Meta Analysis of Fibromyalgia Treatment From Traditional to Complimentary

Fibromyalgia syndrome (FMS) is a complex medical condition that affects about 5 million American people. The condition is characterized by "chronic widespread pain, fatigue, sleep disturbance, stiffness, impaired memory and concentration, anxiety and depression." (Facts of Life, 2001). Sleep disturbance and an increased sensitivity to pain follow a cyclic pattern in individuals having FMS, the result of which is a positive feedback loop. (Etiology of Fibromyalgia, 2003).

Typically, fibromyalgia affects women, especially those between the ages of 20 and 55. (Who gets fibromyalgia? 2003). Women in this age group, as also people with rheumatologic or endocrine problems (such as thyroid disease), are at greatest risk for developing fibromyalgia syndrome. Fibromyalgia can also manifest at the time of menopause, and the malaise has also been seen to exist among members of the same family in successive generations. This syndrome also sometimes affects men and children.

The cause of fibromyalgia is yet unknown, and many researchers believe that abnormalities in the central nervous system or in the functioning of the neuro-endocrine systems may be causative factors. Research is underway as to the possible triggers and the concurrent occurrence between fibromyalgia and other medical conditions such as chronic fatigue syndrome and irritable bowel syndrome. Factors that may contribute to the development of this syndrome in an individual include emotional stress, injury or trauma, muscle function, changes in serotonin levels, and a family history of fibromyalgia. (Facts of Life, 2002). Weather changes, increased physical activity, physical or mental stress, and lack of sleep, can act as triggers, inducing fibromyalgia symptoms. The individual's sensitivity to these triggers also increases progressively with continued exposure to them. It is suspect also, that infections may play a role, although there is no definite evidence. In the absence of clear evidence as to the cause of FMS, its treatment can only be limited to managing the symptoms through exercise, education, cognitive-behavioral therapy, medication and physical rehabilitation. (Facts of Life, 2002).

Historical Evolution of Fibromyalgia (FM):

Symptoms of fibromyalgia were first described in the early 1800s. Physicians recognized the signs and symptoms of what we now call fibromyalgia and used the term muscular rheumatism, to describe the same condition. It has also been called chronic rheumatism, myalgia, and fibrositis. (De Blecourt & Knipping, 2002). Yet other names have been used by the medical profession, to describe the different forms of non-articular rheumatism: fibrositis syndrome, interstitial myofibrositis, Muskelschwiele (muscle callus or welt), myogelosen (muscle gelling), Muskelh rten (muscle hardening), muscular rheumatism, non-articular rheumatism, or Weichteil rheumatismus (soft-tissue rheumatism), myofascial (pain) syndrome, myofascitis, or trigger points, and myalgia or myalgic spots. (De Blecourt & Knipping, 2002).

In the early years, physicians attributed the painful condition to the stresses and strains of modern life. They also often ascribed to it a psychosomatic origin, and some believe that it is psychological in nature. Others attributed it to an inflammation in the body's fibrous tissue. A review of the research has indicated that as many as 80% of people diagnosed with fibromyalgia also have chronic fatigue syndrome; likewise, about 80% suffer from chronic headaches; 75% have temporo-mandibular disorders, up to 60% have irritable bowel syndrome, and 33% have multiple chemical sensitivity. (De Blecourt & Knipping, 2002).

Fibromyalgia (FM) was often misdiagnosed before the 1980's, because there is no clear diagnostic procedure, either based on X-rays or through laboratory tests. There is no diagnostic marker in the blood. (Overview: What is Fibromyalgia?, 2001). Also, people with FM often look healthy. The etiology of fibromyalgia syndrome still remains elusive, and the absence of a uniform pathophysiogical basis to the condition means that it cannot be regarded as a distinctive disease.

In 1824, a doctor in Edinburgh described 'tender points' in the body. In 1880, a psychiatrist in the United States described the same conditions - a collection of symptoms consisting of fatigue, widespread pain, and psychological disturbances - and called it neurasthenia, and attributed it to physical and mental stress. (Nagy, D.K., 2002).

In 1904, Sir William Gowers used the term "fibrositis" in a paper on lumbago, to refer to the sore points found in patients suffering from muscular rheumatism. He described muscular rheumatism as an inflammation of fibrous tissue of the muscle, and explained that the inflammation in lumbago originated behind the sacrum and spread to the fibrous sheath of the sciatic nerve, resulting in widespread pain. According to Gowers, factors, which precipitate the symptoms, included exposure to cold, and acute and chronic muscular over strain. (Stonecypher, S.M., 1999).

Luff wrote about the factors precipitating fibrositis, in the British Medical Journal in 1913. He observed that the symptoms worsened when rain was in the offing, usually preceded by a lowering of atmospheric pressure. Luff explained how factors such as temperature variations, fevers, infections and accidents could act as triggers, precipitating or aggravating the symptoms of fibrositis in chronic sufferers. (Stonecypher, S.M., 1999).

Between 1970 and 1990 researchers like Yunus, Campbell and Smythe have proposed several sets of criteria for the diagnosis of fibromyalgia. Smythe (1980) defined certain diagnostic criteria such as widespread aching of more than 3 months' duration; local tenderness at 12 of 14 specified sites; skin roll tenderness over the scapular region; and disturbed sleep, with morning fatigue and stiffness. (De Blecourt & Knipping, 2002).

In 1981, Yunus defined certain obligatory criteria and some major and minor criteria for the diagnosis of what he called primary fibromyalgia syndrome. Obligatory criteria included the presence of generalized aches and pains or prominent stiffness, involving 3 or more anatomic sites, for at least 3 months. Major criteria included the presence of at least five typical and consistent tender points. Minor criteria such as sleep disturbance, anxiety, chronic headaches and the aggravation of symptoms by physical activity or by stress, were also listed. Yunus' criteria for diagnosis required that patients must satisfy the 2 obligatory criteria, as well as either the major criterion in addition to at least 3 minor criteria, to be diagnosed with primary fibromyalgia. (De Blecourt & Knipping, 2002).

Campbell (1983) devised a questionnaire to define whether fibromyalgia syndrome was present in the individual, as a kind of diagnostic measure. Patients were asked to answer in all, 15 questions, such as " I have pain in my muscles and joints" or "My pain is affected by weather," and so on. Diagnosis would be based on the responses to these questions. (De Blecourt & Knipping, 2002).

The American Medical Association (AMA) first recognized Fibromyalgia as a "true" illness and the cause of disability, in 1987. Goldenberg reported on the symptoms and treatment in 118 patients having fibromyalgia, in an article published in the Journal of the American Medical Association (JAMA), in 1987. Doctors are however still cautious before pronouncing a diagnosis of fibromyalgia, because of the lack of any clear-cut clinical evidence pointing to this condition. (Nagy, 2002)

Simons and Travell have conducted extensive research on a related condition called the myofascial pain syndrome. An international symposium on myofascial pain and fibromyalgia was held in Minneapolis, USA, in 1989. Myofascial pain syndrome is characterized by trigger points in the muscle tissues or fibers. A trigger point is defined by Travell as "circumscript tenderness, a localized twitch or fasciculation on stimulation by pressing or pinching that portion of the muscle, which contains the trigger area, and referred pain produced by pressure on the trigger point." Myofascial pain syndrome is developed when a trigger point develops in a muscle. This happens when a muscle is overworked and fatigued, chilled or severely traumatized. These factors are considered as direct causes, while other factors (other trigger points, arthritic joints, and emotional stress) are considered as indirect causes, in the sense that they create conditions that lead to the development of the triggerpoint.

The Copenhagen Declaration" on fibromyalgia was formalized at the second World Congress in 1992 in Copenhagen. Several international experts on fibromyalgia helped summarize the different aspects of the fibromyalgia syndrome, in this document. According to a review titled "Fibromyalgia: a clinical challenge" by Lorentzen, the symptoms often reported by patients suffering from fibromyalgia actually reflect the difficulties they experience in coping with various types of environmental stress. The experienced stress may lead in turn to sleep disturbances, fatigue and a low level of physical activity and fitness. This again may lead to muscle pain and tenderness. The syndrome becomes chronic because of the vicious circle that is thus set in motion. Lorentzen explains that these factors causing stress need to be identified early so that early intervention is made possible. (De Blecourt & Knipping, 2002).

Fibromyalgia syndrome is unique in many ways, but has been found to overlap with other unexplained comorbid medical conditions, including irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), temporomandibular disorder (TMD), and migraine headache. Symptoms such as pain, fatigue, disturbed sleep, anxiety and depression are common to all of these conditions, and many people who have one of these conditions also meet the diagnostic criteria for at least one other. Studies on comorbid conditions have revealed that among people with fibromyalgia, as many as 80% also have CFS, 75% have TMD and as many as 60% have IBS. Some scientists believe that central nervous system dysfunction could be the cause of these unexplained conditions. Muhammad Yunus referred to these comorbid conditions as "central sensitivity syndromes." (Facts of Life, 2002).

Present Understanding of FM: (Again General Concept for the Concept Paper)

The diagnostic criteria for classifying fibromyalgia were finally established and published in 1990 by the American College of Rheumatology (ACR). These criteria were widely accepted because they reflected the results of research published by 20 clinical investigators throughout the United States and Canada.

The ACR criteria for the classification of FM are:

History of widespread pain (must be present for at least 3 months)

Pain is considered widespread when all of the following are present:

1. Pain in the left and right side of the body

2. Pain above and below the waist

3. Axial skeletal pain (cervical spine, anterior chest, thoracic spine, or low back)

Pain in 11 of the 18 tender point sites on digital palpation

1. Occiput bilateral, at the suboccipital muscle insertions

2. Low cervical bilateral, at the anterior aspects of the intertransverse spaces at C5-C7

3. Trapezius bilateral, at the midpoint of the upper border

4. Supraspinatus bilateral, at origins, above the scapular spine near the medial border

5. Second rib bilateral, at the second costochondral junctions, just lateral to the junctions on upper surfaces

6. Lateral epicondyle bilateral, 2 cm distal to the epicondyles

7. Gluteal bilateral, in upper outer quadrants of buttocks in anterior fold of muscle

8. Greater trochanter bilateral, posterior to the trochanteric prominence

9. Knees bilateral, at the medial fat pad proximal to the joint line

For a tender point to be considered positive, the subject must state that the palpation was painful." (De Blecourt & Knipping, 2002).

The ACR criteria assume that the symptoms associated with FM are: pain, sleep disturbance, fatigue, headaches, irritable bowel syndrome, numbness and tingling sensations, joint pain, chest wall pain, sensitivity to cold, memory and concentration difficulties, and anxiety and/or depression, and interstitial cystitis -an inflammatory disorder affecting the walls of the bladder. (De Blecourt & Knipping, 2002).

Role of Collagen in fibomyalgia

Collagen is a structural protein, constituting about one quarter of all of the protein in the body. Collagen provides structure to our bodies, and also protects and supports the softer tissues, connecting them with the skeleton. Collagen is a relatively simple protein, composed of three chains, wound together in the form of a tight triple helix, somewhat akin to the double helix of the DNA molecule. It occurs in the form of resilient sheets that support the skin and internal organs. Bones and teeth consist essentially of collagen impregnated with mineral crystals.

The role of collagen in fibromyalgia has been the subject of many research studies. Musculoskeletal pain caused by continuous and repetitive work has been found to occur frequently in people engaged for long hours in work involving repetitive motions e.g. polishing, cleaning, weaving, mail sorting, working for extended periods on the computer, etc. The same muscle fibres are constantly being used and activated during such repetitive work. Therefore these muscle fibres are most prone to overloading disorders. However it is not fully clear whether this localized overloading actually results in changed metabolism, inflammatory changes in the collagenous tissue, affecting afferent nociception.

Twenty people, who had been suffering from fibromyalgia for two to over fifteen years, participated in a 90-day evaluation to determine effects of collagen hydrolysat on symptoms of chronic fibromyalgia. Twelve of the participants had concurrant temporomandibular joint pain. Collagen hydrolysat is a food supplement with no known side effects. Participants were evaluated initially and then at 30-, 60-, and 90-day periods. Pain complaint levels decreased significantly in an overall group average, and dramatically with some individuals. It was concluded that patients with fibromyalgia and concurrent temporomandibular joint problems might experience significant improvement in their symptoms with the use of collagen hydrolysat." (Olson, Savage & Olson, 2002). In one case, high doses of a collagen product, helped relieve a patient suffering from musculoskeletal pain, within a few days. This led to the theory that pain is caused by damage to the myelin sheath of the nerve fiber. The theory ties in with the general belief that people with autoimmune diseases have difficulty digesting protein and cannot therefore repair cells efficiently. In this case, the body was able to repair the myelin sheath using the easily digestible collagen protein.

Sleep disturbance

Sleep disturbance is a key feature of FMS. (Chaitow, L., 2003). "A survey of over 1000 patients with fibromyalgia syndrome (FMS) and Chronic Fatigue Syndrome (CFS) showed that prior to their illness fewer than 1% had disturbed sleep, whereas during their illness this rose to over 90%. The findings reveal that muscular aches and pains in a patient having fibromyalgia are frequently the result of the same processes, which disturb their sleep. The same biochemical or hormonal imbalances that cause sleep disturbances also create muscular symptoms." (Chaitow, L., 2003). The lack of deep sleep again impacts the pain symptoms, setting off a chain reaction.

In order to gain an insight into how sleep disturbances affect individuals suffering from fibromyalgia syndrome, it is important to understand the sleep process. Normal sleep occurs in cycles of 90 minutes, covering four stages. During the first stage of light sleep, an individual has alpha brain-wave patterns. This is followed by stages 2 (beta), 3 (gamma), and 3 (delta), which are progressively deeper stages of sleep. These three stages are also known as non-REM sleep, given that the rapid eye movements (REM) which occur during dreaming is absent in these stages of sleep. Various studies have shown that nearly half of all people with fibromyalgia experience disturbed delta stages - caused by intrusive alpha wave periods - and wake up feeling as tired as they did when they went to bed. Stage 4 sleep is the deepest level of sleep and is the one that fibromyalgia sufferers cannot enjoy. That sleep disturbance may be a possible cause of fibromyalgia was indicated in a study in which fibromyalgia-like symptoms were induced in normal volunteers by depriving them of deep sleep. It was concluded, therefore, that sleep disorders accompanying fibromyalgia may actually be an underlying cause of the syndrome.

Hormones

It has been observed that people with FMS exhibit alpha-delta anomaly during sleep. A patient with fibromyalgia suffers from chronic sleep deprivation, and never enjoys delta level sleep. When he reaches the stage of delta sleep, alpha waves intrude and bring him back to shallow sleep or to a wide-awake state. During stage 4 sleep, a hormone called somatomedin C, which is essential for the body to rebuild itself, is released into the system. Fibromyalgia sufferers, who do not get enough deep sleep, show abnormally low levels of this hormone. Lack of somatomedin C. may be actually causing the muscle pain and fatigue commonly seen in fibromyalgia patients. Also, release of growth hormone occurs essentially during stage 3 and stage 4 of non-REM sleep. Thus disturbed sleep will affect the release of this hormone, causing abnormalities in the body. Further, a significant proportion of fibromyalgia sufferers have low insulin growth factor (IGF) levels, which indicates that there is depressed growth hormone secretion. "Growth hormone has a powerful effect on the connective tissue, and directly stimulates the production of fibroblasts and mast cells, ground substance and collagen fibers. It plays a significant role in wound healing, where rapid production of collagen fibers by many fibroblasts is necessary for repair. Delta-level sleep is impaired in fibromyalgia patients, and this negatively impacts the release of Growth hormone." (What Causes Fibromyalgia?, 2002).

Neurotransmitters

The central nervous system transmits pain signals along 3 separate pathways, viz., via the peripheral nerves, the spinal and, and the brain. The peripheral areas of the body are first exposed to painful stimuli, and certain chemicals called neurotransmitters are released into the spinal cord in response to these stimuli. These neurotransmitters ultimately activate various receptors in the brain, depending upon the intensity and duration of the stimuli. Severe or persistent pain from any source (e.g. injuries, arthritis, surgery, etc.) can result in a heightened sensitivity to pain itself. What was formerly being perceived as non-painful stimuli now becomes painful, and the sense of pain spreads beyond the original site of injury. Substance P (SP), a neurotransmitter released in the spinal cord, plays an important role in the spread of chronic pain. It is composed of 11 amino acids, and when levels of substance P. increase significantly in the cerebrospinal fluid, this neurotransmitter diffuses to neighboring neurons. The diffusion in turn causes neighboring neurons to become sensitized, resulting in the perception of pain, even in uninjured tissue. The concentration of SP is elevated threefold in the cerebrospinal fluid of FMS patients compared to normal control subjects. Patients with severe cases of FMS have a reduced pain threshold, an increased sensitivity to painful stimuli, and an increase in the duration of pain after stimulation. Thus, for the same painful stimulus, a person with higher levels of substance P. will feel more pain than a normal person. Another neurotransmitter that is of significance to fibromyalgia syndrome is beta-endorphin, found in the immune cells of patients with fibromyalgia. Beta-endorphin is involved in stress responses, pain suppression, and mood disorders. However, excessively high levels of beta-endorphin in the brain have been seen to suppress the immune system. One study found that the beta-endorphin levels of fibromyalgia patients is close to half that of the healthy population. Serotonin is a neurotransmitter that is found to occur at depressed levels in people suffering from fibromyalgia symptoms. Antidepressant medications raise levels of serotonin, which is usually indicated in cases of depression, migraines and gastrointestinal distress. (What Causes Fibromyalgia?, 2002).

Fibromyalgia Treatment

In the treatment of fibromyalgia syndrome, the major goals include reduction of pain, fatigue and depression symptoms. Also, the importance of achieving undisturbed sleep, as well as the need for the improvement of cardiovascular fitness cannot be overemphasized. Given that there is no clear pathophysiological basis for this condition, there is currently no known cure for fibromyalgia syndrome. However, fibromyalgia patients have been found to experience an overall improvement in the symptoms, after going through a comprehensive course of therapy. Medication per se can be only palliative, and needs to be supplemented by physical therapy and counseling. Ergonomics is especially important for people with fibromyalgia who do a lot of repetitive motion or sit in one spot all day, as do people working at computers. Reduction in work hours is also often indicated in such cases, coupled with a program of stretching and low-impact aerobic exercises, in addition to the appropriate medication.

Pharmcological interventions. Antidepressants such as amitriptyline or cyclbenzaprine hydrochloride, have been shown to be beneficial in decreasing depression, relaxing the craniofacial and skeletal muscles, as also in improving sleep and releasing endorphins. "These drugs act by blocking norepi-nephrine and serotonin re-uptake inhibition." (Boon, n.d.). However, these drugs also produce significant side effects, which cannot be ignored. Side effects include weight gain, palpitation and urinary retention. Benzodiazepines such as clonazepam also promote better sleep, relax craniofacial as well as skeletal muscles and help restless leg syndrome. These drugs can however become addictive. Analgesics like Ibuprofen have only limited use in FMS. (Boon, n.d.).

S-adenosyl-methionine or SAM-e is an antidepressant with anti-inflammatory actions. Alprazolam drugs like Xanax, and capsaicin creams, are sometimes used to decrease panic reactions, and drugs like zolpidem help alleviate problems of sleep disturbance. Injection of tender points with a 1% lidocaine solution or in combination with hydrocortisone acetate suspension is sometimes recommended in the case of patients having incapacitating areas of tenderness, but this again can be addictive, as the patient is likely to develop dependence.