These are the biological mechanisms that I currently think are involved in CRPS. These inform what kinds of treatments I look for, and I try to use my knowledge on these mechanisms in trying to make sense of case studies, individual stories, or other evolving treatment methods.

Inflammation 💢

This is the most apparent problem with CRPS. The body's inflammation response seems to be activated all the time, which causes physical symptoms like pain, swelling, redness, and hypersensitivity. Some scientists are now positing that mood disturbances like depression and anxiety are themselves manifestations of inflammation. They aren't merely a consequence of being restricted by this disease, or constantly being in pain. They are a product of the inflammation response itself, and they create a feedback loop which perpetuates the inflammation response, exacerbating both pain and mood disturbances.

An apparently recent approach to the inflammation process in neurological disorders is in examining the role that glial cells play in it. Glia are cells which functionally support your nervous system in a variety of important ways, kind of like a network of workers who perform endless maintainance on a structure. Neuroinflammation and neuropathy arises when glia fail to complete their job of responding to a distress signal from an affected area, creating a chronic condition of indefinitely, repeatedly attempting to address the original distress signal.

Treatments for CRPS typically attempt to mitigate the effects of inflammation (pain medication, for example), and some work to minimize the nerve activity that plays a part in it (pregabalin). I'm primarily looking for treatments which reset the body's inflammation response altogether.

Neural pathways 🧠

Learned behavior ‘writes’ stronger pathways in the brain. This is a manifestation of neuroplasticity: the notion that neurons are capable of changing through use or lack thereof. As such, when your brain receives pain signals a thousand times a day, like “your left foot is burning”, those neural pathways become heavily reinforced, and signals pass through them more frequently and more easily.

Using this knowledge, work is being done to explore how to effectively rewire the brain, teaching it that the affected area is not in danger and it does not need to receive pain signals anymore. This is potentially how exposure therapy, mirror therapy, VR, and physical therapy work to benefit the body. This may also be how drugs like ketamine work.

Oxygenation / circulation 🧬

CRPS can have a restrictive effect on affected areas, inflaming them while also decreasing circulation and, therefore, oxygenation. It is believed that the poor "performance” of the nerves in the affected area has a deleterious effect on circulation, or at least that these symptoms are correlated somehow. Some treatments are believed to work because they increase oxygenation to the area, improving the health of the nerve in turn. For example, hyperbaric oxygen therapy (HBOT) has been shown to work on some individuals. HBOT’s medical function is to effectively flood the blood with higher quantities of oxygen, forcing more oxygen to parts of the body that may have been deprived of it. I believe that this is why HBOT is used to treat traumatic brain injuries and hypoxia.

Additionally, vasodilation (the widening of the blood vessels) is often noted as a potential reason these treatments work. If the pathways for blood are enlarged, more blood can flow through them, potentially providing oxygen to areas that need it, healing or otherwise normalizing those areas.

I’ll be frank in saying I don’t understand how oxygenation works in these cases, and it’s worth noting that the journals I’ve read tend to speak in theoretical terms.

That said, the evidence remains: oxygenation and vasodilation appear to do something good. I’m therefore interested in any treatments that explore oxygenation or improving bloodflow.

The gut & bacteria

“The gut” is not a term that I particularly like. It is delightfully vague for those who want to position themselves as a medical authority, but who don’t want to say something so specific they could actually be corrected. That said, what we are talking about here is the holistic (as in “the whole”) concept of the digestive tract. Gut health is increasingly being found to play a role in a variety of seemingly unrelated biological processes, from psychological well-being to the health of our nervous system.

What I find particularly compelling about this association is that vagus nerve stimulation is currently approved for the treatment of a variety of chronic gut conditions. Furthermore, a recent study has shown that your gut’s microbiota (the bacteria that populate your digestive system) serve in the communication of your gut to your vagus nerve.

Many sufferers of CRPS also have chronic gut problems, like UC or IBS. Considering that vagus nerve stimulation is currently approved to treat both of these conditions through the same mechanism (simple, direct stimulation of the vagus nerve), I believe this should absolutely not be overlooked.

Additionally, a new tack I am interested in is the role of bacteria, good and bad, in the wider spectrum of our overall well-being. For awhile now, it has been widely accepted that the microbiota of your gut play a role in your mental health, but it has not been very well understood how that works. The current hypothesis is that gut bacteria play a role in how your nervous system communicates throughout your body. Furthermore, there may be specific bacteria which give you good mental health, and specific bacteria which can cause malladies like inflammation.

For example, the strain mycobacterium vaccae appears to play a significant role in reducing depression and anxiety. Alternatively, mycobacterium avium subspecies paratuberculosis (MAP for short) appears to be connected to severe inflammation conditions, specifically Crohn's and rheumatoid arthritis. Many scientists are deeply invested in the notion that MAP causes Crohn's, to the point that a "Crohn's vaccine" is currently in development based on MAP. Because CRPS is an inflammation condition, I am exploring whether or not MAP may play a role.

Treating gut- and microbiota-related dysfunction may mean treatments that seem very esoteric, like changes in diet, and attempts to rebalance and proliferate healthy microbiota in the gut through the use of things like prebiotics and probiotics.

Trauma 🥀

Trauma often appears to play a role in the likelihood of contracting CRPS, and dealing with that trauma likely plays a role in resolving the condition. Trauma can, in layman’s terms, fry healthy neural pathways and wire up new, negative ones that are more prone to communicating stress responses, like “your limb is in danger!”. An easy and tragic example is the likelihood that someone who experienced trauma will flinch prematurely in otherwise safe environments, or around people they trust.

Treating trauma through therapy, with psychiatric medication, and through the use of psychedelics like ketamine is, I believe, an important part of resolving this condition for people who have a traumatic history.

Vagus nerve 👤

The vagus nerve is a large cranial nerve in the body that play a role in the parasympathetic nervous system. It is present throughout the entire body, and it primarily works to moderate the heart and your internal organs. “Vagal tone”, which is often measured by determining heart rate variability (HRV), theoretically speaks to the “health” of the vagus nerve. People who suffer from stress-related conditions and PTSD can have lower HRV.

There have also been associations made between people who have experienced trauma, people with internal organ malfunction (notably gut issues, like IBS, Crohn’s, and ulcerative colitis), and incidences of CRPS. Anecdotally, this is a common observation I’ve made: I often see that people with CRPS also suffer from other parasympathetic disorders. A CRPS treatment center I contacted asked, unsolicited, if my partner had stomach problems, as this is also common in their experience.

I am personally extrapolating that better vagal tone and higher HRV may play a significant role in treating CRPS. I personally substantiate this position with evidence that vagus nerve stimulation appears to improve CRPS.