Treatments of interest

Currently, most of the common treatments for CRPS are just symptom management. Nerve blocks, pain medication, nerve stimulators, nerve ablation. These are ultimately just attempts to stop your brain from receiving the pain and inflammation signal that is being sent.

The problem, though, is that if your nervous system is shot, these may not work well enough, and the problem may crop up elsewhere. It seems like CRPS is so systemic to the nervous system itself that local solutions are not enough. As such, I am not particularly interested in localized solutions, and won’t be exploring them unless they do something extra to regulate the entire system (hence my interest in vagus nerve stimulation).

Ketamine infusions

Potential mechanisms: inflammation, neural pathways, trauma

Ketamine is essentially a hallucinogen that is administered intravenously in large doses over the course of several hours, multiple days in a row. It can be a harrowing, wild experience. The recipient is so deeply intoxicated that it is difficult to draw a comparison between this and other conventional medication or common street drug. This is all expected, and the patient is monitored throughout the process. Ketamine infusions commonly impart lasting relief, sometimes putting patients into remission. However, it is not uncommon for patients to need ‘booster’ sessions months or years after the initial treatments.

At lower (though still large) doses, this therapy is used to successfully treat depression. A variation of ketamine, esketamine, was recently patented for use as a nasal spray in treating depression. The way that ketamine works is unclear (you’ll notice this is a common refrain). However, I recently read an article about a study that shows that ketamine appears to encourage nerve cells to form new connections in mice. An earlier study suggests that ketamine may even encourage brain cell regeneration.

Additionally, a recent trial showed that regularly dosing dextromethorphan (DXM for short) post-infusion significantly extended the period of relief. DXM is the active ingredient in cough suppressants like Robitussin.

Hallucinogens have long been known to form new neural pathways in the brain. Because psychedelics provably promote neuroplasticity, and ketamine is a hallucinogen, and neuroplasticity is a fundamental pillar in any multi-pronged approach to treating CRPS, I am also interested in hallucinogens as a whole in being a part of treating CRPS.

Scrambler therapy

Potential mechanisms: neural pathways, vagus nerve

Scrambler therapy is a form of stimulation that purports to ‘scramble’ the pain signal by overriding it with non-pain signals, transmitted by the device, ultimately ‘reseting’ that pain pathway’s behavior. Think of a large and sort of complicated TENS unit, but operating on a different principle. The technology is patented, and doctors must train through the inventor’s program before they can use them. Scrambler therapy is reportedly very successful relative to other CRPS treatments. In one study of nearly 2300 patients, roughly 80% of recipients report a decrease in overall pain of at least 50%. I have also read personal accounts (here's one) of those who have entered remission because of this treatment. A doctor in New Jersey who famously provides this therapy regularly tweets and posts to Facebook about success stories.

The inventor has complained that mainstream medicine is reticent to incorporate his technology, and although this is the cry of many quacks, I hate to admit that I agree with him. It’s hard to look at the numerous studies and conclude that it really is that simple. As with any treatment, it isn’t 100% effective 100% of the time, but the numbers are very impressive. I’ve read an account of doctors who actually tried the device because they wanted to prove that it didn’t work (sorry, I can't find the article anymore! Here's a tonally similar piece), who ended up deciding to incorporate it into their practice because of it’s effectiveness. I am very confident in this therapy at this point.

Low-dose naltrexone

Potential mechanisms: inflammation, neural pathways

Naltrexone is an opiate antagonist, and is typically prescribed as a pharmaceutical means of preventing drug or alcohol use and relapse. It’s been found that low-dose naltrexone has a surprising anti-inflammatory effect, and is prescribed to treat a range of neurological conditions, including multiple sclerosis, Crohn’s, and CRPS. I don't have much to say about this one simply because it's way over my head. Suffice to say it is a well-regarded and relatively popular treatment.

NOTE: Naltrexone as prescribed is actually one of two forms of naltrexone. The other form, dextro-naltrexone, is not FDA approved for human use because it didn’t show any promise as an opioid antagonist. However, the authors of this article suggest that it may also hold promise as an anti-inflammatory, and at varying doses (unlike LDN), given its lack of function as an opioid antagonist. Although dextro-naltrexone is currently unavailable, I like to keep in mind where the science may go, so that I can keep track of these things and potentially come upon them at a later date when they are available.

Ozone therapy

Potential mechanisms: oxygenation circulation, inflammation

Ozone is commonly used in medicine to clean and disinfect, and as such has a long history in treating infection, and assisting in healing. Ozone therapy in this sense describes the method by which blood is withdrawn, ozone gas is infused with the blood outside of the body, and then the blood is passed back into the patient. Alternatively, ozone gas can be injected directly into the patient.

Ozone's use in treating disease spans back over a century. From what I can gather, ozone 'works' because it can initiate an anti-inflammatory response, trigger the release of antioxidants which can reverse damage done by chronic systemic stress, initiate a neuroprotective response, deliver more oxygen through the bloodstream, and improve bloodflow. This checks...a lot of my boxes.

There is, however, very little information on how ozone therapy can benefit CRPS. All that I've found so far is a case report of a young woman who, after undergoing a (staggering) 120 sessions of ozone therapy, entered complete remission. It is worth noting her CRPS was extraordinarily severe: she suffered more than 30 pseudoseizures a day. This may imply that fewer sessions would be needed for less severe cases.

Given the extraordinary crossover between the mechanisms by which ozone therapy works, and this case report, I have a lot of hope for this treatment. The case report also makes the claim that ozone therapy is very inexpensive and easy to do, which is very promising. I'm curious what the pricing is like, given the quantity of sessions.

Vagus nerve stimulation

Potential mechanisms: oxygenation circulation, inflammation, neural pathways, trauma, vagus nerve

Vagus nerve stimulation is the act of applying an electrical current to the vagus nerve, either subcutaneously or transcutaneously. Vagus nerve stimulators appear to be growing increasingly uninvasive as both the technology improves, and the applications for this treatment broaden.

Vagus nerve stimulation is shown to be effective in treating a number of seemingly disparate conditions, from depression, to digestive disorders like irritable bowel syndrome, all the way to epilepsy. It is shown to increase levels of GABA, and improve some brain functions. A case report for a "military field stimulator", which stimulates the vagus nerve through a branch in the outer ear, shows a CRPS patient experiencing 50% to 100% relief while the device was applied, though he ultimately decided to stop using it because it was uncomfortable and kept falling off.

Currently, one vagus nerve stimulator exists which is approved by Medicare for the treatment of CRPS: in the US, it is called Stivax, and in Europe, it's known as Ducest. It's a small battery pack about the size of two quarters, which is taped to the chest, and from which a lead is run up to the ear, where two small, short needles penetrate the thin skin on the cartilage of the ear, which are held in place by medical tape. It sends a series of pulses for twenty minutes, every forty minutes. Patients wear the device for two weeks at a time, for at least three rounds, with anywhere from one to two weeks in between rounds.

I found a doctor who administers this device not too far from where we live. My partner decided to stop using the device after the second round because they had not yet received any apparent benefit, and - wait for it - it was uncomfortable and kept falling off. Having helped them apply it and check if it's "in" or not on a regular basis, I agree. Medical tape is not enough to keep the needles in without constantly worrying they might be pulled free, as they don't penetrate the cartilage - just the extremely thin skin on the surface. In its current state, it is a very finnicky design.

Despite this experience, I have not written off this treatment. It is clearly still early days, and the vagus nerve is very clearly involved in this condition.


Potential mechanisms: inflammation, oxygenation circulation

Hirudotherapy is the medical application of leeches. This one is pretty simple: leeches are applied to the affected area, allowed to collect blood, and are then removed.

The mechanisms of action are interesting. The leech's saliva increases bloodflow by vasodilation and thinning the blood, has a variety of anti-inflammatory and analgesic properties, fights spasms, has antimicrobial functions, fights scarring, and improves healing. The saliva affects the sensory nerves, but weirdly, it also affects the symathetic nervous system. It seems like a medical super serum. I would also guess that leech therapy improves oxygenation and circulation due to the basic process of sucking blood through and out of the area (combined with the same effects that the saliva imparts).

I spoke to someone who administers leeches in my area, and they informed me that they tend to do multiple rounds of leech therapy across several weeks. On the other hand, two case studies I will reference were only one and two rounds.

A Chinese paper was published recently which apparently discusses the successful use of hirudotherapy in treating CRPS. Unfortunately, only the abstract for the paper is available at the moment. However, I did manage to find an American podiatrist who published a collection of hirudotherapy case studies, two of which include CRPS patients (here referred to as 'reflex sympathetic dystrophy', or 'RSD' - an older term for CRPS.) One patient's pain went from an average 8 out of 10 to a sustained 2 to 4 out of 10 nearly three years after the single treatment. The other patient's pain went form a 7 or 8 out of 10 to complete remission after two rounds.

I said elsewhere on this site that I wouldn't entertain localized treatments, but...I don't know what to make of this. These are powerful results. The fact that the leech's saliva affects the sympathetic nervous system makes this especially compelling for me.

Treating for MAP

Potential mechanisms: bacteria

MAP is a bacteria which causes a wasting disease in cattle, but, until recently, was not considered a human pathogen. However, that is not to say that it had not been suspected at all. In 2009, a British scientist published a journal supposing a "doomsday scenario" in which MAP as a human pathogen is ignored, causing a rise in cases of Crohn's disease. MAP is now generally accepted as a possible direct cause of Crohn's, to the point that a MAP vaccine is in development with the purpose of curing Crohn's. So, what does this have to do with CRPS?

There is a case report of two siblings, one of whom had Crohn's, and the other who had CRPS, both of whose symptoms were wholly resolved after completing treatment for a MAP infection with a combination of ultraviolet blood irradiation and antibiotics. Several of their other family members also tested positive for MAP, and their family has a history of susceptibility to mycobacterial infections.

Another study links a genetic defect, coupled with MAP infection, to rheumatoid arthritis, which is a form of arthritis caused by inflammation. The theory is that the genetic defect allows MAP to trigger RA for those who have both.

I also found a case report of a patient who suffered from mood disturbances, neuropathy, and IBS symptoms who, once treated for their detectable MAP infection, was relieved of all symptoms.

Because MAP is associated with rheumatoid arthritis, an inflammation condition, and the case reports of people with disparate inflammatory issues also having their problems resolved once treated for MAP, I think it's worth exploring the possibility that CRPS can, in some cases, be caused by a MAP infection. The issues right now are a total lack of data associating CRPS with MAP, and the difficulty of testing for MAP.

Transcranial magnetic stimulation

Potential mechanisms: neural pathways, trauma

Description coming soon...

Platelet-rich plasma

Potential mechanisms: I don't know!

Description coming soon...

Nitrous oxide

Potential mechanisms: oxygenation circulation, inflammation, neural pathways, trauma

Description coming soon...