Monday, July 27, 2009

Fibromyalgia and its Sufferings

Understanding Chronic Pain and Fibromyalgia: A Review of Recent Discoveries

Fibromyalgia tends to be treated rather dismissively, sometimes with cynical overtones. When I trained in BPT some 10 years ago, this diagnosis was never mentioned. In the United States fibromyalgia has become a semi-respectable diagnosis within the last 10 years, but even so it has some critics. The problem for doctors is that fibromyalgia is not a problem that can be understood according to the classic medical model. This is the model that is used in all medical training. It is based on the correlation of specific tissue pathology with distinctive symptoms (e.g. tuberculosis of the lung causing a chronic cough). Elimination of the causative agent (e.g. the tubercule bacillus) cures the disease. This model has led to the most major advances in medicine that we benefit from today.

I have seen over 150 fibromyalgia patients over the past 5 years; most want to be reassured that their symptoms are the product of a "real disease" rather than figments of a fertile imagination--commonly ascribed to the psychological diagnosis such as somatization, hypochondriasis, or depression. The good news is that contemporary research is hot on the track of unraveling the changes that occur within the nervous system of fibromyalgia patients. The basic message is that fibromyalgia cannot be considered a primarily psychological disorder, but as in many chronic conditions, psychological factors may play a role in who becomes disabled and may even up-regulate the central nervous system changes that are the root cause of the problem.

What is the problem?
The problem is: disordered sensory processing.
I will try to convey to you what we mean by "disordered sensory processing." Even a superficial understanding of this topic will change the way you think about the fibromyalgia problem. Furthermore, recent advances that have been made at the molecular level hold out the promise of more effective treatment for fibromyalgia pain.

What is Fibromyalgia?
Fibromyalgia is a chronic pain state in which the nerve stimuli causing pain originates mainly in the muscle. Hence the increased pain on movement and the aggravation of fibromyalgia by strenuous exertion.

Pain is a universal experience that serves the vital function of triggering avoidance. A few unfortunate individuals have a congenital absence of pain sensation; they do not fare well due to repeated bodily insults that go unnoticed. As a physician I see patients with an acquired deficiency in the pain sensation (e.g. diabetic neuropathy or neurosyphilis) who develop a severe destructive arthritis--a result of repeated minor joint injuries that are overlooked. Thus pain sensation is a necessary part of being human. Pain sensation is a fact of life. Even the primitive amoeba takes avoiding action in the face of adverse events. In such primitive life forms, pain avoidance is purely reflex action, as they do not have the complexity of a highly developed brain to feel pain in the sense that humans do: (1)The unconscious reflex avoidance reaction that is so rapid that it occurs before the actual awareness of the pain sensation (as in all life forms), (2) the actual experience of the pain sensation (that can only occur in highly complex organisms). This is an important point, as it implies that different parts of the brain are involved in these two consequences of the pain reaction.

Over the last few years a number of important research discoveries have started to clarify the enigma of chronic pain. Many of these new findings have a special relevance to the chronic pain of fibromyalgia. The cardinal symptom of FM is widespread body pain. The cardinal finding is the presence of focal areas of hyperalgesia, the tender points. Tender points imply that the patient has a local area of reduced pain threshold, suggesting a peripheral pathology. In general, tender points occur at muscle tendon junctions, a site where mechanical forces are most likely to cause micro-injuries. Many--but not all--FM patients have tender skin and an overall reduction in pain threshold. These latter observations suggest that some FM patients have a generalized pain amplification state. There has been a recent plethora of experimental studies apposite to the pathophysiological basis of both the peripheral and central aspects of pain.

The Pathophysiological Basis for Chronic Pain
The International Association For the Study of Pain (ASP) defines pain as follows: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." This definition explicitly affirms that pain has both a sensory and an affective-evaluative component, and furthermore acknowledges that it may occur in the absence of obvious visceral or peripheral pathology. To fully understand chronic pain, one must integrate the sensory and affective/evaluative elements of the pain experience. It is equally misguided to focus on the psychological aspects of pain, as it is to address only the sensory component and ignore the affective dimensions. However, for the sake of clarity, each of these two constitutive elements will be considered separately.

The Sensory Component
Pain is generally envisaged as a cascade of impulses that originates from nocioceptors in somatic or visceral tissues. The impulses travel in peripheral nerves with a first synapse in the dorsal horn and a second synapse in the thalamus, and end up in the cerebral cortex and other supraspinal structures.

This results in an experience of pain and the activation of reflex and later reflective behaviors. These reflex and reflective behaviors are aimed at eliminating further pain. The expectation is that this nocioceptor driven pain will be successfully abolished, allowing healing and a return to a pain-free state. The problem with chronic pain is that the linear relationship between nocioception and pain experience is inappropriate or even absent, and the expected recovery does not occur.

It is a common misconception to view the nervous system as being "hard-wired"; that is, stimulation of a nerve ending (say a needle prick) always produces the same behavioral and affective response. This concept implies that the same intensity of pain stimulus will always elicit the same degree of nerve stimulation and hence the same subjective experience of pain. It is now understood that the concept is wrong. Some 30 years ago, Melzeck and Wall proposed that pain is a complex integration of noxious stimuli, affective traits, and cognitive factors. In other words, the emotional aspects of having a chronic pain state and one's rationalization of the problem may both influence the final experience of pain. Mendell and Wall provided the first experimental evidence that the nervous system was not hard-wired in 1965. They noted that a repetitive stimulation of a peripheral nerve, at sufficient intensity to activate C-fibers, resulted a progressive build-up of the amplitude of the electrical response recorded in the second order dorsal horn neurons. If the system had been hard-wired, each stimulus would have elicited the same response in the second order neuron. They termed this phenomenon "wind-up." It is now appreciated that the phenomenon of wind-up is crucial to understanding the problem of chronic pain via the mechanism of "central sensitization."

Central sensitization refers to an increased activation of second order neurons in the spinal cord, resulting from injury or inflammation-induced activation of peripheral nocioceptors. Sensory input from muscle, as opposed to skin, is a much more potent effector of central sensitization. This may be the clue to the role of muscle pain in the total spectrum of fibromyalgia. A common example of central sensitization is post-herpetic neuralgia. Previous injury to a peripheral nerve leads to an amplification of both nocioceptive and non-nocioceptive impulses. The mechanism responsible for the abnormal perception of non-nocioceptive impulses in post-herpetic neuralgia is an increased excitation of second order nocioceptive neurons in the dorsal horn of the spinal cord. A special example of central pain occurs when there is pathology within the central nervous system. This occurs in a thalamic stroke--severe unilateral pain, often accompanied by strong emotions, that occurs in the absence of any nocioceptive input.

There are two forms of second order spinal neurons involved in central sensitization. (1) Nocioceptive--specific neurons--respond only to nocioceptive stimuli, and (2) Wide dynamic range neurons--respond to both nocioceptive and non-nocioceptive afferent stimuli. Both may be sensitized by nocioceptive stimuli leading to central senitization but wide-dynamic range neurons are generally more intensely sensitized than nocioceptive-specific neurons. Nocioceptive and non-nocioceptive peripheral nerves often converge onto the same wide dynamic range neuron (see figure). Once sensitized by ongoing nocioceptive impulses from peripheral nerves, wide-dynamic range neurons will respond to non-nocioceptive stimuli just as intensely as they did prior to sensitization. This results in sensitizations like a light touch to be experienced as pain (i.e. allodynia). Sensitization of wide-dynamic range neurons by prior pain stimuli provides the pathophysiological foundation for nonnocioceptive pain.

There is emerging evidence that afferent activity from Golgi tendon organs and muscle spindles can be converted into pain signals under the influence of central sensitization. For instance, some patients with strokes and spinal cord injuries develop severe pain on movement. Benc has proposed the term "proprioceptive allodynia" to describe this phenomenon. He describes such individuals as "while not experiencing pain at rest, they develop excruciating burning and tingling, often difficult to describe, that appear only when trying to hold an object, move a limb, stand or walk." Thus everyday muscle activity may cause pain and impair function in some individuals with central sensitization. At a physiological level, pain on movement implies that proprioceptive afferents are projecting onto second order wide-dynamic-range spinal neurons that have been sensitized by previous nocioceptive activity. Thus the central nervous system of subjects who have ongoing pain (e.g. arthritis) or have had previous pain experiences (e.g. post injury pain) may be permanently altered due to changes that can now be understood at the physiological molecular and structural levels. At a clinical level this is seen as persistent pain in survivors of serious illness who experienced high levels of pain during hospitalization, persistent pain after breast surgery, or the occurrence of fibromyalgia after automobile accidents. The reason why the phenomenon of central sensitization only occurs in a minority of individuals is not currently known. At a molecular level, there are many studies demonstrating the important role of excitatory amino acids such as glutamate and neuropeptides such as substance P in the generation of central sensitization. Substance P and CRGP are important neurotransmitters in lowering the threshold of synaptic excitability, which permits the unmasking of normally silent interspinal synapses and the sensitization of second order spinal neurons. Substance P, unlike the excitatory amino acids, can diffuse long distances in the spinal cord and sensitize dorsal horn neurons in spinal segments both above and below the input segment--with resulting pain signal generation from non-nocioceptive afferent activity. Clinically this will lead to an expansion of receptive fields; e.g. the spread of pain from to uninjured areas after an automobile accident.

The Psychological Component
It was seen in the preceding section that chronic pain could occur in the absence of ongoing tissue damage--this is an example of the sensory component of pain. It was also noted that one component of pain is a reflex avoidance behavior that can occur before the conscious appreciation of pain. In terms of brain physiology this implies that more primitive parts of the brain contain several discrete nuclei (e.g. the thalamus, cingulate gyrus, hippocampus, amygdyala, and locus ceruleus) that interact to form a functional unit called the limbic system. This is the part of the brain that subserves many reflex phenomena, including the association of sensory input with specific mood states (e.g. pleasure, fear, aversion etc.). These facts form the physiological basis for considering the emotional aspect of pain. Interestingly, the electrical stimulation of the brain during neurosurgical procedure does not induce pain sensations in pain-free subjects. However, in past pain patients it often reawakens previous pain experiences. It is surmised that such stimulation re-activates cortical and subcortical pain circuits that were previously dormant. It is not known whether there is a single cortical structure that subserves pain memory. Currently it appears that different cortical and subcortical structures are involved in the pain experience. For instance, removal of the somatosensory cortex does not abolish chronic pain, but excision of lesions of the anterior cingulated cortex reduces the unpleasantness of pain. The anterior cingulated cortex is involved in the integration of affect cognition and motor response aspects of pain and exhibit increased activity on PET studies of pain patients. Other structures involved in cortical pain processing include the prefrontal cortex (activation of avoidance strategies, diversion of attention and motor inhibition); the amygdala (emotional significance and activation of hypervigilance); and the locus ceruleus (activation of the "fight or flight" response).

All these structures are linked to the medial thalamus, whereas the lateral thalamus is linked to the somatosensory cortex (pain localization). One example of limbic system activation is the hypervigilance that accompanies many chronic pain states, including fibromyalgia.

The emotional component of pain is multifactorial and includes past experiences, genetic factors, generals state of health, the presence of depression and other psychological diagnosis, coping mechanisms, and beliefs and fears surrounding the pain diagnosis. Importantly, thoughts as well as other sensations can influence the sensory pain input to consciousness as well as the emotional coloring of the pain sensation. The term given for this modulation of pain impulses is the "gate control theory of pain." Thus thoughts (beliefs, fears, depression, anxiety, anger, helplessness, etc.), as well as peripherally generated sensations, can both dampen or amplify pain. Indeed, in many chronic pain conditions (that lack any effective therapy for the sensory/pain component), a reduction of pain and the resulting suffering can only be affected by modulating the psychological aspects of pain. As the psychological contribution to pain varies enormously from patient to patient, this approach has to be individualized. However, there are some general principles that are worth noting. There are important consequences of having pain that will not go away (as is the expected experience for most pain in most people). The unsettling realization that the problem may well be life-long generates a varied mix of emotions and behaviors that are often counterproductive to coping with a chronic problem. Many of these changes (which are partly reflex in origin) would be appropriate for dealing with acute self-healing pain events, but become a liability when dealing with chronic pain. The end result of chronic pain is often depressive illness, marital discord, vocational difficulties, chemical dependency, social withdrawal, sleep disorders, increasing fatigue, inappropriate beliefs, and a radical alteration in their previous personality. Varying degrees of functional disability are a common accompaniment of chronic pain states. The reasons for dysfunction are multiple and vary from individual to individual. Pain often monopolizes attention (causing lack of focus on the task at hand). It is usually associated with poor sleep (causing emotional fatigue). Movements may aggravate pain (causing a reluctance to engage in activity). Fear of activity often leads to deconditioning (which predisposes to muscle and tendon injuries and reduced stamina). Pain causes stress, which may result in anxiety, depression, and inappropriate behavior (causing disability due to secondary psychological distress). The modern era of psychological imaging is providing an important new framework for understanding these "emotional" responses

Newly Diagnosed Patient

Fibromyalgia (fi-bro-my-AL-ja) is a very common condition of widespread muscular pain and fatigue. Seven to ten million Americans suffer from fibromyalgia (FM). It affects women much more than men in an approximate ratio of 20:1. It is seen in all age groups from young children through old age, although in most patients the problem begins in their 20s or 30s. Recent studies have shown that fibromyalgia occurs worldwide and has no specific ethnic predisposition.

The Symptoms of Fibromyalgia

Fibromyalgia patients have widespread body pain which often seems to arise in the muscles. Some FM patients feel their pain originates in their joints. Pain that emanates from the joints is called arthritis; extensive studies have shown FM patients do not have arthritis. Although many fibromyalgia patients are aware of pain when they are resting, it is most noticeable when they use their muscles, particularly during repetitive activities. Their discomfort can be so severe it may significantly limit their ability to lead a full life. Patients can find themselves unable to work in their chosen professions and may have difficulty performing everyday tasks. As a consequence of muscle pain, many FM patients severely limit their activities including exercise routines. This results in their becoming physically unfit, which eventually makes their fibromyalgia symptoms worse.

In addition to widespread pain, other common symptoms include a decreased sense of energy, disturbances of sleep, and varying degrees of anxiety and depression related to patients' changed physical status. Furthermore, certain other medical conditions are commonly associated with fibromyalgia, such as: tension headaches, migraine, irritable bowel syndrome, irritable bladder syndrome, premenstrual tension syndrome, cold intolerance, and restless leg syndrome. Patients with estalished rheumatoid arthritis, lupus (SLE), and Sjogren's syndrome often develop FM during the course of their disease. The combination of pain and multiple other symptoms often leads doctors to pursue an extensive course of investigations, which are nearly always normal.

Diagnosing Fibromyalgia

There are no blood tests or X-rays that show abnormalities diagnostic of FM. This initially led many doctors to believe that the problems suffered by FM patients were "all in their heads," or that fibromyalgia patients had a form of masked depression or hypochondriasis. Extensive psychological tests have shown these impressions were unfounded. A physician's diagnosis of FM is based on taking a careful history and the finding of tender areas in specific areas of muscle. These locations are called "tender points." They are tender to palpation and often feel somewhat hardened if the muscle is stroked.

The Long-Term Outcome for Fibromyalgia

The musculoskeletal pain and fatigue experienced by fibromyalgia patients are chronic problems that tend to have a waxing and waning intensity. There is currently no generally accepted cure for this condition. According to recent research, most patients can expect to have this problem lifelong. However, worthwhile improvement may be obtained with appropriate treatment. There is often concern on the part of patients, and sometimes physicians, that FM is the early phase of some more severe disease, such as multiple sclerosis, lupus , etc. Long-term follow-up of fibromyalgia patients has shown that it is very unusual for them to develop another rheumatic disease or neurological condition.

However, it is quite common for patients with "well-established" rheumatic diseases, such as rheumatoid arthritis, systemic lupus, and Sjogren's syndrome, to have fibromyalgia also. It is important for these patients' doctors to realize they have such a combination of problems, as specific therapy for rheumatoid arthritis and lupus, etc. does not have any effect on FM symptoms. Patients with fibromyalgia do not become crippled with the condition, nor is there any evidence it affects their lifespan. Nevertheless, due to varying levels of pain and fatigue, there is an inevitable contraction of social, vocational, and avocational activities that leads to a reduced quality of life. As with many chronic diseases, the extent to which patients succumb to the various effects of pain and fatigue are dependent upon numerous factors, in particular their psycho-social support, financial status, childhood experiences, sense of humor, and determination to push on.

The Treatment of Fibromyalgia

The treatment of FM is frustrating for both patients and their physicians. In general, drugs used to treat musculoskeletal pain, such as aspirin, non-steroidals (e.g. ibuprofen), and cortisone, are not particularly helpful in this situation. As in any chronic pain condition, education is an essential component that helps patients understand what can or can't be done as well as teaching them to help themselves.

It is important for a patient's physician to discover whether there is a cause for sleep disturbances. Such sleep problems include sleep apnea, restless legs syndrome, and teeth grinding. If the cause for a patient's sleep disturbance cannot be determined, low doses of an anti-depressive group of drugs, called tricyclic anti-depressants or short acting sleeping medications such as zolpidem (Ambien) may be beneficial. Patients need to understand these medications are not addictive when used in low dosages (eg., amitriptyline 10 mg at night) and have very few side effects. In general, routine use of sleeping pills such as Halcion, Restoril, Valium, etc., should be avoided as they impair the quality of deep sleep. It is claimed that Ambien (zolpidem) avoids this problem.

There is increasing evidence that a regular exercise routine is essential for all fibromyalgia patients. The increased pain and fatigue caused by repetitive exertion makes regular exercise quite difficult. However, those patients who do develop an exercise regimen experience worthwhile improvement and are reluctant to give up. In general, FM patients must avoid impact loading exertion such as jogging, basketball, aerobics, etc. Regular walking, the use of a stationary bicycle, and pool therapy utilizing an Aqua Jogger (a floatation device that allows the user to walk or run in the swimming pool while remaining upright) seem to be the most suitable activities for FM patients. Supervision by a physical therapist or exercise physiologist is of benefit wherever possible. In general, 20 minutes of physical activity three times a week at 70% of maximum heart rate (220 minus your age) is sufficient to maintain a reasonable level of aerobic fitness.

Drugs such as aspirin and Advil are not particularly effective and seldom do more than take the edge off FM pain. Opioid analgesics (propoxyphene, codeine, morphine, oxycodone, methadone) may provide a worthwhile pain relief in a subgroup of severely afflicted patients, but fibromyalgia patients seem especially sensitive to opioid side effects (nausea, constipation, itching, and mental blurring) and often decide against the long-term use of these drugs. The use of opioid analgesics (narcotics) in the management of non-malignant pain has been a controversial issue for many doctors, with the usual reasons for concern: addiction, oversight by state medical boards, and criminal diversion of drugs. However, recent research has shown that addiction seldom occurs when these medications are use in chronic pain states. It is important to understand the difference between addiction and dependence (which occurs with all these drugs in the majority of patients (see Addiction/Dependence). Two particularly useful weak opioids in the management of FM pain are tramadol (Ultram) and the combination of tramadol with acetaminophen (Ultracet). Neither of these two medications is a FDA scheduled drug (i.e. they have minimal addiction potential).

Particularly painful areas often may be helped for a short time (2-3 months) by trigger point injections. This involves injecting a trigger point with a local anesthetic (usually 1% Procaine) and then stretching the involved muscle with a technique called spray and stretch. It should be noted the injection of a tender point is quite painful (indeed, if it is not painful the injection is seldom successful). After the injection, there is typically a lag of two to four days before any beneficial effects are noted. Other techniques that directly help the tender areas on a transient basis are heat, massage, gentle stretching, and acupuncture.

About 20 percent of FM patients have a co-existing depression or anxiety state that needs to be appropriately treated with therapeutic doses of anti-depressants or anti-anxiety drugs often in conjunction with the help of a clinical psychologist or psychiatrist. Basically, patients who have a concomitant psychiatric problem have a double burden to bear. They will find it easier to cope with their FM if the psychiatric condition is appropriately treated. It is important to understand that fibromyalgia itself is not a psychogenic pain problem, and that treatment of any underlying psychological problems does not cure FM.

Most FM patients quickly learn there are certain things they do on a daily basis that seem to make their pain problem worse. These actions usually involve the repetitive use of muscles or prolonged tensing of a muscle, such as the muscles of the upper back while looking at a computer screen. Careful detective work is required by the patient to note these associations and, where possible, to modify or eliminate them. Pacing of activities is important; we have recommended that patients use a stopwatch that beeps every 20 minutes. Whatever they are doing at that time should be stopped and a minute should be taken to do something else. For instance, if they are sitting down, they should get up and walk around--or vice versa.

Patients who are involved in fairly vigorous manual occupations often need to have their work environment modified and may need to be retrained in a completely different job. Certain people are so severely affected that consideration must be given to some form of monetary disability assistance. This decision requires careful consideration, as disability usually causes adverse financial consequences as well as a loss of self esteem. In general, doctors are reluctant to declare fibromyalgia patients disabled and most FM applicants are initially turned down by the Social Security Administration at the first review. However, each patient needs to be evaluated on an individual basis before any recommendations for or against disability are made.

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