Norman Marcus, MD talks about pain and Low Dose Naltrexone - 2018

Linda Elsegood: Today my guest is Dr Norman Marcus, who is a pain specialist. He has a fantastic background. Thank you for joining us today, Dr Marcus.

Norman Marcus, MD: Thank you for inviting me. 

Linda Elsegood: Could you give us your background, please?

Norman Marcus, MD: After attending medical school, I did an internship. In the old days, it was a rotating internship where I went through the various aspects of what a doctor might do. I decided to go on to do a residency in psychiatry. And when I was doing that, I, became very interested in mind, body interaction and following my residency, I did a fellowship in psychosomatic medicine.

While I was doing my fellowship, I was asked by the department of neurology at the headache unit where I was, at Montefiore hospital (they had the first headache unit in the world). I was asked to join them. They were treating patients with headaches in the department of neurology.and at that time I was interested in biofeedback because of the whole issue of mind, body interaction. So I started to evaluate patients with headaches and treat them with medication as well as the biofeedback. And at that time I was elected president of the New York State biofeedback society.

Following a few years doing that, I was asked by the department of anesthesiology to start the first pain centre in New York City in the department of anesthesiology. And I did that with a colleague, an anesthesiologist. And we together started and then ran together the pain centre at Montefiore hospital, which I did for approximately seven years.We had a multidisciplinary program where we're teaching patients how to manage their pain using nerve blocks at times and medication and psychological interventions and relaxation training. And then from there, I was asked by the department of medicine at Lenox Hill hospital to start an inpatient pain treatment program, which I did. That ran that for about 20 years. Then while I was there,  I was asked by the princess Margaret hospital  in Windsor to start a pain centre. And I started to travel to the UK, one week a month for three years. I have an appointment in Indian NHS, and I ran the pain centre there.

And while there, we got some significant publicity and we were on the BBC, BBC two, and we were on numerous television and radio programs. And  we were able to help patients who had persistent pain. And by that time, I was starting to focus on soft tissue.I was introduced to Hans Kraus, who was President Kennedy's physician for his back and France Kraus  had a.

technique and the conceptual model on assessing soft tissue pain, muscle pain, and the president at that time was being treated by another physician, Janet Trevell, and she was injecting Kennedy five or six times a day into his muscles.

When Hans Kraus came in he stopped the injections completely and said that the problem wasn't all the muscles that needed to be injected, but rather muscles that were very deconditioned as well as maybe some muscles that needed injections.But think of all muscles that are tender as a target for injection, like dry needling or something like that, didn't make any sense. And he had a conceptual model where there were four reasons for muscle pain. Tension is the number one, then a deficiency or otherwise known as weakness and or stiffness of key postural muscles. The third was the spasm, which is involuntary contraction of the muscle that you can't straighten up and it's very painful. And the fourth was altered muscle tissue called trigger points in most jargon when we're talking about these tender spots. But actually, Dr Krause's concept was more than trigger points cause he recognized that the area of the muscle.

that was causing pain, wasn't really in the muscle in the tissue, but rather the ends of the muscle where the muscle attaches to the tendon and the tendon attached to the bone is the most tender spot. It connected to that muscle, and that one needs to be identified. Therefore, the specific muscle that's finding a spot on your body isn't sufficient because the pain isn't.

generated from that spot. It's rather generated from the ends of the muscles, so you must know which muscle you're in. So he made that distinction. And his results when he would inject the ends of a muscle were dramatic insofar as he wouldn't have to re-inject the muscle. So the standard of care now in terms of people who were doing, let's say, dry needling or trigger point injections is to repeat the injections over and over again, quite often into the same muscle whereas Dr. Krause would be able to eliminate the pain by finding the muscle specifically and then going to the ends of the muscle and doing his protocol, which involved not only injections.

And what he used a lighter cane, just for comfort. He, it was the actual needle in the tissue that was doing the treatment. And following that, there's a three-day protocol, using neuromuscular electrical stimulation and exercises that were developed at Columbia University school of medicine in the late fifties, early sixties.

And  exercises were developed by studying 3,700 patients for four and a half years. And then he came up with an exercise program that he then administered to 300,000 people at the YMCA and studied twelve thousand of those patients in town who had an 80% success rate in diminishing or eliminating back pain.

And in patients who had had surgery for the back and had pain afterwards, that success rate was even higher. It was 82%. So those exercises then became the standard exercise at the YMCA called the Wise Ways to a healthy back. And they were given for many years until someone decided to change it. And without going into what actually happened, this essentially killed the whole awareness of these exercises, but we use them as a routine, part of the work that I'm doing. 

So when patients come in who have soft tissue pain, we diagnose one of these four mechanisms such as tension. John Sarno would be speaking about tension myositis.And now we know that there are mechanisms where if you are tense, it alters the neurons and your spinal cord  and makes them more sensitive to input sensitization. So we also test them for weakness or stiffness using the test that Hans Cross developed with his colleagues on your Weber called the Krauss Weber test. It's a very simple test, takes about two minutes  to implement. It gives you a lot of information.  They were palpating for tenderness in muscles to identify the muscle. And what happened was that I discovered  it wasn't specific enough that many people have tender spots throughout their body that don't necessarily reflect where the pain originates.

So you can have a tender point, and it may not be actually coming from there. It may be referred from another muscle, and it's almost impossible to know if you're pressing on a referral pattern or the actual pattern itself. I mean the actual muscle itself causing it, or where is this just a muscle that is receiving information from another muscle and all of this.

A complication of where the pain originates was explained to me by Sigfried Mensa. So I really began to understand what was going on on a cellular level, and on a biochemical level, through the work of professor Mincey and together, ultimately, we wrote a chapter together in a Harvard textbook. Carol Warfield is one of the editors of the textbook, and it came out a couple of years ago on the pathophysiology of muscle pain. In that period of time  I was elected president to the American Academy of Pain Medicine and served on multiple committees and became interested in how diverse the various treatments are for the pains that people complain of. 

I started the outcomes—movement in pain. To try to come up with some assessment where we could measure if a certain treatment was superior to another treatment, and that's been a work in progress for the whole pain community. It was something that I began  and we did our best to finish it, but it's still happening. And now it's a major goal and mission of NIH to come up with parameters to measure what is successful, outcomes and pain. And I've written a couple of chapters in neurosurgical textbooks on that.  Montefiore went to Lenox Hill hospital and then I left Lenox Hill hospital and went to NYU and became the director of clinical muscle pain there in the department of anesthesiology and taught students who were fellows in the Pain fellowship department of anesthesiology for ten years or so. In the last two years, I moved to Cornell where I have an appointment in neurological surgery and in anesthesiology, I'm the director of clinical muscle pain research, and I'm working together withmy colleagues and anaesthesia and neurosurgery to see how we can better define how soft tissue is an important element in patients who are coming in with a run of the mill back pain. And also those patients who are found to have a surgical indication for their back pain, but continue to have pain, despite a spot, an apparently successful surgical intervention.Why are they still in pain? And quite often it's because there's a soft tissue that was not identified as a source of pain. 

I was beginning  to tell you about the problems in identifying a specific muscle by pressing on it.  I've discovered that I could stimulate the muscles with a tiny amount of electricity, and I could much more accurately identify which muscle is the source of pain.I'm now working on a next-generation device with the Cornell school of engineering, the Meineke school of biomedical engineering, to develop an instrument where we can, have a software program that will show the clinician what are the various muscles in the body, in a region of which the patient complains of pain.

For example, if you have shoulder pain to 16 muscles that cause pain in your shoulder, how do you know which muscle is causing the pain? You don't, by pressing, you don't really know, but when we stimulate it with a tiny amount of electricity, and that particular muscle or a couple of muscles are painful, and the rest are not. Then we assume that those muscles are sensitized and are indeed the pain generator. And when we treat those muscles, generally we can eliminate the pain in the region of the body. For example, in that case, it would be the shoulder.  I had a patient who was coming to see me for knee pain, and this was about ten years ago or so, and he had 14 knee surgeries with the same orthopaedic surgeon, and every time she had  knee surgery, she continued to have pain afterwards, and she was given more.

opioid. In this case, it was oxycodone, and when finally she was receiving something like 3000 milligrams a day of oxycodone, a huge dose. 

She was coming in periodically for pain medication and she was functioning.although it was a huge dose and I wasn't entirely happy with it. But she was functioning and she had this extraordinary amount of medication and she would come in periodically, every month or so, and I'd renew the medication and then she didn't show up on one day. And I called her home, and her husband told me that she was hospitalized and said, well, what happened? Well, she had taken her medication and then she had taken an antianxiety drug, and she fell asleep in the bathtub and almost drowned and was admitted to the psychiatric unit of a hospital with supposedly a suicide attempt.

So I said, Oh my God, I was there and it was terrible. She was finally discharged, but spent about ten days there and then called me up, made an appointment, and she came in, and I said, how are you doing? She said I'm actually doing okay. I said, well, how's your knee pain?  She said I don't have any knee pain. Really? I said, well, you know, how much medication are you taking? She says I'm not taking any medication. Wow. You were 3000 milligrams a day.  So I said, well, what happened? So she said, well, there was this doctor who was there on this staff, his name is Hugo Franco. And he came in and  gave me some medication, actually gave me some naltrexone, and that helped me get off the medication so that I was able to go down to zero in 10 days.

So I said, Oh, would she have a lot of withdrawal? She said no, I had no withdrawal. So this is impossible. I mean, it's like one of these events saying, Oh my God, how could this possibly be? So I said, I'm going to call up Hugo Franco, and I did, which subsequently we became friends, and then he explained to me that he used naltrexone in an ultra-low dose to detox patients.

So much against what you know, was on the internet, for example, or, you know, never give naltrexone when somebody was on opioids, it was great because he explained to me that it actually made the opioids stronger if you gave it in tiny, tiny doses so that with a more potent effect, you could then start to decrease it because you were getting the same effect with lower doses and you could just keep on going down, which he did.

This was amazing for me. So I said, well, perhaps, this could be useful with other patients. So I started to use it with patients where I wanted to facilitate a reduction in dosage or to get them off of opioids completely. And I was able to successfully use it in that fashion. But I still idn't quite understand how it was working until I went to a lecture by Linda Watkins and, she explained the whole phenomenon of microglia and toll-like receptor number four and how the ultra-low-dose naltrexone wasn't blocking the mule receptor. And I hope that your audience understands that.

So the mule receptor is where most of the action is when you're using an opioid and pain pathways. The major factor when you have chronic pain, microglia become very important. And the receptor that becomes stimulated on the micro clear is called like receptor number four.

And when it's stimulated, it produces cytokines. 

 And many of these cytokines are pro-inflammatory, meaning they cause inflammation, particularly interleukin one and interleukin six. So these cytokines end up giving you neuroinflammation. It's sort of making more pain, pain on top of also gives you what's called illness, behaviour or sickness behaviour where you feel you don't want to interact with other people. You feel sluggish, you want to just retreat alone, sleep a lot. And it's like a survival mechanism. So if there was true trauma or you know, some injury in your body, the microglia respond by giving you these cytokines or producing these cytokines that make you want to just rest a lot and not interact and not waste your energy using all your energy for repair.

So I started to understand that the whole issue of central sensitization, which is what happens when patients have persistent pain. The issue isn't—all the receptors. We used to think it was that it was upregulation of the receptors so that you  needed more medication, because of the new receptor.But it was very much involved with the activation of microglia and that if we could suppress the microglia, we could suppress pain and actually reduce tolerance. That's some of the tolerance was a function of activating microglia. So I started to understand it would work for patients who had  central sensitization.t I've been treating a large number of patients for the earliest endless syndrome, and the most common complaint in that population is fatigue and pain.

When you examine them using my electrical instrument, they come up with anywhere from around 50 tender or sensitized muscles test positive. When I say the relatively normal population who just comes in, let's say with that pain, the average number of muscles, it's about five, so they have ten times the number of muscles that are sensitive to a small amount of electrical stimulation.And it would appear that they have central sensitization, because they are, sensitive to all stimuli, they do have a mood disorder and quite often they have something else that fits in the whole picture, which is mast cell activation syndrome. This is like another part of the puzzle that the mast cells, which are cells in the body that respond to trauma and to infection, to any assault in the body or to a foreign body,  they sometimes become overactive.

And the whole phenomena of overactive mast cells  hasn't been recognized until quite recently. Itt turns out that patients  understand that syndrome. A large number of them have mast cell activation syndrome, which is the abundant number of mast cells. Not too many, but rather a normal number of mast cells. But the mast cells are over-producing the chemicals that they produce, and they can produce up to 200 different molecules, and you can get many different kinds of  symptoms  but commonly would be, skin sensitivity, rashes, environmental allergies, GI problems with constipation or diarrhoea.

What’s  commonly known as irritable bowel syndrome, asthmatic like problems or rapid heartbeat, a rapid heartbeat when you're getting up quickly called POTS, postural orthostatic tachycardia syndrome, or sometimes orthostatic hypertension, migraine headaches. So we see these kinds of  symptoms and the mast cells also activate the microglia. 

So in terms of my practice, you know, getting back to ultra-low-dose naltrexone, that I would say almost all the patients I see I put on two ultra-low dose naltrexone. It takes a while to titrate up because we know that the dose to 4.5 milligrams for some patients is a total overdose and they will not be able to tolerate that. And this was actually taught to me by Dr Franco, my friend. So we start at 0.1 milligrams per day, and we go up by 0.1 milligrams every other day, in divided doses.. So it's not one dose at night, but rather four times a day dosing. So it would be 0.1 then three days on the third day, it will be 0.1 twice a day. On the fifth day or sixth day, it will be 0.13 times a day. Then a couple of days after that 0.14 times a day and then start again from the 0.1 so it would be the point to 0.1 0.1 0.1 then 0.2 0.2 0.1 0.1 and going up like that until we get to the maximum of somewhere between five and six milligrams a day as a maximum dose.

So we have some patients whose total daily dose is 0.15 milligrams a day. Total daily dose, and we have other patients where the total dose is six milligrams a day. So what's the dose for ultra-low-dose naltrexone? There is no dose. It's completely idiosyncratic, meaning each patient has their dose, whatever that may be. And so. I didn't stop talking for a long time.

Linda Elsegood: That is absolutely amazing, and you have wrapped it up in 30 minutes. We're going to have to have you come back and talk to us again because I'm sure you  just got started in that 30 minutes. So I'd like to say thank you very much for having joined us today. I really do appreciate it. 

Norman Marcus M.D. My pleasure.

Linda Elsegood: This show is sponsored by Dixon's Chemist, who are the experts in LDN at associated treatments in the UK. Dixon's Chemist, the most cost-effective for LDN in all forms within the UK and Europe. You are maintaining safety standards in  excess of what is required. Why would you choose to get your LDN from anywhere else?

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