This article is not intended to be medical or healthcare advice. Before starting any health related regimen you should seek the advice of your Primary Care Physician or an M.D.
I see CCI in folks with long standing chronic illnesses like ME CFS, Long Haul, Traumatic Brain Injuries, and even 'just' neck related whiplash injuries.
In chronic illness cases, I believe it stems from long standing un - resolved oxidative stress, where the body breaks down connective tissues for collagen that consists of the amino acids Proline and Glycine primarily. Proline is synthesized in the body primarily from glutamate which is NAD/NADPH and ATP dependent from the krebs cycle and glial cell activity. The enzymes ALDH18A1, PYCR1, PYCR2 are involved in the synthesis of proline from glutamate. Ron Davis, a well known ME CFS researcher at Stanford, has reported that in ME CFS patients of his with CCI, that they had very elevated levels of hydroxy proline (oxidized proline from the breakdown of connective tissue likely). It is not new news that these folks also suffer from krebs cycle impairments and low NAD levels.
Glycine is one of the 3 amino acids needed to synthesize glutathione, a key anti oxidant used to process the radical, hydrogen peroxide. Glycine is most often found in the diet in collagen based products and supplements. It can be synthesized from the essential amino acid L-Threonine requiring NAD and or B6, and the conditionally essential amino acid L-Serine requiring folate. A simple amino acid panel can reveal what broad amino acid imbalances exist within the body. The most common cofactor needed to convert the 9 essential amino acids into conditionally essential amino acids is B6. B6 is one of the most common nutritional deficiencies I see in those with long standing chronic illness, it is also one of the most common cofactors for enzymatic reactions in the body not far behind Magnesium and NAD. B6 is critical for synthesizing gaba from glutamate, for the transulfuration pathway, for gut motility, for heme synthesis, etc.
For those folks who have suffered physical neck or head injuries, it should be noted that the shear force from impact or de-acceleration require to tear ligament tissues is less than that required to tear neuronal tissue in the brain. In other words, if you have a head impact severe enough to cause a concussion, its severe enough to tear the ligaments in your neck.
It has been well reported for decades, in the case of ME CFS, that high levels of oxidative stress exist in these folks. It has also been well reported, that the origin of the escalated oxidative stress has been linked to the body's response to a bacterial or viral infection, which drives a response from immune pathways that create reactive oxygen species to kill bacterial and or viral pathogens. Almost all of these pathways use NAD as a cofactor, along with other nutrients. There is direct connection from the cytokines IL-6, TNFA, NFKB to NADPH Oxidase to the KIT genes and mast cell activation. There is no secret why these folks are fatigued, inflamed, and have mast cell activation issues. It should be no secret why symptomatically this is also commonly seen in Long Haul. It has also been well reported for decades that most folks with ME CFS report symptomatic improvement with the addition of anti oxidant therapies. However, in the case of heme pathway issues and or porphyria , there will be a worsening of symptoms on most anti oxidant therapies given the increased demand for heme if anti oxidant enzymes are stimulated.
The Centeno Schultz Clinic, with locations in Colorado, Boston, and the Cayman Islands has been a pioneer in the treatment of various connective tissue injury rehabilitation. This includes ligament and cartlidge damage from sports injuries, and traumatic injuries from accidents like car wrecks, etc. The therapies they use have include anti inflammatory agents like curcumin, fish oil, steroids, but moreso prolo-therapies (platelet rich plasma based therapies), and stem cell therapies to repair soft tissue, regenerate muscle growth, and reduce inflammation. Regarding ligament repair, they use a special sucrose based solution that can cause a reaction in the ligament structure and 'shrink' the length of the torn or stretched ligament. This can result in a 'tightening' of the ligaments, and the improvement in instability conditions in the neck and other vertebrae systems like the lower back and lower lumbar joints commonly compromised in sports injuries. There are many other clinics that offer therapies of similar variety, Centeno Schultz may be the most well known, especially in the professional athletic community. Commonly today, professional baseball pitchers will seek prolo-therapy before under going ligament replacement surgery given the improvement in techniques and outcomes over the last decade. Centeno Schultz has pioneered a procedure specifically for compromised stability in the CO-C1-C2-C3-C4-C5 joints in the upper cervical area of the neck. They assess where the problem is located with a physical evaluation and will use imaging from DMX (Digital Motion X-Rays) and MRI's designed to objectively evaluate the looseness and instability in the joints and ligaments. The procedure, usually involves two basic approaches - either through the back of the throat, and or the sides of the throat, and involves injections into the ligaments to 'shrink' them and or the facet joints to improve mobility, improve disc capacity, and reduce inflammation. Almost none of these procedures are covered by insurance, and almost all are termed, 'experimental', so proceed knowing this.
Physical rehabilitation can also be effective alone or with the above soft tissues procedures. This can involve very minor and specialized upper cervical chiropractor adjustment therapy (e.g. atlas orthogonal practitioners). Neck recurvature therapies to take the load off your discs in your neck and provide more range of motion are also often used for these conditions. Coincidental with CCI are often nerve related issues, baseball pitchers again, often termed thoracic outlet syndrome, and techniques like nerve flossing, dry needling, can be effective to help resolve these issues.
Symptomatically, excess neuro activation, sight and sound over stimulation, poor blood flow to the brain (cognition issues), neck pain, headaches, and poor vagus nerve function are also cited along with excessive sympathetic nervous system activation. The vagus nerve runs right by these sets of upper cervical neck joints, and is often pinched and compromised in these conditions. There are many vagal nerve stimulation devices available each with their own supporters. Vagal nerve function is also supported by some basic nutrients like B1, Alpha GPC (a form of choline), acetyl l carnitine, huperzia, and nicotene. Other therapies like sweedish bitter herbs, and colonics will activate the vagus nerve as well.
Once physical rehab has begun, additive therapies like those proposed in the excellent book, Accessing the Healing Power of the Vagus Nerve, by Stanley Rosenburg have provided relief for many.
There are of course, many factors involved in vagal tone, and vagal nerve functioning, including infections, low blood oxygen levels that lead to activation of the sympathetic branch of the nervous system, emotional trauma and PTSD, olfactory injuries from toxic chemical exposures, etc. With this understanding we can see why some of the brain retraining therapies like the Gupta Protocol, and Annie Hoppers Brain Rewiring can also help many progress.
I have had clients who believe they had mold toxicity, sulfur sensitivity, and various gastro intestinal ailments completely resolve after doing very basic atlas orthogonal adjustments so their Vagus nerve could function more effectively and consistently. Finally, the vaunted NMDA receptors, are located, you guessed it, in the back of the brain and upper neck area. I see these as two connected issues, and why many headaches, neural issues can be resolved with physical neck based therapies.