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Pradeep Chopra, MD - Chronic Pain (2017 Conference) (LDN, low dose naltrexone)
Management of chronic pain with low dose naltrexone (LDN).
My name is Pradeep Chopra. I'm an assistant professor at the Brown Medical School. I'm also a pain management specialist. This is a standard disclaimer: I have no actual or potential conflict of interest in relation to this presentation or program. The presentation will discuss off-label uses of medications. Discussions in this presentation are for general information purposes only. Please discuss your own particular treatment with your physician. This presentation or discussion is not meant to take place of your doctor. In terms of my disclosure, I'm a pain medicine specialist with a special interest in complex pain conditions. My training was at the Harvard Medical School. I now work as an assistant professor at Brown Medical School in Rhode Island USA. I am on the medical advisory board for The Coalition Against Pediatric Pain. It is a nonprofit organization. I have no other financial disclosure.
Chronic pain is generally described as three types on predominantly. The first type is structural pain, also known as nociceptive pain. The second type is neuropathic pain. And the third type is mixed, which is between nociceptive and neuropathic pain. In this presentation, I plan on discussing one example of each. Each of the following cases is representative of many cases treated with low dose naltrexone. I have been using low dose naltrexone for well over, I would say, about 8 to 10 years now, and we've had some amazing results. What I would like to do is to share with you an example of each of these types of pains. These are typical examples, not anecdotal experience that I have with these pain conditions. There are many, many other examples of these types of pains.
The first example I wanted to pick up is spinal pain and the use of low dose naltrexone. Spinal pain is predominantly a nociceptive pain. Any chronic pain condition has both nociceptive or structural pain, and neuropathic pain or nerve pain. But in this example that I'm going to use, it was predominantly structural pain or nociceptive pain. This was a 56-year-old lady who presented with severe back pain approximately 5 years ago. The pain was across her lower back and radiated down both of her legs. It was a constant pain, and she would have intermittent exacerbations during which she had to basically stop doing anything and sit down or lie down. She was very nonfunctional. She couldn't really go do anything for herself. She was depending on others to help her. She had had three back surgeries, a lumbar discectomy, and two lumbar fusions. None of the surgery really made a significant difference to her pain. When I saw her, she was on gabapentin 600 mg three times a day, ibuprofen 200 mg as needed. And she was on lisinopril for blood pressure, sertraline 40 mg for depression and zolpidem for sleep. She did have severe insomnia, mostly because of her back pain. She had already tried and failed other antidepressants for her pain, especially from the tricyclic group, like amitriptyline and nortriptyline. She had already tried various nonsteroidal anti-inflammatory drugs. She had tried anticonvulsants. She had used a TENS unit. She even had a spinal cord stimulator, which was implanted, which really didn't help her at all. She had tried muscle relaxants, opioids, and lots of physical therapy. None of these had made a significant difference to her pain. She continued to be really nonfunctional. When we saw her, she had an antalgic gait. She had significant tenderness in the lumbar region. We did a lumbar facet joint stress test, and it was positive bilaterally. She had cyclic joint pain, bilaterally. Straight leg raising test was positive on the right, which implies that she had some disc pain. She was unable to walk more than 30 feet, after which she had to rest. And she had absent deep tendon reflexes to the right knee.
So the treatment strategy here was to see if we could take away some of the inflammatory component of her pain. We tried lumbar steroid injections to the transitional facet joints. These are the joints that are above and below the fusion. And she reported mild to moderate relief. We tried cyclic joint injections, and she reported moderate relief. She did not have any relief from lumbar epidural steroid injections, which are usually done for discogenic pain. Overall the injections provided her with moderate relief, but it wasn't consistent. She continued to have disabling pain and was not functional at all.
I started her on low dose naltrexone at 2.5 mg every morning for two weeks. I usually start my patients at half the dose, at 2.5 mg. It's just a personal preference. What I've had in past experiences is that if patients develop a side effect, it really just turns them off from doing the drug in the future, so I try to introduce it slowly. I started her at around 2.5 mg every morning for two weeks. And then after about two weeks, I put her on 4.5 mg of low dose naltrexone, again in the morning. The reason I chose morning is that a lot of these patients have insomnia from low dose naltrexone, so I prefer starting it in the morning and then once they're used to it, I switch them to taking it at night. So after about a month, she was on 4.5 mg of low dose naltrexone at night. In 4 weeks, she was able to walk 100 feet, which is about 3 times what she was walking before. When she had first come to me, she was walking about 30 feet. She was not as tired, and she also had greatly improved cognitive functioning, mostly because the pain wasn't as severe. After about 2 months, she was able to do her own grocery shopping, which is about a process that took about one hour. She was able to cook. She didn't really need any more injections. We held off on that. And by 6 months she was doing significantly well. She was volunteering at her church, a Sunday school. She was looking for a job. Again, she still had baseline pain, but she didn't have as many flare ups. She had more good days than bad days. In terms of her side effects, she had headaches initially, which responded well to acetaminophen. After approximately 2 weeks of taking low dose naltrexone, the headaches resolved.
My next example is that of a severely painful condition known as complex regional pain syndrome. It's predominantly a neuropathic pain condition. It involves nerves. Again, like I explained to you, all chronic pain conditions have both neuropathic pain as well as nociceptive pain; but this case is predominantly a neuropathic pain condition with some joint pain and muscle pain also. Just to give you an idea of what complex regional pain syndrome, or CRPS, Is, it's definitely a nerve pain condition. It usually starts after a trauma. It can start after a simple needle stick injection, or a sprain or after a surgery. it is the most painful condition known to mankind. According to the McGill pain scale, CRPS is rated as pain that is worse than amputation or labor pain. Unfortunately, it is fairly common in the United States at about 20,000 new cases every year. The sad part is that there are really no great drugs that work on it. It's a severe neuropathic pain condition, and they're really not many drugs that work on it. It affects both adults and children. So this is a very typical case of CRPS that I picked.
This is a girl who, when she was 15 years old, had sprained her left foot. She was running in school. She injured her left foot, nothing major. She continued to have severe pain to the left foot despite all sorts of treatments. She had all sorts of testing done: MRIs, EMGs, x-rays. They were all normal. She was diagnosed tentatively to have ligament sprain, and her foot was placed in a cast. Unfortunately, the pain continued to worsen despite the cast. Now that is a classical symptom of CRPS: when the limb is immobilized, they continue to have severe pain. The cast was removed and she was noted to have classical symptoms of CRPS, which includes swelling, pain to touch which is known as allodynia, she had a temperature difference between her left foot and her right foot, she had color difference - her left foot was darker in color, it was bluish in color as compared to the right. She underwent physical therapy. She had spinal injections. She had medications. All with no change. In fact, she started to develop a similar pain in the right lower extremity also.
Because she wasn’t responding to treatments, the hospital thought it might be a psychiatric condition. She was diagnosed with conversion disorder. Her mother, who took her to various doctors for treatment, was accused by the hospital of child neglect because she sought treatment with other doctors. Child protection services were involved and that ended all treatment for her. Her condition continued to worsen, and now she was in a wheelchair because of a CRPS to both her legs.
When I saw her, she was 18 years old. She had had this pain for about three years now. It was excruciating pain to both her legs. She had even attempted suicide once because of her pain, and because of being accused of conversion disorder. She had also started to develop complications of CRPS, including dizziness, palpitations, a condition known as POTS, postural orthostatic tachycardia syndrome. She had some significant atrophy of both her legs. She had dystonia to the left ankle. Because of the severity of the case she was started on low dose intravenous ketamine infusion, and LDN. She started to have a significant response to the low dose intravenous ketamine infusions, and over the next 3 months, the time between the infusions increased, and by about 3 months they were stopped. She continued low dose naltrexone with significant improvement in pain and function. By six months her pain was quite well controlled enough that she could start some low-level physical therapy. Because of the severe atrophy to both her legs she progressed slowly, and the physical therapy was increased as she tolerated it. After a year she was able to walk on her own. She was able to donate her wheelchair to charity. She does continue to have pain, but it is tolerable. She's ambulatory on her own. She's really on no medication, other than low dose naltrexone and propranolol. The propranolol was for the POTS. This is actually her picture on the left before the LDN. As you can see, a dark red foot, and there's dystonia to the foot. And now you can see the right foot again, after she was on LDN for about a year.
The other condition that I wanted to talk to you about was a mixture of nociceptive are structural pain and neuropathic pain. At one time this was considered to be a rare condition, but now it's a fairly common condition called Ehlers Danlos Syndrome (EDS). The reason I chose this condition is because this is a condition that presents with equal severity in terms of structural pain and neuropathic pain.
This is a 22 year old lady who had pain in multiple joints, including her head neck, and shoulders. It had been increasing over the last one year. The pain would increase with weight-bearing, walking. The best relief she would get would be sitting in a recliner. She had a lot of pain also localized to her right knee. When she would walk, she had a popping sensation, which was subluxation and dislocations to her joints in the right lower extremity. She had similar subluxations and dislocations to her shoulders and her hip joint. She also reported dizziness and palpitations, and easy bruising, which are all symptoms of Ehlers Danlos Syndrome. The only medicine that she could tolerate was ibuprofen, which provided her with just moderate relief, but for a very short while. She was a told that she's double jointed. In her past medical history, she had significant, severe growing pains. On physical examination her right knee had a hypermobile patella. She had hyperextension of both her knees. Her skin was smooth and velvety. Her Beighton score was 6 out of 9. These are all symptoms of Ehlers Danlos Syndrome. A Beighton score of 6 out of 9 is considered significant for EDS. She had small scars which were paper-thin and atrophic. The MRI of her joints was normal. These patients usually don't have anything on the MRI because it’s predominantly a condition of subluxation and dislocations, so static pictures really don't demonstrate any difference. In summary, this is a young woman with diffuse body pain to her muscles and joints, with a connective tissue disorder that was both nociceptive and neuropathic in nature. She had tried and failed all sorts of treatments.
When I saw her, I started her on proprioception exercises. These are exercises that are used to develop a joint position sense. She was started on muscle strengthening exercises. These are exercises that were meant to strengthen her muscles. I started her on low dose naltrexone at 4.5 mg, and I did a bracing for her right knee joint, which was severely hyperextended. Approximately 2 weeks later, she was able to stand. She was able to walk up to a block. There was no difference to her pain in the upper and lower back, but she was able to weight bear somewhat, and she was able to walk. In about 4 weeks, she was able to walk up a flight of stairs without stopping. She could be on a treadmill for 30 minutes at low resistance. And in 3 months, she had significantly decreased pain and she was no longer taking any of her medications for pain.
Approximately a year later, she slipped on ice and fell. She fractured her left fibula. She underwent an open reduction and internal fixation. For the surgery, her low dose naltrexone was stopped. She forgot to restart it after the surgery, so she really wasn't on it for about 3 months. She started to notice her general body pain returning. She started to have diffuse body pain, upper back pain, lower back pain, shoulders knees. I restarted her low dose naltrexone and by 2 months she was back to functioning again. She has been on low dose naltrexone for the last two years. Her pain is much better controlled. She does take naproxen occasionally. She's actually graduated from nursing school and holds a full time job.
Dr. Mark Cooper, who's really a brilliant scientist, coined this term “inside-out, stand down therapy”. I find it really unique and I found it really helpful. The idea was that we can extinguish neuroinflammation in a primary afferent using something known as inside out pharmacology, which means that we want to suppress inflammation inside the nerve, as well as we want to suppress any inflammatory mediators outside the nerve. The simplest and most cost effective form of inside-out pain therapy is to use a combination of low dose naltrexone and naproxen, the idea being that the LDN would suppress the neuroinflammation inside while the naproxen would suppress any neuroinflammation outside.
Some of the pain conditions that I have successfully treated with low dose naltrexone are neuropathic pain, muscular pain, tendonitis, headaches and migraines - these are really complex migraine conditions where I have found some good relief. Again, I don't want to give you the impression that all migraines and headaches can be treated with LDN, but we've had fairly decent success. LDN is a drug that's worth trying. It has a very low side effect profile. It is a very inexpensive drug. And again, it's not a magical drug that'll help everyone, but it does help in a lot of cases. I have not had much success with trigeminal neuralgia and postherpetic neuralgia.
Thank you again. Thank you very much to the LDN Research Trust for hosting this conference. I am happy to answer any questions. My email address is on this last slide.
Keywords: low dose naltrexone, LDN, pain, nociceptive pain, neuropathic pain, spinal pain, complex regional pain syndrome, CRPS, postural orthostatic tachycardia syndrome, POTS, Ehlers Danlos Syndrome, EDS, headaches, migraines, trigeminal neuralgia, postherpetic neuralgia