Introduction
This is a follow on from previous articles on the subjects of the roles of lack of oxygen to the brain, the neck and breathing problems in Parkinson’s Disease. Here, we focus on the potentially profound role of special chemical sensors in our necks, which most people affected by PD will never have heard of, called “carotid bodies”.
I'm always interested in structures in the neck, because my major symptom remains the tightness/pain/rigidity that I get in my right neck/shoulder whenever the dopamine replacing drugs wear off. Our necks are such a potential "bottle neck” of the flow of fluids, chemical and electrical signals between head and body. Of particular interest to me, since PD involves neurological issues, is anything which affects breathing and hence oxygen, or blood supply, to the head.
The carotid body is a small cluster of chemoreceptor cells, capable of detecting changes in the chemical make up of the arterial blood, which flow through it, including oxygen concentration, carbon dioxide, blood pH, and even blood temperature. A carotid body is located in the fork of the common carotid arteries, which run up along both sides of the neck.
Carotid bodies are affected by, and release, a variety of neurotransmitters, including dopamine. The fact that dopamine is involved should immediately make anyone with PD or other dopamine deficit conditions sit up and take notice!
The carotid body is linked to the Nervous System and brain via branches of the Glossopharyngeal Nerve collectively called the Carotid Sinus Nerves, and by the Sympathetic Nervous System. The Glossopharyngeal Nerve is one the five or so Cranial Nerves which form the Ventral Vagus Complex or Social Engagement system, responsible for anti-inflammation, detoxification and restoration. The Sympathetic Nervous System is responsible for arousal of the body and brain, and for the Fight-or-Flight stress response.
What Do the Carotid Bodies Do?
The following is based on the article “Revelations About Carotid Body Function Through its Pathological Role in Resistant Hypertension“.
The most important function of the carotid bodies is in ensuring adequate oxygenation of the brain, and preventing hypoxia [reduced or insufficient oxygen]. This includes maintenance of cerebral blood flow brought about by increasing systemic arterial pressure, or by altering breathing. With direct input to the brain stem, the carotid bodies provide excitatory signals to neurons that are both powerful and long lasting.
The carotid bodies are profoundly perfused with blood and have many small-diameter blood vessels of the microcirculation, which are linked to the Sympathetic Nervous System.
Stimulation of the carotid body chemoreceptors triggers hyperventilation, an important protective reflex mechanism ensuring blood gas “homeostasis” [a self-regulating process by which biological systems maintain stability while adjusting to changing internal and external conditions].
The activation of the carotid bodies has dual and competing reflex responses. The resultant response depends on the relative strength of the two reflexes and the magnitude of the respiratory need.
The primary reflex is profound bradycardia (Dorsal Vagus Nervous System mediated slowing of the heart) and vasoconstriction (shrinking of the arteries), responses which are associated with the “Tonic Immobilization” and “Flag and Faint” types of Freeze or shutdown stress responses.
The second reflex consists of tachycardia [fast heart beat] and vasodilatation [widening of the blood vessels],mediated by the Sympathetic Nervous System taking over cardiac control from the Ventral Vagus Nervous System. This is associated with the Fight-or-Flight stress response.
The primary response prevails in the following examples: a diving mammal; human face immersion into cold water; sleep apnea; sudden infant death syndrome; and in anesthetised and mechanically ventilated people. The bradycardia is potent, most likely protective in function to reduce cardiac metabolism in order preserve oxygen.
When the stimulus is intense, the second, alerting response is triggered, including the classical behavioural and visceral adjustments associated with Fight-or-Flight.
Dopamine and Carotid Bodies
As a person with Parkinson's Disease, I am always interested whenever dopamine shows up in descriptions of the normal functioning of the body. We are often told that PD is due to specific cells which produce dopamine in a small part of the brain called the Substantia Nigra, having died. However, we are not usually informed that dopamine production and usage is also vital in many other parts of the brain and body too. This is despite the fact that whenever scientists have looked at these other dopaminergic places, including in the gut and in the retina of the eyes, in people with PD, there always appears to be a dearth or underproduction of dopamine there too. It therefore seems that the dopamine shortage problem in PD is not just in a bean sized area of the brain, but is more systemic.
Another reason to pay attention to dopamine producing regions of the body is that the mainstay treatment for PD is large amounts of dopamine replacing drugs, and/or drugs which stimulate the cells that respond to the neurotransmitter as if dopamine was present (agonists). Since these forms of drug therapy are completely non-targeted, the places in the body and brain which also use dopamine, other than the Substantia Nigra, can end up receiving a glut of dopaminergic activating chemicals too, which can disturb their normal operation, leading to side effects.
These dopamine rich carotid bodies are therefore likely to have very direct relevance to PD too. Indeed, in researching them, I found the article "Carotid Body Oxygen Sensing", which revealed the following.
"The carotid body is among the most dopaminergic structures in the body; As the carotid body is a highly dopaminergic organ, it has been used in dopaminergic cell replacement for Parkinson's disease. Additional advantages of the carotid body for cell therapy rely on its survival in hypoxic environments, and because it offers the possibility of autotransplantation in humans. Carotid body cell aggregates have been transplanted with excellent functional recovery in Parkinsonian rats and monkey. In a safety pilot study performed on PD patients, carotid body autotransplantation [into the striatum part of the brain] produced a clear amelioration in some cases. The beneficial effects of carotid body transplants are not only due to the local release of dopamine but also to a trophic [stimulating] action exerted on nigrostriatal dopaminergic neurons "
I’m not sure whatever happened to this idea, but the fact that transplanting cells from the carotid body into the affected brain regions can reduce PD symptoms, points to its relevance.
So what is the role of dopamine in the carotid body? According to the article “Carotid Body Dopaminergic Mechanisms During Acclimatization to Hypoxia”, the main conclusion appears to be that dopamine release is a mechanism by which a reflex activation of a carotid body is downregulated, inhibited and switched off again after the firing off of signals due to a hypoxia event.
The Medulla Part of the Brain
The medulla is a long cone-shaped structure which makes up the part of the brainstem at the top of the spinal cord. It is responsible for autonomic (involuntary) functions ranging from vomiting to sneezing, heart beat, breathing, vomiting, and blood pressure, as well as sleep. It connects the higher levels of the brain to the spinal cord, and is responsible for several functions of the autonomous nervous system which include the control of breathing via signals from the carotid bodies and other chemical sensors in the body.
It is also primarily involved in carrying out the somatic motor function of the muscles of the face, head and neck, as well as for voluntary motor control of the body and limbs. Connections to the somatosensory cortex suggest that the medulla is also responsible for modulating sensory information from the body.
Carotid Body Activation and Parkinson’s Disease
Drawing all of the above together, it is first interesting to note that the motor functions which the medulla controls are the very things that are most obviously offline or downregulated in people with PD, namely the voluntary movement of the face, head and neck, and of the limbs.
Next, consider that activations of the carotid bodies, due to a lack of oxygen to the brain, have very significant influence on the medulla, and that the primary response of the carotid body is to put the body into an oxygen preserving shutdown or frozen state, in which one loses access to voluntary muscle movements through the action on the medulla.
Thirdly, note that it seems sufficient dopamine is required for turning the carotid body activation off again.
Then a simple and elegant, self-consistent explanation emerges, that, in people with idiopathic PD, our carotid bodies have become stuck “on” in the activated state, initially triggered by a lack of oxygen to the brain, but then not having enough dopamine supplies to be able downregulate or switch the activation off again, effectively trapping us in a permanent shutdown state of Freeze or Tonic Immobility.
So what could be the mechanisms by which people with PD may get stuck like this in the first place? Firstly, there needs to be a lack of dopamine in the body. This could be due to disrupted biochemistry and lack of enzymes, such that we can’t make enough dopamine for ourselves from food. Chronic stress can result in such disruptions. It may also be due to addictive behaviours.
A second possibility, is that for some reason, the dopamine producing cells in the carotid body as well in the Substantia Nigra part of the brain also die off. However, the success of the initial trials of the auto-transplantations of carotid body cells into the problem part of the brain for reducing symptoms, described in the article about carotid body oxygen sensing mentioned above, suggests this is not the case.
A much simpler and more straightforward explanation is that, in the years prior to diagnosis, people with PD tend to be living under chronic stress, and are basically running on adrenaline. The first problem of running on adrenaline is that it is not sustainable long term. The second problem is that adrenaline is created from dopamine, and so creating adrenaline in our brain and bodies uses up dopamine supplies. Hence producing too much adrenaline for too much of the time eventually depletes our dopamine stores completely. Unless one addresses the stressful lifestyles that lead to this, the body and brain will continue to try to convert dopamine as soon as it produced into adrenaline, creating the illusion that we have a dopamine deficit disorder.
Next, we need an acute or chronic hypoxic event, which triggers the activation of the carotid body, either via a lack of oxygen itself or via reduced blood flow to the brain. Anecdotally, I know of a person with PD who had very sudden onset of symptoms after climbing a mountain to high altitudes! This hypoxia of the brain could be due to combinations of past acute physical trauma events, stiff or rigid muscles and fascia of the neck, immobility and constrictions in the neck, vascular problems such as thoracic outlet syndrome, low blood pressure, postural issues and chronically dysregulated breathing patterns. All of these are very common in people with PD.
Interestingly, according to the article cited above in regards to carotid bodies and hypertension, chronic stress itself can cause the carotid body to activate. Indeed, they suggest there is a vicious circle in which acute stress sets off the carotid body in order to generate a fight-or-flight response, but the more times the carotid body is set off, the more sensitive to stress and “trigger-happy” it becomes. In other words, a lower level of stress is needed to set it off next time. This is one of those possible feedback loops between stressors and stress responses, which can lead to ingrained patterns of chronic stress.
Indeed, according to the article, repeated stress can actually cause the carotid body to enlarge, and the authors even suggest removal of part of the carotid as a solution to chronic hypertension issues! This connection to an enlarged carotid body, is tantalizing, because there is actually a rare form of carotid body tumour, the symptoms of which include: hoarseness; difficulty swallowing; partial paralysis or numbness in the tongue; weakness or pain in the shoulders; vision changes, or a drooping eyelid; high blood pressure; heart palpitations. All of these are common PD symptoms too.
Unresolved issues with oxygen supply to the brain could potentially be causing the carotid body to be continually firing off danger signals, resulting in Dorsal Vagus activated types of shutdown. If we then don’t create enough dopamine supplies to overcome this, then we can’t turn this response off.
The role that the dopamine supplementing drugs may then be to temporarily provide enough dopaminergic activity in the carotid body to inhibit the signalling and allow the body to function on low oxygen levels, alleviating the shutdown and hence PD symptoms for a while. The carotid bodies then switch back on when the drugs wear off, as the dopamine supplies become depleted again. On the other hand, if the doses become too large, this may result in the over-inhibition of the carotid bodies, under-stimulating the control of the medulla, resulting in the uncontrolled and involuntary flailing movements known as dyskinesia, a side-effect well known to people with PD.
What are the Practical Action Points?
The pragmatic implications of the above are, firstly, that we need to address the dopamine supply shortage, and to reduce chronic stress as much as possible, as this keeps our dopamine levels depleted, So we need to change our lifestyles and outlooks on life. We absolutely cannot run on adrenaline any longer, or be stressful personality types. We need to learn how to relax, and to prioritize sleep. We need to engage in trauma healing. I have made a list of changes which may help in this regard in the FAQ section.
Secondly, we need to address any barriers to oxygenation of the brain, such as attending to, and resolving, any injuries and thoracic outlet syndrome, mobilizing the neck, and then maintaining mobility, reducing rigidity, stiffness, and dystonia in the neck area, improving our posture, and attending to any breathing disorders or dysregulations. I have personally found a fascia decompression self-care modality called Block Therapy very impactful and highly beneficial in this regard.
The ideas above also predict that hyperbaric oxygen treatment should be effective for people with PD.