught to deal with  pain, so it is very complicated. And why do we care about the primary ideology of the various pain syndrome or syndromes is so we can target the therapy accordingly. And I will go through some of that in a little bit.

[04:42] So, transverse myelitis or myelopathy as you heard comes in two flavors the acute pain where some of you have had TM at the onset had severe back pain that comes with it, but I would argue that it is the chronic pain syndromes that are the most difficult to treat the most problematic and across the board majority of people who have had some spinal cord attack have had some pain syndrome. Now many of you can tell me and you can hear this in the clinic that there are various triggers to the pain that you can see the list there (note4 ) so if you don’t get a lot of sleep one night, you wake up the next day you maybe in more pain. If you have an infection or you’re exposed to excessive amounts of ambient heat that may provoke some of the pain. There have been a few studies but not a lot that have demonstrated that the severity of the attack does correlate to the severity of the pain syndrome, for example we know with certain conditions like Neuromyelitis Optica where the spinal cord attacks that occur can sometimes be a lot more robust and cover a larger area of the spine verses MS that the intractable pain syndrome seemed to be worse for that condition at least for a couple of studies.

[06:04] So, I am not a radiologist but I actually have a lot of disclosures, I didn’t realize, but I am not going to go through this in great detail but to get the point across that pain syndromes are more significant with the worse TM attacks. So, this is a patient of mine that has Neuromyelitis Optica and suffers daily with a variety of pain syndromes. This is a patient of mine that has Multiple Scoliosis who has some pain syndromes but it doesn’t seem as severe as the NMO patient. (He is pointing to pictures of MRI’s of spinal cords)

[06:45] So, this is a busy slide. But, when we look at pain syndromes, at least when I look it, I’m trying to think of categories so where does this particular pain that a person comes in with fall within these categories so we break in into Primary, Secondary and Tertiary by in large the most common is primary pain syndrome so it is directly related to the neurological attack and the injury that ensues from it and some of the things that you know well neuropathic pain, tonic spasms and Spasticity so I will go through a couple of those in more detail. The secondary pain syndromes and also the tertiary pain syndromes, at least from what I’ve seen, often are not paid attention to and I think it is very important to be mindful that not all pain is neuropathic pain. So, there certainly could be a muscle skeletal pain component if someone has had a spinal cord attack and their gait is off and chronically your gait is not functioning normally that’s going to put wear and tear and stress on various parts of your joints and body that are not have used to having such a load and that over time will cause many problems. The tertiary pain is I wish we could have a whole symposium on tertiary pain. When individuals have chronic pain syndromes they developed into a very bad vicious cycle including emotional issues depression, and I don’t have to tell the audience here it is very challenging. What I do try to relate to residence and fellows is that if someone has chronic pain you have to look at these secondary and tertiary pain syndrome categories and treat those just as much as the primary pain syndromes else you are not going to break that vicious cycle.

[08:42] So, within primary pain neuropathic pain seems to be the most common and, of course, it’s at some level it is the most disabling as you can see there, there is many ways we can describe neuropathic pain or you guys will describe to us the burning, tingling, squeezing sensation, electric shock like pain. I saw someone just this past week who has a Lhermitte’s sign that ever so often it comes back with a vengeance. No new lesions on MRI it’s just from prior damage but this is one of the most disabling symptoms that she has so we’re currently trying to modify her pain treatment. The challenging thing with neuropathic pain is not only can it be continuous but you can have the severity change throughout the day. So you may wake up in the morning and feel not so bad so you go to work or go to visit a friend and all of a sudden your pain level go through the roof because of the activity you are doing for that particular day, and it is somewhat unpredictable. The one that hear in clinic that is probably one of the challenging things with neuropathic pain is here you are coming home and going to lay down in bed an go to sleep and boom there it is it kicks in you can’t get a good night’s rest then the next morning you are fatigued and that revs up the pain syndrome again and the pain continues. What we’ll see so some clinicians and some patients doing on their own is trying to take over the counter ibuprofen, Aleve for neuropathic pain. Because of where the injury is occurring and the type of receptors that are involved the standard analgesics do not work. And as I have alluded to all ready it does take multiple therapeutic interventions to treat certainly neuropathic pain in others.

[10:44] So, still within the primary pain category there are the intermittent pain syndromes and I mentioned earlier the Lhermitte’s phenomenon. I don’t know have you raised your hands have any of you experience this Lhermitte’s phenomenon where you flex your head forward and you get this bolt of lightning right down. It is quite disabling; quite problematic it will just happen you will be out having lunch and you move your head the wrong way and boom! Zap! you get it and anatomically it is the back part of the spinal cord that gets involved. Now this doesn’t necessarily go hand in hand with just neuroinflammatory conditions if someone has bad disc disease that is compressing the spinal cord they can get Lhermitte’s as well. Painful tonic spasms I seen a number of individuals who this was there presenting symptom of their neurological condition and there was a nice paper that was just done in our group that led by doctor Levy for NMO that looked at tonic spasms as being very disabling and actually could be the presenting symptom in a condition like NMO there are very brief but really painful. Now this multiple scoliosis hug we have to get rid of that because any one with a spinal cord attack if you get this torso band discomfort and I have individuals in clinic tell me that they can’t breathe when this really comes on and this can be very disabling as well and sometimes can respond to medications as well that we prescribe for neuropathic pain.

[12:21] Now I have already touched a little bit upon some of the symptoms that we will see with the primary pain syndromes: insomnia, anxiety, depression, weight loss, of course decreased quality of life. There has been a number of studies that show that chronic pain syndromes really impact one’s quality of life and then disturbs relationships as well.

[12:41] So how do we manage primary pain syndromes? As you’ve heard me and it’s going to be over and over that we really need to look at this from a holistic approach and try to treat people with a multifaceted approach so medications, you can see the many classes of medicines there (note5) that we will use and will try to target different areas of the nervous system different receptors different channels. Often, we need to do a combination of these different medicines with different mechanism of actions to help treat the pain. Depending on the type of pain syndromes sometimes warm and cold compresses will help, pressure stockings, acupuncture. I have a slide dedicated to medical marijuana since it is all over the news. When we look at refractory pain syndromes where we have someone on multiple medicines, they’re doing acupuncture, they’re doing massage therapy, they’re doing the warm and cold compresses and there still not making ends meet. We will think about spinal cord stimulators. There is old ones an newer ones that that seem to be MRI compatible, that’s good because we like to do MRIs on our patients. Then there are the barbaric interventions that I have personally not referred any one to where parts of the spinal cord are chopped out from the neurosurgeon to try to decrease pain syndromes and at lease the studies that I’ve reviewed the problem is even when you chopped that area out that you think is the focus of the pain syndrome up to 30% even more actually have the pain syndrome come back and it can be even worse. So, I don’t typically refer people for those. Now there are other interesting techniques that are being used in the peripheral nerve world, the radio frequency ablation procedure for root disease. I’ve had a couple of patents actually undergo that and sometimes it helps.

[14:45] So, we are going to go over these types of medicines in great detail (note6 ), exactly how they work and then there is going to be a quiz at the end. Now believe it or not this is a shorten list of the various pain medications that we will try on people and on the prior slide when I showed you the different classes of medicines these are some of the medications that are in these classes. What the good news is when you try one medication and it doesn’t work there are clearly many other medications that can be tried. Often, we do have to do a combination of treatments, two or three medications actually at the same time at different dosages. And it can change over time as an individual get older their body changes and so does their pain needs and their pain intervention needs.

[15:36] With respect to pain medication though, at lease my approach to this that I really start low the lowest possible dose with the medication and gradually titrate it over time. The reason being is that the medications have some significant side effects so if we put you on the maximum dose right from the start you’re not going to be able to tolerate it. We’re not like the epilepsy guys where they bring someone into the epilepsy monitoring unit they rip the medication off and they titrate off the medication really fast because that is a controlled environment. We don’t have the luxury to do that we have to treat this as an outpatient. Now I have already alluded to that most people have more than one medication to help with the pain syndromes, especially the more refractory ones and I would recommend if you are going to do multiple medications to look at the various mechanisms of actions of the drug and try to target the pain from different places the receptors and at the channel level that where your clinician and other providers to figure out but this is a good rule of thumb. Now this last point (note7 ) I put this in hear because some people will get some pain relief and for the chronic pain syndromes, especially the neuropathic pain, I don’t think that bullet point really relates to that. I think sometimes in the acute setting of back pain we will put someone on medications that we can taper off but most of the time that last bullet does not seem to apply.

[17:17] So, secondary pain syndromes muscular skeletal pain, it is like driving a car with square wheels, quite challenging. So, muscular skeletal pain really, I think goes under diagnosed and if I see someone in clinic that has ambulatory problems or is not ambulatory base on their attack but is in a wheelchair or whatever their mobility is I start to ask in a little more depth about the pain, where is the pain located, often the muscular skeletal pain even though it can be diffused is often localized in one area, maybe it’s the hip maybe it’s the knee. This is extremely important I missed doctor Becker’s presentation (note8 ) but we work closely together and he is from the neuro rehab prospective we send a lot of people to our physical therapist, occupational therapist, neuro rehab specialist to try to help treat this class of pain syndromes. And like I mentioned for many people will be in the box of primary secondary and tertiary pain so you have to treat all of them independently but together.

[18:35] Now there are some issues that are iatrogenic where if you have multiple attacks of TM or central nervous system attacks we often will give steroids and there are some people in the community that will keep people on steroids for long periods of time. There is this condition Avascular necrosis which is basically a stroke of large joints, like the hips, the shoulder, the knee, which I’ve seen in several patients so we are sensitive to that if someone is have severe hip pain we needed to do imaging including x-rays and MRIs.

[19:15] So, how do we treat these secondary pain syndromes? Prevention is the key. So, if someone has disability where they’re gait is impaired for example getting involved in a very aggressive rehabilitation program is the key because that will help prevent some of the muscle skeletal strain that the person is destine to unless your keeping active keeping mobile, you know like that old adage if you don’t use it lose it its really, really true when it comes to the secondary pain syndromes. I am not going to go through that list under the PT/OT interventions (note9 ) but know there are various thing that can be done other things non-pharmacological, aqua therapy seems to work really well for a lot people even those who have higher disability levels because in the water there is no gravity so you can actually move in the water and move through joints that may not have been having much movement for years. I endorse other things like manual manipulation and acupuncture, yoga, etc. Now the medications for secondary pain syndromes or thinking about muscle skeletal issues we do use a variety of medications but this is where the anti-inflammatory, ibuprofen, Aleve, sometimes can help. The problem with that though if you take too much you are going to get rebound headaches, you’re going to get stomach ulcer sometimes kidney failure sometimes you have to be careful. You can see the other list you can sometimes we’ll use narcotic pain medication which I am not too fond of and then to try to help improve bone health vitamin D, calcium, etc.

[21:00] So, I’ll spend a couple of slides on Spasticity because this creates a lot of pain and often the Spasticity that results you may at least I’ve seen in clinic someone looks like they are extremely weak but actually it’s because their Spasticity is over riding and once treating the Spasticity they are able to move freer.

[21:25] So those pathways that Dr. Pardo was describing (note10) are intimately involved in setting up someone to have Spasticity and when demyelination happens in the various tracks that are mentioned there over time Spasticity will develop. And this is a phenomenon that when someone has an acute central nervous system attack usually Spasticity is not present very rarely can be, but it’s really over time people will develop it. So it’s a little bit tricky in terms of monitoring people in clinic because if someone has increasing Spasticity the first thing we are thinking is are they having more lesion develop because that certainly can happen but often times it really is without new lesions. And it can happen where you have a muscle and a tendon Spasticity can develop, I’ve seen it in the weirdest places. And it becomes important because if someone has diffused Spasticity and you are trying to treat with a whole bunch of different oral medications you’re getting side effects from the oral medicines you’re trying the nonpharmacological interventions and now we have to start thinking of more invasive including a Baclofen pump for example. Now what is interesting about Spasticity unlike some of the other symptoms including some of the other hidden symptoms of nervous system diseases is that cold temperatures aggravate it. So we will hear from some people that the summertime is the worse that really activates a lot of my symptoms even pain syndromes with Spasticity it seems to be cold dependent. Similar to other pain syndromes there is a variety of triggering things you can see on the bottom there: stress, infection, pain. So if someone does come into our clinic with increased symptoms it could be Spasticity or something else I am making sure there is not one of these triggers present, it could be a simple urinary tract infection that is actually causing this.

[23:24] Now this is an incredibly busy slide I am not going to go through it in detail. This is just to hammer home the point again that with any of these pain syndromes and Spasticity included we need this multi-faceted approach so that oral medications, rehabilitation, Botox injections can be quite helpful seem to be more helpful in the smaller muscles and not the larger muscles. If someone is having significant side effects as I mentioned to oral therapies and their Spasticity is really, really bad then we will think about some of the surgical interventions. Now we are not cutting tendons as much anymore and I would say with individuals with higher disability levels that have contractures and that is interfering with their daily routine hygiene sometimes we will ask the surgeons to look at that but I think fortunately with many of the interventions that we have nowadays we don’t have to go down that road. So intrathecal Baclofen pump has been around for a lot of years there is a pump now available that is MRI compatible so that’s very nice because we will send some individuals to get this and some of the advantages you can see there are if someone gets to much in the pump you just change the dose delivery so that’s nice. In terms of the side effect potential Baclofen if some of you are on it or have been on it at higher doses can cause significant cognizant fogging or significant bladder retention. So this particular way of administration you can do concentrated doses of Baclofen where you won’t have some of those side effects. Some of the disadvantages is it is hardware you have to have a surgical procedure; this has to be put in. I have had a couple of patients where the catheters broke, or have been dislodged and that can cause Baclofen withdraw which can be quite nasty and actually lethal in some cases. And you do have to get it refilled because the pumps are only so big and the cost its not insignificant.

[25:45] So medical marijuana a whole slide dedicated to this right. So I am in Maryland where this is not readily available but D.C. is, but this is not new, right, so cannabis has been widely used in various chronic illnesses including Chemo therapy related pain, cancer pain, also HIV and AIDS related pain. The challenge that we have is that the inhaled version we don’t have really great ways to measure going back to that pain scales measures how well it’s doing. And what we certainly don’t have nowadays and hopefully we will are studies in specific diseases saying yes this is a home run we need to use it. There have been a couple of studies recently looking at MS population and you know I do have some patients that do Medical marijuana that the pain level and the Spasticity to the most things that seem to be most impactful does seem to improve. However, the inhaled version seems to impact for some people their cognitive function and make them a little more foggy headed. Which when if you smoked pot when you were younger you weren’t thinking as clearly when you were smoking but anyways so I think we need to do better studies more studies. When you look at the different components of cannabis in general the psycho active component of it is what get people in to trouble in terms of the cognitive function and works really well for the nausea and vomiting and that’s why it is used in chemo therapy, so that the THC and cannabinoid component is the one we need to tap into more and that the one that seem to work the best on thing like neuropathic pain. But unfortunately, the natural cannabis the medical marijuana has more THC than the CBD component.

[27:58] But there are actually a couple of medications, one of which is FDA approved, Marinol, which some of you probably heard of has FDA approval for chemo therapy related nausea and vomiting and weight loss in HIV/AIDS. So I have used this actually in a couple of patients that have had refractory pain syndromes and I think for an individual it may help. Sativex, which is not approve in the United States as of yet but is approved in other parts of the world, this is a spray that people will do in their mouth and actually at least in the data that I have seen in some people that I have talked to it seems to help. Now just like any treatment is not going to help everyone but it’s another way that we can tap into pain syndromes from a different receptor cause cannabinoid receptors are throughout the nervous system and this may be on the horizon I different avenue to treat. There is another medication in this class that’s not used that often because of the side effects.

[29:12] Now tertiary pain, now this is a busy slide and given the time I not going go through this I just want to impress upon you guys that chronic pain syndromes set people up for a lot of these issues: social, emotional, cognitive, depression, etc. And we really need to treat this in combination with the pain else that vicious cycle is never going to be broken.

[29:38] And here is another hitting you on the head with this a multi-d approach to treating pain. Now, of course, there are a lot of potential players (note11) that can get involved in an individual’s care and this could change over time depending on the need of the person and this is just not for pain just any symptom associated with a neurological condition. And so I really encourage people to endorse this multi-d approach because I have seen it change lives.

[30:11] So in conclusion, pain syndromes are ubiquitous in CNS inflammatory disorders I would say it’s probably one of the most challenging symptoms to treat it’s what I refer to as a hidden symptom I’ve reviewed very briefly that there are a number of associated symptoms that come as a result of pain syndromes and their various triggers, which many of you know well. And again, using a multifaceted approach using pharmacal and non-pharmacal interventions at least in my experience are needed and having that multi-d approach is really critical. I wish there was a cookbook recipe that we could all follow as an algorithm, got this pain syndrome, OK let’s follow this pathway and it works 100% of the time. Nope it is not that easy unfortunately so you have to try one thing then try another thing try a combination of things and hopefully that will improve the quality of life. Thank you.

Notes:

1 Dr. Greenberg’s presentation Myelitis and Subtypes: Report from the International Myelitis Working Group https://youtu.be/4odz_XJU2iA

2 Pain is Complex; Pain is a sensory phenomenon; Pain is not adequately defined, identified or measured by an observer; Pain is an individual, learned and social response

3 Dr. Pardo’s presentation The Multiple Faces of TM, NMOSD and ADEM https://youtu.be/nJ28Tp6EZlc

4 Can be worsened by anxiety/stress, fatigue/sleep deprivation, heat/fever

5 antiepileptics, antidepressants, antiarrhythmics, topicals, opioids, etc.

6 Amitriptyline, Nortriptyline, Imipramine, Desiprimine, Venlafaxine, Dulexetine, Mexilitene, Lidocaine, Capsaicin, Lidoderm, Carbamazepine, Phenytoin, Clonazepam, Gabapentin, Pregabalin, Lamotrigine, Topiramate, Oxcarbazine, Zonisamide, Opioids

7 In general, when pain free for 3 months on treatment regimen, consider a slow taper.

8 Dr. Becker’s presentation Advances in Neuro-Rehabilitation https://youtu.be/H1o-rqjFe10

9 PT/OT assessment/intervention: Gait training, Assistive devices, Bracing/splinting/AFO, Seating, Exercise/stretching

10 Dr. Pardo’s presentation The Multiple Faces of TM, NMOSD and ADEM https://youtu.be/nJ28Tp6EZlc

11 Multidisciplinary Team Approach: Patient, Nurse, Physical therapist, Psychologist/neuropsychologist, Occupational therapist, Pain Management, Acupuncturist, Physiatrist, Psychiatrist, Orthopedist, Massage therapist, Neurosurgeon, Neurologist, Vocational rehabilitation counselor