Inflammation – Neuro and Otherwise
Inflammation has become an increasingly important topic in fibromyalgia. It’s clear that “central sensitization” – an increase in pain sensitivity engineered by the central nervous system – is present in fibromyalgia (and other chronic pain disorders). That central sensitization could be caused by an inflammatory process which produces pro-inflammatory nerve factors that send the pain-producing nerves into a tizzy.
Neuroinflammation then is a major possibility in FM, but measuring it hasn’t been easy. Only recently have brain imaging techniques been developed that might be able to measure the neuroinflammation that’s present in FM. This study tried to get at the question of neuroinflammation in a different way.
Most studies restrict themselves to either the brain or the body, but this Swedish and Norwegian study did two things that were unusual. Instead of looking for a few cytokines or chemokines, it assessed the abundance of a very large (n=92) number of inflammation-related proteins, and it did so in both the spinal fluid and the blood.
Given how difficult it is to get spinal fluid, the study was a pretty large one involving 40 FM patients and 11 healthy controls.
Pain Res. 2017; 10: 515–525. Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. Emmanuel Bäckryd,1,* Lars Tanum,2,* Anne-Li Lind,3 Anders Larsson,4 and Torsten Gordh3. Published online 2017 Mar 3. doi: 10.2147/JPR.S128508
If FM is, at least in part, an inflammatory disorder, the FM patients should have more inflammatory proteins than the healthy controls. Given the evidence of central sensitization, one might have thought that inflammation would be more likely found in the cerebral spinal fluid, but in the end those signs showed up in the blood as well. This study suggested that both nervous system and systemic (body-wide) inflammation is present in FM – and interestingly enough – have some similarities.
The list of inflammatory proteins increased in FM was not a small one. Instead of cytokines, it was dominated by chemokines belonging to two groups: CC or CL chemokines. Produced by glial cells and neurons in response to injury, these types of cells trigger the release of cytokines. An important pro-inflammatory cytokine called IL-8 which has been found in FM spinal fluid studies was present as well.
One of the chemokines found elevated in fibromyalgia called fractalkine (CX3CL1) may, researchers believe, be the key player in the production of chronic pain. A recent review suggested it was the central nerve factor involved in turning on the microglia. In fact, one animal study was able to prevent the development of pain sensitivity and allodynia by eliminating a factor called cathepsin G which triggers the production of fractalkine. Inhibiting the production of cathepsin is a possible novel therapeutic approach to pain.
If fractalkine is as big as deal in FM as the authors of this article believe, FM patients might be in for some good news at some point. Several fractalkine inhibiting drugs are in clinical trials. According to one report, blocking fractalkine signaling significantly reduced the severity of Crohn’s disease and rheumatoid arthritis. Encouragingly, the drug worked in patients who hadn’t responded to autoimmune drugs in the past.
Again encouragingly, the authors noted that similar immune proteins were found in people with FM and those experiencing chronic back pain after disc herniation. Why one person recovers from a herniated disc while others remain in pain is unclear, but these two studies suggest that the ongoing presence of immune mediators may play a key role. They suggest that a core inflammatory process may be behind many chronic pain states.
This study’s conclusions were exciting because while neuroinflammation has long been suspected in fibromyalgia, finding evidence of it has been difficult. One problem has been that it’s simply not easy to detect the low levels of inflammation believed to be present.
That’s starting to change and we should be able to look forward over the next couple of years to more and more studies assessing this possibly vital component of FM. The presence of increased levels of inflammatory proteins in the cerebral spinal fluid bathing the brain in this study suggests that inflammation is indeed present in the brains of FM patients.
Why the inflammation is present is, of course, a whole other question. A breakdown in the blood-brain barrier, a pathogen in the brain, blood flow issues, or even an immune response in the body could cause an inflammatory response to occur in the brain. The increased levels of inflammation in the blood found in this study suggest that infection in the body could contribute as well. It would do this by sending messages zinging up to the vagus nerve to the brain which trigger microglial cells to produce fatigue and pain symptoms.
Linda Dobberstein, a chiropracter and clinical nutritionist, believes that a “sick brain” that’s pounding out stress signals to the body may be causing most of the problems in FM including gut issues, lactic acid production, sympathetic nervous system activation, hormones and lymphatic congestion. Dealing with these peripheral issues does help, but the brain is the real problem and until that is addressed she believes most of the symptoms associated with FM will remain.
In a recent blog Dobberstein presented evidence suggesting that carb-lovers with FM might want to cut back. A 2016 study found a high fructose diet resulted in the production of high levels of fractalkine in mice and neuroinflammation in their hippocampus and hypothalamus. If that’s so it’s possible that high-carbohydrate diets could affect memory, learning and produce fatigue and many other symptoms. Given that most anti-inflammatory diets do restrict sugars and carbs, a high carb-neuroinflammation connection might not be surprising. (Adding curcumin, interestingly, reduced the inflammation in the mice.)
Dobberstein is not a fan of the FDA approved drugs in FM, and suggested a number of ways to fight the inflammation. (For those who can handle it, Savella does appear to reduce neuroinflammation). Taking magnesium can reduce IL-8. Chondroitin, glucosamine,hyaluronic acid and boswellia serrata may be able to quench several inflammatory chemokines such as IL-8. Omega-3 fish oil and DHA may be able to regulate glial cell activity, and antioxidants such as Grape seed extract, cordyceps, and curcumin (with bioperine) and CoQ10 can help calm the microgila as well.
- Check out some way to naturally reduce inflammation here
Dr. Ginerva Liptan suggests that low dose naltrexone, tumeric, green tea and cannabis may help. The antioxidant and anti-inflammatory properties of tumeric are being studied in Alzheimer’s. Dr. Younger is currently testing a wide range of herbal products to see if they reduce neuroinflamation in people with Gulf War Syndrome. Given Shungu’s recent finding (unpublished) that N-acetyl-cysteine (NAC) increased brain glutathione levels and reduced brain lactate levels in ME/CS patients, it may be another possibility.
It’s good to see objective evidence of inflammation show up in FM, both in the spinal fluid and the blood. It’s even better to see factors that are associated with chronic pain and even memory issues in other diseases such as fractalkine show up in fibromyalgia. If a factor such as fractalkine shows up in enough diseases (it’s been found in FM, Alzheimer’s, diabetes, Crohn’s disease, etc.) drugs will be developed for it. At least two fractalkine drugs are in the early stages of testing. Hooking onto other disease findings and their treatments may in the end be an important factor in finding relief from FM.
For more on neuroinflammation in fibromyalgia see:
- Genes May Be Causing Neuroinflammation and Pain in Fibromyalgia
- The Brain Game: The Search for Neuroinflammation in ME/CFS and Fibromyalgia
- Fibromyalgia – Neuroinflammatory Disease? Savella – Anti-inflammatory?
- The Neuroinflammation Man: Jarred Younger on Inflammation
- Low Dose Naltrexone, Inflammation and Pain: A Different Approach to Fibromyalgia
- Microglial Inhibiting Drugs and Botanicals to Combat Neuroinflammation