Post by Lady~RavenHeart on Aug 28, 2005 14:18:40 GMT 2
The cause of fibromyalgia remains elusive, mainly because there are no physical examination or laboratory findings suggestive of a specific diagnosis. Further, muscle biopsies taken from the tender points of fibromyalgia sufferers are inconclusive for any tissue abnormalities specific to fibromyalgia. However, researchers have several theories about causes or triggers of the disorder. A few examples would be an infection, a car accident, and the presence of rheumatoid arthritis, lupus or hypothyroidism. These injuries may affect the central nervous system. Fibromyalgia may be associated with changes in muscle metabolism, such as decreased blood flow, causing fatigue and decreased strength. Others believe that fibromyalgia is triggered by an infectious agent such as a virus in susceptible people, but no such agent has been identified. Even if these things don’t necessarily cause fibromyalgia, they may cause changes in your body that can predispose you to a developing fibromyalgia.
Since it is believed that there isn’t one single cause of fibromyalgia, a number of factors must contribute. These factors may include:
Autonomic Nervous System Dysfunction
The autonomic nervous system is the portion of the nervous system that controls the function of the different organs and systems of the body. For instance, it regulates body temperature, blood pressure, heartbeat rate, and bowel and bladder tone. It is called autonomic because it is something that our body does automatically since we don’t consciously control these things. The autonomic nervous system works closely with our hormonal system and neurotransmitter system and it is particularly involved with something referred to as the hypothalamic-pituitary-adrenal axis.
The autonomic system is divided into two branches: sympathetic and parasympathetic. The sympathetic system prepares in response to stress or emergencies while the parasympathetic system favours digestive functions and sleep. The action of these two branches of the autonomic nervous system is by something called neurotransmitters and hormones. Dysfunction in the autonomic nervous system is manifested in abnormalities in the levels of neurotransmitters, hormones and abnormal action of the hypothalamic-pituitary-adrenal axis. These are discussed further.
Neurotransmitters
Neurotransmitters are the substances that nerves in the autonomic nervous system use to communicate with each other. They are the vehicles that carry information back and forth between your body and mind. Certain neurotransmitters such as serotonin, substance P, and beta-endorphins have all been studied looking for causation.
· Substance P
Several different studies have shown that substance P – a neurotransmitter that causes pain to be felt – is elevated threefold in the spinal fluid of patients with fibromyalgia. Substance P is composed of 11 amino acids and elevation of this neurotransmitter leads to an enhanced pain perception. Thus, for the same painful stimulus, a person with higher levels of substance P will feel more pain than another person.
· Endorphins
Recent studies have looked at the neurotransmitter beta-endorphin in the immune cells of patients with fibromyalgia. Beta-endorphin is the opioid produced by the body to fight pain. It is also involved in stress responses, pain suppression, and mood disorders. Interestingly, high beta-endorphin levels in the brain suppress the immune system. One study found that the beta-endorphin levels of fibromyalgia patients is close to half that of the healthy population. Therefore, in the future, beta-endorphin levels may be used as a diagnostic tool or to monitor treatment of patients with fibromyalgia.
· Serotonin
Some studies suggest that fibromyalgia sufferers may have decreased levels of the neurotransmitter serotonin which is linked to depression, migraines and gastrointestinal distress. Most antidepressant medications raise levels of serotonin explaining low doses of these drugs help some patients with FMS (see section below on Treatments for Fibromyalgia for more information on antidepressants as a treatment for fibromyalgia).
· Neurotransmitters and Medications
When taking medications for fibromyalgia it is important to discuss with your health care provider whether the medications will alter neurotransmitter levels. In some instances, drugs prescribed for fibromyalgia can actually alter the neurotransmitter levels even more, worsening your condition.
Hormones
· Cortisol
Hormones have also been studied in order to uncover if any abnormalities exist in the levels of various hormones of fibromyalgia patients. Two specific hormones that have been shown to be abnormal are cortisol and growth hormone. Cortisol is released by the body in times of stress, both physical and mental. It can partially explain why fibromyalgia patients feel constantly “off” or “drained”.
· Growth Hormone
With growth hormone the problem seems to be underproduction. Normally, during exercise and during sleep the body is supposed to produce a several fold increase in the production of growth hormone. In fibromyalgia, the autonomic nervous system responsible for the release of growth hormone is under-responsive and the required increase in the hormone is not seen. Growth hormone has a powerful effect on the connective tissues in your body. It directly stimulates vital cellular products such as fibroblasts, mast cells, ground substance and collagen fibres. It is important in wound healing because it is the rapid production of collagen fibres by fibroblasts that is necessary for repair. Growth hormone is normally released during deep levels of sleep but people who suffer from fibromyalgia have this level of sleep disrupted and therefore have very low levels of growth hormone. This can lead to a decreased repair response, decreased immune response and fibromyalgia symptomatology.
· Norepinephrine
Norepinephrine is a hormone that is released by a part of your autonomic nervous system known as the sympathetic system. By releasing this hormone and controlling the release of epinephrine via the adrenal gland, the sympathetic nervous system is able to control your bodily functions that aren’t under conscious control: heart rate, blood vessel contraction, sweating, salivary flow, intestinal movements, and even the little hairs on your arms. As with growth hormone, fibromyalgia patients seem to suffer with reduced levels of epinephrine responses, especially in response to low sugar levels or exercise. Abnormal levels of norepinephrine will cause symptoms to be felt all over your body. These symptoms may manifest as the chronic fatigue and pain associated with fibromyalgia.
Hypothalamic-Pituitary-Adrenal Stress Axis
Recent studies have shown that this axis that lies in the brain may have a role in the development of fibromyalgia syndrome. Among other things, the hypothalamic-pituitary-adrenal axis (HPA) is the part of your brain that deals with how your body handles stress, both physical stress and psychological stress. Many patients with fibromyalgia report the onset of their symptoms after a significant period of emotional stress or a specific traumatic event. Fibromyalgia sufferers also report a higher level of daily stress and that their symptoms are significantly aggravated by stress. This points to over-activation of the HPA axis as a possible cause of fibromyalgia. Actually, most of the symptoms associated with fibromyalgia, such as sleep disorder, headache, and irritable bowel can be traced back to increased activity of the HPA axis. Curiously, studies have shown that the main stress hormone that is secreted in the HPA axis in response to stress – cortisol – is lower than normal. Therefore whether it is overactivity or underactivitiy of the HPA axis is not entirely clear. What is clear is that there is an alteration in the HPA axis and more research is required to identify the precise nature of this alteration.
Sleep Disturbances
Some researchers theorize that the sleep disorders seen with fibromyalgia may actually be a cause, as opposed to symptom – of the syndrome. Stage 4 sleep is the deepest level of sleep and is the one that is most lacking in fibromyalgia sufferers. Evidence that sleep disturbance may be a possible of fibromyalgia was given by a study that was able to induce fibromyalgia-like symptoms in normal volunteers by depriving them of deep sleep.
It is during stage 4 sleep that a hormone called somatomedin C is released into the system. Without enough deep sleep, fibromyalgia sufferers show abnormally low levels of this hormone which is essential for the body to rebuild itself. Lack of this hormone may be causing the characteristic muscle pain and fatigue commonly seen in fibromyalgia. Also, release of growth hormone occurs primarily during stage 3 and stage 4 of non-REM sleep. Thus disturbed sleep will affect the release of this hormone causing abnormalities in your body. One third of patients with fibromyalgia have low insulin growth factor (IGF) levels, an indication of low growth hormone secretion. Interestingly, amongst fibromyalgia sufferers, the severity of the sleep disorder seems to correlate with the number of tender points they have (see below for an explanation on tender points).
Sleep deprivation is also known to cause some of the symptoms involved with “fibrofog.” People who lack enough sleep or poor deep sleep have been known to experience feelings of being in a fog, loss of control of though processes and poor memory.
Studies have shown that exercise increases the amount of time spent in deep sleep. Thus, it is not surprising that exercise has been confirmed to be of value in the treatment of fibromyalgia. See the section on Treatments for more information on appropriate exercise regimens.
Injury or Microtrauma to Muscles
It has been suggested that the pain of fibromyalgia may be related to microtrauma in deconditioned muscles and that exercise helps fibromyalgia sufferers by conditioning these muscles. For example, pain in the muscle causes spasm in the muscle, causing more pain, which in turn causes more spasm. The muscle becomes chronically congested, and the delivery of oxygen and other nutrients, as well as the removal of metabolic wastes and acids, becomes impaired.
A recent study looked at the relationship between neck injuries and the onset of fibromyalgia. It found that fibromyalgia was 13 times more likely to occur following a neck injury than an injury to the lower bodies.
However, muscle biopsies have not been able to identify any difference in sore muscles when compared to other non-tender parts of the body. Also, some tender points are not over muscles or tendons but over bones or fat pads. Scans of fibromyalgic muscle tissue by electron microscope have revealed some abnormalities in the levels of a muscle sugar called glycogen. Abnormal organelles called mitochondria that are involved in energy production have also been found in fibromyalgia patients. So while there is some evidence that abnormalities in the metabolic properties of the muscles may be involved in fibromyalgia, it is more probable that these injuries to muscles don’t cause fibromyalgia, but rather, they may awaken a hidden genetic predisposition.
Another way whereby injuries may be involved with fibromyalgia is that an injury to the upper spinal region may affect the central nervous system and may trigger the development of fibromyalgia in some people. The brain is easily overwhelmed by head injury, viruses, and severe stress. When an injury to the brain occurs, it triggers a cascade of biological events involving neurotransmitters, hormones and changes in blood flow, to protect the traumatized area. Unfortunately for the patient, such defensive action by the brain can cause serious problems in the body. Some of the things that they can cause are many of the same symptoms that fibromyalgia patients may be suffering from. Several studies are currently analyzing brain wave activity to see if there are differences between normal people and fibromyalgia sufferers.
Other Possible Causes
Other less frequently theorized causes include:
Central nervous system dysfunction. Some believe that fibromyalgia sufferers have an abnormal nervous system that leads to abnormal processing of sensory stimuli. This means that the patient’s nervous system processes normally non-painful sensory stimuli as being painful. This phenomenon in which pain results from a stimulus that should not normally be painful is known as allodynia.
Changes in muscle metabolism, such as decreased blood flow, causing fatigue and decreased strength.
Infectious agents such as a virus but no such agent has been identified. Also, if fibromyalgia were infectious we would expect so see an increased incidence in spouses of an affected patient and this is not the case.
Immune system abnormalities. Several changes in immune system function have been found in fibromyalgia, generally in the direction of increased activity. Hyperactive immune system symptoms can be induced in normal volunteers through sleep deprivation. This may link sleep dysfunction and immune function as causative agents in fibromyalgia.
Muscle tension. Muscles that are in a chronic state of contraction will not relax fully, even with rest. Muscles constantly taxed this way can produce an unlimited variety of unpleasant symptoms. It should also be noted that contracted muscles not only cause the brain to release certain chemicals that can cause pain, but that they greatly restrict the oxygen that they take in, which can produce drastic side effects since oxygen is responsible for regulating the fluid levels in soft tissues as well as repairing injuries.
Tense muscles can also press adjacent nerves, causing pain, tingling and numbness. Stressed nerves can create weakness in affected muscles and restrict motion in nearby joints. A muscle’s constant state of contraction will cause it to shorten, limiting motion and causing muscle aches and stiffness.
Genetic predisposition. Although no specific inheritance pattern has been identified, an increased incidence in relatives of affected patients had been noted. Therefore, development of fibromyalgia may involve certain predisposing factors that are inherited, as well as precipitating factors such as trauma, infection, stress or sleep disruption. Current studies on twins with fibromyalgia are examining the possibility of genetic predisposition to the syndrome.
Current research is looking that the significance of spinal stenosis (narrowing of the spinal canal) or Chiari malformations and fibromyalgia.
Since it is believed that there isn’t one single cause of fibromyalgia, a number of factors must contribute. These factors may include:
Autonomic Nervous System Dysfunction
The autonomic nervous system is the portion of the nervous system that controls the function of the different organs and systems of the body. For instance, it regulates body temperature, blood pressure, heartbeat rate, and bowel and bladder tone. It is called autonomic because it is something that our body does automatically since we don’t consciously control these things. The autonomic nervous system works closely with our hormonal system and neurotransmitter system and it is particularly involved with something referred to as the hypothalamic-pituitary-adrenal axis.
The autonomic system is divided into two branches: sympathetic and parasympathetic. The sympathetic system prepares in response to stress or emergencies while the parasympathetic system favours digestive functions and sleep. The action of these two branches of the autonomic nervous system is by something called neurotransmitters and hormones. Dysfunction in the autonomic nervous system is manifested in abnormalities in the levels of neurotransmitters, hormones and abnormal action of the hypothalamic-pituitary-adrenal axis. These are discussed further.
Neurotransmitters
Neurotransmitters are the substances that nerves in the autonomic nervous system use to communicate with each other. They are the vehicles that carry information back and forth between your body and mind. Certain neurotransmitters such as serotonin, substance P, and beta-endorphins have all been studied looking for causation.
· Substance P
Several different studies have shown that substance P – a neurotransmitter that causes pain to be felt – is elevated threefold in the spinal fluid of patients with fibromyalgia. Substance P is composed of 11 amino acids and elevation of this neurotransmitter leads to an enhanced pain perception. Thus, for the same painful stimulus, a person with higher levels of substance P will feel more pain than another person.
· Endorphins
Recent studies have looked at the neurotransmitter beta-endorphin in the immune cells of patients with fibromyalgia. Beta-endorphin is the opioid produced by the body to fight pain. It is also involved in stress responses, pain suppression, and mood disorders. Interestingly, high beta-endorphin levels in the brain suppress the immune system. One study found that the beta-endorphin levels of fibromyalgia patients is close to half that of the healthy population. Therefore, in the future, beta-endorphin levels may be used as a diagnostic tool or to monitor treatment of patients with fibromyalgia.
· Serotonin
Some studies suggest that fibromyalgia sufferers may have decreased levels of the neurotransmitter serotonin which is linked to depression, migraines and gastrointestinal distress. Most antidepressant medications raise levels of serotonin explaining low doses of these drugs help some patients with FMS (see section below on Treatments for Fibromyalgia for more information on antidepressants as a treatment for fibromyalgia).
· Neurotransmitters and Medications
When taking medications for fibromyalgia it is important to discuss with your health care provider whether the medications will alter neurotransmitter levels. In some instances, drugs prescribed for fibromyalgia can actually alter the neurotransmitter levels even more, worsening your condition.
Hormones
· Cortisol
Hormones have also been studied in order to uncover if any abnormalities exist in the levels of various hormones of fibromyalgia patients. Two specific hormones that have been shown to be abnormal are cortisol and growth hormone. Cortisol is released by the body in times of stress, both physical and mental. It can partially explain why fibromyalgia patients feel constantly “off” or “drained”.
· Growth Hormone
With growth hormone the problem seems to be underproduction. Normally, during exercise and during sleep the body is supposed to produce a several fold increase in the production of growth hormone. In fibromyalgia, the autonomic nervous system responsible for the release of growth hormone is under-responsive and the required increase in the hormone is not seen. Growth hormone has a powerful effect on the connective tissues in your body. It directly stimulates vital cellular products such as fibroblasts, mast cells, ground substance and collagen fibres. It is important in wound healing because it is the rapid production of collagen fibres by fibroblasts that is necessary for repair. Growth hormone is normally released during deep levels of sleep but people who suffer from fibromyalgia have this level of sleep disrupted and therefore have very low levels of growth hormone. This can lead to a decreased repair response, decreased immune response and fibromyalgia symptomatology.
· Norepinephrine
Norepinephrine is a hormone that is released by a part of your autonomic nervous system known as the sympathetic system. By releasing this hormone and controlling the release of epinephrine via the adrenal gland, the sympathetic nervous system is able to control your bodily functions that aren’t under conscious control: heart rate, blood vessel contraction, sweating, salivary flow, intestinal movements, and even the little hairs on your arms. As with growth hormone, fibromyalgia patients seem to suffer with reduced levels of epinephrine responses, especially in response to low sugar levels or exercise. Abnormal levels of norepinephrine will cause symptoms to be felt all over your body. These symptoms may manifest as the chronic fatigue and pain associated with fibromyalgia.
Hypothalamic-Pituitary-Adrenal Stress Axis
Recent studies have shown that this axis that lies in the brain may have a role in the development of fibromyalgia syndrome. Among other things, the hypothalamic-pituitary-adrenal axis (HPA) is the part of your brain that deals with how your body handles stress, both physical stress and psychological stress. Many patients with fibromyalgia report the onset of their symptoms after a significant period of emotional stress or a specific traumatic event. Fibromyalgia sufferers also report a higher level of daily stress and that their symptoms are significantly aggravated by stress. This points to over-activation of the HPA axis as a possible cause of fibromyalgia. Actually, most of the symptoms associated with fibromyalgia, such as sleep disorder, headache, and irritable bowel can be traced back to increased activity of the HPA axis. Curiously, studies have shown that the main stress hormone that is secreted in the HPA axis in response to stress – cortisol – is lower than normal. Therefore whether it is overactivity or underactivitiy of the HPA axis is not entirely clear. What is clear is that there is an alteration in the HPA axis and more research is required to identify the precise nature of this alteration.
Sleep Disturbances
Some researchers theorize that the sleep disorders seen with fibromyalgia may actually be a cause, as opposed to symptom – of the syndrome. Stage 4 sleep is the deepest level of sleep and is the one that is most lacking in fibromyalgia sufferers. Evidence that sleep disturbance may be a possible of fibromyalgia was given by a study that was able to induce fibromyalgia-like symptoms in normal volunteers by depriving them of deep sleep.
It is during stage 4 sleep that a hormone called somatomedin C is released into the system. Without enough deep sleep, fibromyalgia sufferers show abnormally low levels of this hormone which is essential for the body to rebuild itself. Lack of this hormone may be causing the characteristic muscle pain and fatigue commonly seen in fibromyalgia. Also, release of growth hormone occurs primarily during stage 3 and stage 4 of non-REM sleep. Thus disturbed sleep will affect the release of this hormone causing abnormalities in your body. One third of patients with fibromyalgia have low insulin growth factor (IGF) levels, an indication of low growth hormone secretion. Interestingly, amongst fibromyalgia sufferers, the severity of the sleep disorder seems to correlate with the number of tender points they have (see below for an explanation on tender points).
Sleep deprivation is also known to cause some of the symptoms involved with “fibrofog.” People who lack enough sleep or poor deep sleep have been known to experience feelings of being in a fog, loss of control of though processes and poor memory.
Studies have shown that exercise increases the amount of time spent in deep sleep. Thus, it is not surprising that exercise has been confirmed to be of value in the treatment of fibromyalgia. See the section on Treatments for more information on appropriate exercise regimens.
Injury or Microtrauma to Muscles
It has been suggested that the pain of fibromyalgia may be related to microtrauma in deconditioned muscles and that exercise helps fibromyalgia sufferers by conditioning these muscles. For example, pain in the muscle causes spasm in the muscle, causing more pain, which in turn causes more spasm. The muscle becomes chronically congested, and the delivery of oxygen and other nutrients, as well as the removal of metabolic wastes and acids, becomes impaired.
A recent study looked at the relationship between neck injuries and the onset of fibromyalgia. It found that fibromyalgia was 13 times more likely to occur following a neck injury than an injury to the lower bodies.
However, muscle biopsies have not been able to identify any difference in sore muscles when compared to other non-tender parts of the body. Also, some tender points are not over muscles or tendons but over bones or fat pads. Scans of fibromyalgic muscle tissue by electron microscope have revealed some abnormalities in the levels of a muscle sugar called glycogen. Abnormal organelles called mitochondria that are involved in energy production have also been found in fibromyalgia patients. So while there is some evidence that abnormalities in the metabolic properties of the muscles may be involved in fibromyalgia, it is more probable that these injuries to muscles don’t cause fibromyalgia, but rather, they may awaken a hidden genetic predisposition.
Another way whereby injuries may be involved with fibromyalgia is that an injury to the upper spinal region may affect the central nervous system and may trigger the development of fibromyalgia in some people. The brain is easily overwhelmed by head injury, viruses, and severe stress. When an injury to the brain occurs, it triggers a cascade of biological events involving neurotransmitters, hormones and changes in blood flow, to protect the traumatized area. Unfortunately for the patient, such defensive action by the brain can cause serious problems in the body. Some of the things that they can cause are many of the same symptoms that fibromyalgia patients may be suffering from. Several studies are currently analyzing brain wave activity to see if there are differences between normal people and fibromyalgia sufferers.
Other Possible Causes
Other less frequently theorized causes include:
Central nervous system dysfunction. Some believe that fibromyalgia sufferers have an abnormal nervous system that leads to abnormal processing of sensory stimuli. This means that the patient’s nervous system processes normally non-painful sensory stimuli as being painful. This phenomenon in which pain results from a stimulus that should not normally be painful is known as allodynia.
Changes in muscle metabolism, such as decreased blood flow, causing fatigue and decreased strength.
Infectious agents such as a virus but no such agent has been identified. Also, if fibromyalgia were infectious we would expect so see an increased incidence in spouses of an affected patient and this is not the case.
Immune system abnormalities. Several changes in immune system function have been found in fibromyalgia, generally in the direction of increased activity. Hyperactive immune system symptoms can be induced in normal volunteers through sleep deprivation. This may link sleep dysfunction and immune function as causative agents in fibromyalgia.
Muscle tension. Muscles that are in a chronic state of contraction will not relax fully, even with rest. Muscles constantly taxed this way can produce an unlimited variety of unpleasant symptoms. It should also be noted that contracted muscles not only cause the brain to release certain chemicals that can cause pain, but that they greatly restrict the oxygen that they take in, which can produce drastic side effects since oxygen is responsible for regulating the fluid levels in soft tissues as well as repairing injuries.
Tense muscles can also press adjacent nerves, causing pain, tingling and numbness. Stressed nerves can create weakness in affected muscles and restrict motion in nearby joints. A muscle’s constant state of contraction will cause it to shorten, limiting motion and causing muscle aches and stiffness.
Genetic predisposition. Although no specific inheritance pattern has been identified, an increased incidence in relatives of affected patients had been noted. Therefore, development of fibromyalgia may involve certain predisposing factors that are inherited, as well as precipitating factors such as trauma, infection, stress or sleep disruption. Current studies on twins with fibromyalgia are examining the possibility of genetic predisposition to the syndrome.
Current research is looking that the significance of spinal stenosis (narrowing of the spinal canal) or Chiari malformations and fibromyalgia.
