Myalgic Encephalomyelitis, IVN, CFIDS, & Fibromyalgia-
By Doctor Erich Ryll
 

DISCUSSED BY: ERICH D. RYLL, M.D.
Assistant Clinical Professor of Medicine
Division of infectious & Immunologic Diseases
Department of International Medicine
University of California
Davis, California

        
        Fibromyalgia syndrome (FMS) is an underdiagnosed disorder of
        unknown etiology affecting over 5% of the patients in a general
        medical practice (Campbell 1983) and an estimated 2-4% of the
        general population (Wolfe 1993), women more often than men.
        Patients complain that they ache all over.  A large number of
        other symptoms are often present, particularly fatigue, morning
        stiffness, sleep disturbance, paresthesias, and headaches (see
        table 2).  On examination, areas of focal tenderness called
        tender points can be demonstrated in characteristic locations
        (table 3).  Most patients can be helped substantially with
        treatment.

    Etiology
        A comprehensive review of the many theories of the etiology of
        FMS is beyond the scope of this paper.  While there is still
        not a majority of FMS researchers who support any one theory,
        significant progress is being made in identifying an etiology,
        and much useful evidence has been collected.
        FMS was first described as an inflammatory condition (Gowers
        1904).  When no evidence of inflammation could be found and an
        association was noted with depression and stress, the concept
        of "psychogenic rheumatism" was advanced (Boland 1947), but a
        number of studies have established that FMS is neither a
        psychosomatic nor somatiform disorder and that when present,
        anxiety and depression are more likely to be the result than
        the cause of FMS (Goldenberg 1989, Yunus 1991, Dunne 1995).
        It has been suggested that the pain of FMS is related to
        microtrauma in deconditioned muscles and that exercise works by
        conditioning these muscles (Bennett 1989).  However, reports of
        muscle biopsy abnormalities other than disuse atrophy have been
        difficult to replicate (Schroder 1993), and some tender points
        are not over muscles or tendons, such as the one over the
        medial fat pad of the knee (Smythe 1989).  Muscle energy
        metabolism is normal in FMS (Simms 1994, Vestergaard-Poulsen
        1995).
        FMS may be due to non-restorative deep sleep (Moldofsky 1975,
        1993).  Patients with FMS often report insomnia or light sleep
        as well as an increase in FMS symptoms after disturbed sleep
        (Campbell 1983).  Abnormal amounts of alpha activity on the
        electroencephalogram of FMS patients during deep sleep have
        been reported (Hauri 1973, Moldofsky 1975).  FMS-like symptoms
        can be induced in normal volunteers by depriving them of deep
        sleep, except in subjects who exercise regularly (Moldofsky
        1975).  Controlled trials have confirmed the value of aerobic
        exercise in the treatment of FMS (McCain 1988).  Exercise
        increases time spent in deep sleep (Hobson 1968), perhaps the
        mechanism for its therapeutic effect.
        A number of changes in immune system function have been found
        in FMS, generally in the direction of increased activity, many
        of which can also be induced in normal volunteers through sleep
        deprivation (Moldofsky 1993).  Many of the symptoms of FMS
        may be caused by elevations, induced by abnormal sleep, in
        certain cytokines such as interleukin-2, which has been found
        to be elevated in FMS patients, and which causes FMS-like
        symptoms when given intravenously (Wallace 1990, Moldofsky
        1995).
        Serotonin appears to be important in FMS.  Serum levels of
        serotonin and its dietary precursor tryptophan are low in FMS
        (Russell 1996).  Amitriptyline, one of the medications often
        used to treat FMS (see below), blocks serotonin reuptake and
        increases deep sleep (Baldessarini 1985).  Serotonin is
        important in deep sleep and in central and peripheral pain
        mechanisms (Chase 1973).
        The concentration of substance P, a peripheral pain neuro-
        transmitter, is several times higher in the cerebrospinal fluid
        of FMS patients than in pain-free controls, implying a
        peripheral origin for FMS pain (Russell 1994).  A number of
        other neuroendocrine abnormalities have been identified in FMS
        patients (Crofford 1994, Moldofsky 1995, Russell 1996) which
        form the basis for other theories of the etiology of FMS.
        Although no specific inheritance pattern has been identified,
        an increased incidence in relatives of affected patients has
        been noted (Pellegrino 1989).  Development of the syndrome may
        require a predisposing factor, possibly inherited, as well as a
        precipitating factor such as trauma, infection, stress, or
        sleep disruption.  The immunologic abnormalities suggest an
        infectious etiology, but if FMS were infectious we would expect
        to see an increased incidence in spouses of an affected patient
        and not just in their children and this is not the case.
    Diagnosis
        Since FMS is a syndromic diagnosis, any patient who fits the
        diagnostic criteria of chronic, diffuse aching with tenderness
        in at least 11 of 18 characteristic locations (Table 3) has it
        by definition.  It is not possible to accurately diagnose FMS
        without knowing how to do a tender point examination.  It
        cannot be accurately diagnosed by exclusion.  One would expect
        medical students to have been taught in physical diagnosis how
        to examine for a disorder that accounts for more than 5% of a
        primary care practice but lamentably this is not yet the case
        in most medical schools.  If a patient has typical symptoms of
        FMS (Table 2) but does not meet the tender point criterion, a
        diagnosis of "possible FMS" may be assigned and a therapeutic
        trial of standard treatment offered.  Tender points should be
        looked for again on a return visit as they may be more evident
        on some days than others.
        Although there have been many abnormalities of laboratory and
        other tests reported in FMS, none is sufficiently sensitive nor
        specific to be useful diagnostically, so routine studies are
        not recommended.  Patients who haven't recently had a general
        medical evaluation should as part of the workup, and other
        tests should be ordered when the history or exam raises a
        question of something other than FMS.  In older patients a
        sedimentation rate may be useful to exclude polymyalgia
        rheumatica.  In patients with other symptoms of hypothyroidism,
        thyroid studies may be indicated.
        The current syndrome definition may not be the best one
        possible (Wolfe 1993).  It has been argued that tender points
        have been over-emphasized, probably because historically
        rheumatologists have been more involved in the diagnosis and
        treatment of FMS than other specialists.  In many patients who
        meet the criteria for diagnosis for chronic fatigue syndrome,
        the only difference between them and a typical FMS patient is
        the degree of pain.  Some of these patients followed over time
        will subsequently develop tender points and then fit the
        criteria for diagnosis of FMS.  70% of patients with FMS meet
        the CDC criteria for CFS (Buchwald 1987) and two thirds of
        patients with CFS meet the ACR criteria for FMS (Goldenberg
        1990b).  It seems unlikely that these patients have two
        separate disease processes.  Perhaps dividing these two groups
        of patients on the basis of whether or not they have prominent
        pain is as artificial as division on the basis of prominence of
        any of the other twenty or so associated symptoms.
        On the other hand, we are to some extent stuck with the current
        syndrome definition because it is these patients on whom all
        the important studies have been performed.  If the syndrome
        definition is altered, we can't be certain that all of these
        results still apply to the new syndrome.  This problem will
        disappear once we know the true etiology and can make an
        etiologic rather than syndromic diagnosis.

    Treatment
        Controlled studies have shown that amitriptyline (Goldenberg
        1986, Jaeschke 1991), cyclobenzaprine (Quimby 1989), alprazolam
        (Russell 1991), aerobic exercise (McCain 1988), and other
        interventions to be discussed later are of benefit in treating
        FMS, but the percentage of patients responding to each alone is
        small.  When gentle daily aerobic exercise, a consistent bed
        time with adequate amounts of sleep, and one of several
        medications to improve deep sleep are combined, as expected
        more patients improve.  This approach has not yet been studied
        rigorously, but in a retrospective chart review I found that 30
        of 36 patients (83%) had improved substantially with it, many
        of those to the point of having no aching most of the time.
        Trazodone, diphenhydramine, carisoprodol, and doxepin have
        similar effects on deep sleep and are also widely prescribed
        for sleep in FMS, but have not yet been studied in controlled
        blinded trials.  Cyclobenzaprine and diphenhydramine are
        pregnancy category B and thus preferable in women who are or
        are attempting to become pregnant.  Alprazolam is pregnancy
        category D and so should be avoided in these patients.
        Medications effective in the treatment of FMS appear to work
        mainly through an effect on deep sleep (Goldenberg 1986).  They
        should be started at the lowest possible dose and increased
        every few days to a week to maximum relief of daytime FMS
        symptoms without unacceptable side effects.  I allow patients
        to fine-tune the dose themselves.  The starting doses and
        ranges of several medications useful in the treatment of FMS
        are listed in Table 1 in roughly the order I tend to try them.
        Amitriptyline is an effective medication for FMS but it has
        frequent daytime side effects attributable to its long half
        life such as weight gain, dry mouth, and cognitive impairment.
        I usually start with shorter-acting medications which help
        sleep and are gone during the day.
        It is often necessary to try several different medications in
        succession and sometimes in combination before finding a
        regimen that works well.  Some tolerance often develops to the
        sedative effect of many of these, necessitating one or two dose
        increases after an initial good response to maintain efficacy.
        When switching from one medication to another, it is important
        to taper the first slowly as the second is increased to try to
        maintain sleep quality and avoid exacerbating FMS symptoms.
        Imipramine, steroids, and non-steroidal anti-inflammatory drugs
        (NSAIDs) have all been found to be no better than placebo
        (Goldenberg 1993).  While NSAIDs might be expected to be
        helpful if only for the analgesic effect, their tendency to
        cause some insomnia may cancel out the expected benefit.
        Narcotics and benzodiazepines other than alprazolam block stage
        4 sleep and so should be avoided.  While they may help
        symptomatically, they often make the patient feel worse the
        next day and may prevent her from ever being able to get to the
        point of being pain-free most of the time.  Tramadol and
        acetaminophen do not seem to interfere with sleep and are
        therefore a better choice for analgesia.
        Fluoxetine was found in one study to be ineffective except to
        symptomatically treat associated depression (Wolfe, 1994).  A
        second study found it effective in combination with
        amitriptyline (Goldenberg 1996), but this may have been because
        fluoxetine increases amitriptyline levels which weren't
        monitored.  A second serotonin re-uptake inhibitor, citalopram,
        was ineffective for FMS symptoms (Nxrregaard 1995).
        There are many other unstudied "alternative" drug and herbal
        treatments, some of which may in the future be proven effective
        in controlled studies.  I do not recommend these since they are
        as yet unproven scientifically and may have unrecognized
        toxicities, but I have given up trying to dissuade patients
        from trying them as long as it is not in place of conventional
        therapy.
        Daily, gentle, low-impact aerobic exercise helps (McCain 1988),
        but too much or the wrong kind of exercise may exacerbate FMS
        symptoms.  Patients who are deconditioned should start out with
        just 3-5 minutes of exercise every day and increase as
        tolerated, usually up to 20-30 minutes a day.  The benefit of
        the exercise seems to be from its systemic effects rather than
        any direct effect on the exercised muscles.  It works better if
        the patient avoids exercising the most painful muscles.
        Patients should try different ways of exercising to find the
        best kind for them.  Walking or bicycling outside or various
        kinds of home exercise equipment are the most popular.  Aerobic
        water exercise may be best tolerated because it eliminates
        weight-bearing, but it is hard for patients to get to a pool
        every day.  Water exercise can be useful to get patients
        started when they can't tolerate anything else.  Once their
        stamina improves, they should add another form of exercise on
        the days they don't swim.  Exercise is most effective if done
        in the late afternoon or early evening, perhaps because of its
        known effect on deep sleep.  A small percentage of patients can
        never get up to an effective amount of exercise, but without
        it, few will improve much in my experience.  Patients who have
        been exercising daily and then skip a day will usually complain
        of feeling worse for 2-3 days afterward, an experience which
        often helps convince them of the need for daily exercise.
        Getting adequate sleep is essential.  FMS symptoms often appear
        during times of sleep disruption (Saskin 1986) such as may be
        brought on by an injury or other pain, stress, shift work, or
        having to get up to attend to young children.  At times just
        re-establishing a regular sleep schedule may be enough to
        relieve symptoms.  I have not been able to get patients who
        swing shifts to improve substantially unless they can get onto
        shifts that allow them to sleep nights and keep a consistent
        bedtime.
        Other coexisting sleep disorders such as obstructive sleep
        apnea (OSA) and periodic limb movements of sleep must be
        identified and treated.  Not infrequently a spouse's snoring
        will exacerbate the patient's symptoms, in which case treating
        the spouse's snoring or having the patient wear ear plugs will
        help.  44% of men with FMS have been found to also have OSA
        (May 1993), a potentially life-threatening disorder which is
        important to treat in its own right.  It is important to take a
        sleep history in all patients with FMS, including asking the
        spouse about snoring, apneas, and movements at night.  In
        resistant FMS cases, referral to a sleep disorders center for
        polysomnography may be helpful.
        Patients must also be careful not to overdo physical activity.
        For example, once she is feeling better a FMS patient may try
        to catch up on housework she has been unable to do, but this
        may trigger a relapse that puts her in bed for several days.
        It is better to plan to spend a smaller amount of time every
        day at such activities until they are completed.  Patients must
        learn to sense when they have reached their limit and stop
        before they get into trouble.
        Other treatment modalities which have been shown in controlled
        studies to be helpful include EMG biofeedback (Ferraccioli
        1989), regional sympathetic blockade (Bengtsson 1988), and
        cognitive behavioral therapy (Goldenberg 1991).  Many patients
        report that gentle massage as well as heat and rest help.
        Some report that, as with migraine, certain foods appear to
        precipitate their symptoms.  Several patients have told me that
        their FMS symptoms improved significantly on a low-fat weight
        reduction diet started to lose the weight gained from taking
        amitriptyline.  Most patients do better if they give up
        caffeine and other stimulants entirely.  Alcohol should be
        avoided because of its tendency to suppress deep sleep.  This
        is usually not a problem because most FMS patients tolerate
        alcohol poorly to begin with.  Certain symptoms such as
        migraine headaches or depression can also be treated directly
        if treatment of the underlying disorder does not control them
        adequately.
        FMS and myofascial pain syndrome (MPS), while probably separate
        entities, often coexist (Granges 1993).  When they do, each
        needs to be treated separately.  MPS is associated with trigger
        points which should be distinguished from the tender points of
        FMS.  Trigger points are located over a band of taut muscle and
        cause pain that radiates away from the point of pressure.  MPS
        is usually treated with avoidance of activities which worsen
        it, myofascial release and other forms of physical therapy, and
        if necessary, trigger point injections or dry needling.
        Support and education are important.  Patients need to be
        actively involved in their treatment and to have as clear an
        understanding of this complicated disorder as possible.
        Patients often elicit less sympathy and support from family,
        friends, and employers than they deserve because of the lack of
        physical stigmata of disease.  By the time they get to see
        someone skilled in the management of FMS, many patients will
        have been told by at least one other physician that there is
        nothing wrong with them or that it is "all in your head" which
        can be quite demoralizing.  An understanding approach by the
        physician and the patient's participation in a well-run support
        group may have considerable therapeutic benefit.
        Education, frequent follow-up visits, and reassurance help to
        get patients over the first few weeks of treatment.  It may be
        difficult to convince patients to exercise when they experience
        fatigue and aching.  It often takes two weeks or more before
        the beneficial effects of medication and exercise outweigh
        their side effects.  Sometimes it takes several months of
        trying different medications in different combinations and
        adjusting doses before getting it right.  The physician should
        check on the amount and type of exercise and sleep at return
        visits and reinforce their importance.  Patients should be
        warned that despite optimum treatment and good initial results,
        brief relapses are common, often caused by temporary sleep
        disturbances.  The patient will do best if she "gives in to
        it", takes hot baths, and tries to get extra rest during a
        relapse.  A temporary increase in medication dose may also be
        necessary.
        A small number of patients continue to do poorly despite
        treatment.  Severely affected patients who can't be controlled
        otherwise (treatment failures) need to be involved in a chronic
        pain program, as outpatients or if necessary inpatients.  Some
        may need to apply for disability, which is harder to get for
        patients with FMS because of the lack of supporting physical or
        laboratory evidence, but guidelines are available (White 1995).
        With treatment however, the majority who were working can
        return to work although some may need to change jobs or get off
        shift work.  Most patients referred to me as treatment failures
        had not had an adequate trial of treatment.
    Conclusion
        FMS is a common, chronic, and if untreated, often disabling
        disorder of unknown etiology associated with neuroendocrine and
        immunologic changes and disordered deep sleep.  Most patients
        can be helped with a combination of medication, exercise, and
        maintenance of a regular sleep schedule.  Think of this
        condition in any patient with a complaint of aching and
        tiredness and look for associated symptoms and tender points to
        confirm the diagnosis.  The common misconceptions that FMS is a
        psychosomatic or somatoform disorder, is untreatable, is a
        diagnosis of exclusion or a "wastebasket" diagnosis, and that
        most FMS patients are hypochondriacs or whiners are unfounded.

        Table 1:  Some drugs useful in the treatment of FMS
        Drug name            Starting     Taken __ hrs  Usual maximum
                               dose (mgs)   before bed    dose (mgs)
          trazodone              50           0            600
          cyclobenzaprine        10           1             60
          alprazolam              0.5         .5-1           6
          carisoprodol          350           0-.5        1400
          diphenhydramine        50           .5-1         300
          5-hydroxytryptophan   100           1            600
          amitriptyline           5           2            300

        Table 2: Associated signs and symptoms (Wolfe 1990).
            widespread pain                         97.6% of patients
            tenderness in > 11/18 tender points     90.1
            fatigue                                 81.4
            morning stiffness                       77.0
            sleep disturbance                       74.6
            paresthesias                            62.8
            headache                                52.8
            anxiety                                 47.8
            dysmenorrhea history                    40.6
            sicca symptoms                          35.8
            prior depression                        31.5
            irritable bowel syndrome                29.6
            urinary urgency                         26.3
            Raynaud's phenomenon                    16.7
        Other commonly reported symptoms include dizziness, trouble
        with memory and concentration, rashes, and chronic itching
        (unpublished observations).

        Table 3: Location of tender points (Wolfe 1990).
            suboccipital muscle insertions at occiput
            lower cervical paraspinals
            trapezius at midpoint of the upper border
            supraspinatus at its origin above medial scapular spine
            2nd costochondral junction
            2 cm distal to lateral epicondyle in forearm
            upper outer quadrant of buttock
            greater trochanter
            knee just proximal to the medial joint line
        To meet ACR 1990 diagnostic criteria for fibromyalgia, digital
        palpation with an approximate force of 4 kgs. must produce a
        report of pain in at least 11 of these 18 tender points.  Other
        areas can be tender as well.  The tenderness should be focal
        rather than diffuse.  Tender points must be present on both
        sides of the body, above and below the waist and in the midline.
        Widespread pain must have been present for at least 3 months.
        Some accept a diagnosis of fibromyalgia with fewer than 11
        tender points if several associated symptoms from table 2 are
        also present (Wolfe 1989).

        References:

        Baldessarini RJ.  Drugs and treatment of psychiatric disorders.
            In: LS Goodman and A Gilman eds., The pharmacologic basis of
            theraputics.  7th ed., New York: MacMillan, p. 413, 1985.
        Bengtsson A, Bengtsson M.  Regional sympathetic blocade in
            primary fibromyalgia.  Pain 33:161, 1988.
        Bennett RM.  Beyond fibromyalgia:  ideas on etiology and
            treatment.  J Rheumatol 16(suppl 19):185, 1989.
        Bennett RM et al.  Low levels of somatomedin C in patients with
            the fibromyalgia syndrome: a possible link between sleep and
            muscle pain.  Arthritis Rheum 35:1113, 1992.
        Boland EW.  Psychogenic rheumatism: the musculoskeletal
            expression of psychoneurosis.  Ann Rheum Dis 6:195, 1947.
        Buchwald D et al.  The chronic, active Epstein-Barr virus
            infection syndrome and primary fibromyalgia.  Arthritis
            Rheum 30:1132, 1987.
        Campbell SM et al.  Clinical characteristics of fibrositis.
            I. A "blinded" controlled study of symptoms and tender
            points. Arthritis Rheum 26:817, 1983.
        Chase TN and DL Murphy.  Serotonin and central nervous system
            function.  Ann Rev Pharmacol 13:181, 1973.
        Crofford LJ et al.  Hypothalamic-pituitary-adrenal axis
            perturbations in patients with fibromyalgia.  Arthritis
            Rheum. 37:1583-1592, 1994.
        Dunne FJ and CA Dunne.  Fibromyalgia syndrome and psychiatric
            disorder.  Br. J Hosp. Med. 54:194-197, 1995.
        Ferraccioli GF et al.  EMG biofeedback in fibromyalgia syndrome.
            J Rheumatol 16:1013, 1989.
        Gowers WR.  Lumbago -- its lessons and analogues.  Br Med J.
            1:117, 1904.
        Goldenberg DL et al.  A randomized controlled trial of
            amitriptyline and naproxen in the treatment of patients with
            fibromyalgia.  Arthritis Rheum 29:1371, 1986.
        Goldenberg DL.  Psychological symptoms and psychiatric diagnosis
            in patients with fibromyalgia.  J Rheumatol 16(suppl 19):
            127, 1989.
        Goldenberg DL.  Fibromyalgia and chronic fatigue syndrome:
            are they the same?  J Musculoskel Med. 7:19, 1990.
        Goldenberg DL et al.  High frequency of fibromyalgia in patients
            with chronic fatigue seen in a primary care practice.
            Arthritis Rheum 33: 1132, 1990.
        Goldenberg DL et al.  The impact of cognitive-behavioral therapy
            on fibromyalgia.  Arthritis Rheum 34(suppl 9):S190, 1991.
        Goldenberg DL.  Fibromyalgia: treatment programs.  J Musculoskel
            Pain.  1(3/4):71, 1993.
        Goldenberg D et al.  A randomized, double-blind crossover trial
            of fluoxetine and amitriptyline in the treatment of
            fibromyalgia.  Arthritis Rheum 39:1852, 1996.
        Granges G, Littlejohn G.  Prevalence of myofascial pain syndrome
            in fibromyalgia syndrome and regional pain syndrome:  a
            comparative study.  J Musculoskel Pain 1(2):19, 1993.
        Hauri P, Hawkins DR.  Alpha-delta sleep.  Electroenceph Clin
            Neurophysiol. 34:233, 1973.
        Hobson JA. Sleep after exercise.  Science 162:1503, 1968.
        Jaeschke R et al.  Clinical usefulness of amitriptyline in
            fibromyalgia: The results of 23 N-of-1 randomized,
            controlled trials.  J Rheumatol 18:447-451, 1991.
        May KP et al.  Sleep apnea in male patients with the
            fibromyalgia syndrome.  Am J Med 94:505, 1993
        McCain GA et al.  A controlled study of the effects of a
            supervised cardiovascular fitness training program on
            manifestations of primary fibromyalgia.  Arthritis Rheum
            31:1135, 1988.
        Moldofsky HD et al.  Musculoskeletal symptoms and non-REM
            sleep disturbance in patients with "fibrositis syndrome" and
            healthy subjects.  Psychosom Med. 37:341, 1975.
        Moldofsky HD.  A chronobiologic theory of fibromyalgia.  J
            Musculoskel Pain 1(3/4):49, 1993.
        Moldofsky HD.  Sleep, neuroimmune and neuroendocrine functions
            in fibromyalgia and chronic fatigue syndrome.  Adv. in
            Neuroimmunol. 5:39-56, 1995.
        Nxrregaard J et al.  A randomized controlled trial of
            citalopram in the treatment of fibromyalgia.  Pain 61:
            445-9, 1995.
        Pellegrino MJ et al.  Familial occurrence of primary
            fibromyalgia.  Arch Phys Med Rehab 70:61, 1989.
        Russell IJ et al.  Treatment of primary fibrositis/fibromyalgia
            syndrome with ibuprofen and alprazolam -- a double-blind,
            placebo-controlled study.  Arthritis Rheum 34:552, 1991.
        Russell IJ et al.  Elevated cerebrospinal fluid levels of
            substance P in patients with the fibromyalgia syndrome.
            Arthritis Rheum 37:1593-1601, 1994.
        Russell IJ.  Neurochemical pathogenesis of fibromyalgia
            syndrome.  J Musculoskel Pain 4(1/2):61-92, 1996.
        Saskin P et al.  Sleep and post-traumatic rheumatic pain
            modulation disorder (fibrositis syndrome).  Psychosom Med
            48:319, 1986.
        Schroder HD et al.  Muscle biopsy in fibromyalgia.  J
            Musculoskel Pain 1(3/4):165, 1993.
        Simms RW et al.  Lack of association between fibromyalgia
            syndrome and abnormalities in muscle energy metabolism.
            Arthritis Rheum 37:801-807, 1994.
        Smythe H.  Fibrositis syndrome: a historical perspective.  J
            Rheumatol 16(suppl 19):2, 1989.
        Vestergaard-Poulsen P et al.  31P NMR spectroscopy and
            electromyography during exercise and recovery in patients
            with fibromyalgia.  J Rheumatol 22:1544-1551, 1995.
        Wallace DJ. et al.  Fibromyalgia, cytokines, fatigue syndromes,
            and immune regulation.  In: Advances in Pain Research and
            Therapy, JR Fricton and E Awad, eds., Raven Press, v.17:
            227-287, 1990.
        White KP et al.  Work disability evaluation and the
            fibromyalgia syndrome.  Semin Arthritis Rheum 24:371-381,
            1995.
        Wolfe F.  Fibromyalgia:  the clinical syndrome.  Rheum Dis Clin
            North Am. 15:1, 1989.
        Wolfe F et al.  The American College of Rheumatology 1990
            criteria for the classification of fibromyalgia: report of
            the multicenter criteria committee.  Arthritis Rheum.
            33:160, 1990.
        Wolfe F.  Fibromyalgia: on diagnosis and certainty.  J
            Musculoskel Pain 1(3/4):17, 1993.
        Wolfe F.  The epidemiology of fibromyalgia.  J Musculoskel Pain
            1(3/4):137, 1993.
        Wolfe F et al.  A double-blind placebo controlled trial of
            fluoxetine in fibromyalgia.  Scand J Rheumatol 23(5):
            255-9, 1994.
        Yunus MB et al.  A controlled study of primary fibromyalgia
            syndrome: clinical features and association with other
            functional syndromes.  J Rheumatol 16(suppl 19):62, 1989.
        Yunus MB et al.  Relationship of clinical features with
            psychological status in primary fibromyalgia.  Arthritis
            Rheum 34(1):15-21, 1991.

------------ end of document --------------------------------------

CONTROLLING PAIN IN FIBROMYALGIA SYNDROME

                by Camilla Cracchiolo, RN
Copyright 1996.
May be freely reproduced for non-profit purposes as long as credit is given.
In the US, all chronic pain conditions are seriously undermedicated.
Chronic pain conditions like FMS, certain kinds of low back pain, and
migraines, where there are not hard physical findings such as abnormal
X-rays, tend to be the most undertreated.  But the problem is not linited
to these conditions.  A recent study found that 1/3 of terminal cancer
patients were not prescribed proper pain medication and therefore did not
get relief.
In the study of cancer pain, three reasons were given by physicians for
why they had not prescribed more medication:
1) Despite the fact that these were *terminal patients in the last few
months of life*, physicians were afraid of creating an addiction.
2) The doctors were afraid of harrassment by the Drug Enforcement
Administration if they gave out too many narcotic prescriptions.  The DEA
keeps a very close eye on doctors, because a few rotten eggs have gone
into the 'prescription mill' business of providing narcotics for street
addicts.
3) The most common reason: physicians simply didn't ask their patients if
they were in pain.  They assumed that the patient would ask them if they
needed help.
This study also found that physicians often didn't prescribe the
medication correctly and that medications were often inappropriately
withheld by nurses (this isn't a rant only against doctors.
Unfortunately my own profession is also ill-informed.)
This study is alarming, because terminal cancer is a condition
where severe pain is expected.  Imagine, therefore, what other people in
pain must be facing.  And in fact, other studies have found similar
results, with pain relief in children being another problem area.
This, then, is the atmosphere in which a patient with FMS must seek
treatment.  But people with FMS have additional problems.  Often, we
have been complaining of pain for years.  Many of us who have had pain
that was more severe in one area such as the lower abdomen or low back
have seen many doctors and had countless tests to rule out serious
problems.  We may even have had unnecessary surgeries: women with FMS
have frequently had laparoscopies to find endometriosis.  Others of us
have been told that we had carpal tunnel syndrome or disorders of spinal
disks.  When treatment for these conditions don't work, or when nothing
is found on tests, physicians often stop believing that we have pain at
all.  Many times, people with FMS have been told that they are
hypochondriacs or just seeking attention and told to get psychiatric
help. Worse, some of us have been labelled as drug addicts and had our
medical records so marked.  Some of us have even been verbally abused by
physicians.
This leads to discouragement.  A lot of us have simply stopped talking to
physicians about pain, and try just to cope with it on our own.  But
don't give up!  It IS possible to get fair, even good pain relief, in
fibromyalagia syndrome.
First, you need a physician who knows about FMS and takes it seriously.
The best way to find a doctor knowledgable about FMS is to check
with your local FMS support group or ask for recommendations over on
alt.med.fibromyalgia (which is also the fibromyalgia mailing list;
they're gated.)  If you have no idea how to find a local support group,
you don't know how to find alt.med.fibromyalgia, or if you just don't
know much about fibromyalgia syndrome in general, I have a very *long*
FAQ I can send you by e-mail.
If you request it, I can also send you an article I wrote
called "Dealing With Doctors When You Have Chronic Fatigue Syndrome".
Even though the article is about CFS, the information is very applicable
to folks with fibromyalgia syndrome.  In it, I talk about how to get
physicians to take your condition seriously, how to get your medical
records, how to search medical databases, books you should buy and many
other things.
Often, rheumatologists are the doctors who take care of people with FMS
and generally they are pretty well informed.  You may also want to consult a
physician who specialzes in pain management if you haven't already.  Most
people with FMS seem to do best with a combination of therapies, which
may mean combining non-drug treatments with medications, or combining
several different kinds of medications or both.  Pain specialists have
access to not only many drugs but also to many non drug therapies as
well.  If you can find one who is knowledgable about FMS, pain
specialists can be quite helpful in developing a multi-factor
treatment.  Usually you need a referral from another physician to see a
pain management specialist.

Moving on to treatments:
NON-DRUG TREATMENTS: You're probably familiar with many of these,
since most people with FMS have in desperation tried every single thing
they can lay their hands on.  This catagory includes spray and
stretch; more traditional physical therapy like hot packs,ice packs,
diathermy, electrical muscle stimulation and/or TENS; massage; yoga or
other stretching exercises; Feldenkrais body work (which
helped me a lot, BTW), acupuncture, biofeedback, exercise in water and
aerobic exercise. I'm not going to address every single one: hot packs,
ice packs and massage, for example, are fairly self-explanatory and people
are able to explore them on their own.  (and no doubt already have.)
But I do want to address some of these treatments.
Spray and stretch:  This treatment involves spraying the skin with a
   local anesthetic and then a physical therapist stretches the muscle while
   it's numb.  It can be very helpful if you have areas of spasm in the
   middle of muscles.  You can feel these: they feel like big knots or bands.
Cranio-sacral release: a special kind of physical therapy that stretches
   the back and neck muscles.  Very good for breaking up spasms in the
   neck and low back.
Yoga and stretching:  They key words here are 'gentle' and 'gradual'.
   Yoga and other kinds of stretching are very helpful in FMS but if you
   don't proceed carefully and slowly, you can cause more pain.
Feldenkrais movement therapy:  Feldenkrais is a kind of gentle movement
   therapy.  Usually, one learns the technique in a class, but Feldenkrais
   practitioners also offer private sessions where they passively move your
   joints in certain specific ways.  Many people with FMS rave about how
   great Feldenkrais is, and I'm one of them.  It was the first treatment I
   ever found that would give me relief for weeks instead of hours.
   Unfortunately, unless you can find a Feldenkrais practitioner who works
   with a physical therapist (or in some places, a chiropractor), insurance
   does not pay for it and private sessions can be *quite* expensive.
   Feldenkrais practitioners believe that the kinds of movements they do
   create new patterns in the brain.  It has never been studied, but I
   suspect this is untrue.  However, Feldenkrais definitely has a place in
   physical therapy.
Acupuncture and Traditional Chinese Medicine (TCM):  Acupuncture has been
   shown scientifically to be effective in controlling pain.  However, most
   researchers don't accept the explanation TCM practitioners invoke, which
   involves 'body energies' such as chi (also called Qi.)  Most researchers
   believe that it works by affecting the central nervous system, when in
   turn then releases natural pain killing substances called endorphins.
   But nobody is really sure what's going on.  One very interesting
   finding in FMS research is that inserting dry needles into trigger points
   is almost as effective as injecting those points with anesthetic or
   anti-inflammatory drugs.  Whatever the cause, some people with FMS do
   well with it.
   TCM practitioners are also trained in the use of herbs and often suggest
   herbal therapies to their patients.  Many of these herbs contain powerful
   pharmacologic agents and have not been adequately studied.  The
   effectiveness of herbal therapy in FMS has never been scientifically
   studied.  Herbal medicine presents special problems to the person who
   wishes to use it.  Persons who wish to experiment with herbal therapies
   should be very well read and informed about all the issues before
   proceding.  I have an article called "CAUTIONS ABOUT HERBAL MEDICINE"
   which I can send to you if you send a message to camilla@primenet.com
Aerobic exercise:  Many people with FMS report that very careful,
   gradually built up aerobic exercise, combined with the use of medications
   that help sleep, provide them with significant pain relief.  However,
   this is controversial among that segment of people with fibromyalgia
   syndrome who also have Chronic Fatigue Syndrome.  Many people with CFS
   report serious exacerbation of their illness when attempting exercise.
   Studies conflict: one study has suggested that aerobic exercise is
   beneficial to people whose illness is mild and who are relatively high
   functioning.  Others have suggested that reconditioning is not possible
   in CFS.  Still others have expressed great concern that physical
   deconditioning worsens CFS, creating a vicious cycle. The issue is
   not resolved.  People with CFS should proceed very slowly in
   attempting any conditioning program. Exercise in a swimming pool has
   been reported helpful by a few people with CFS who could not otherwise
   tolerate an exercise program.

THINGS TO AVOID OR USE ONLY WITH CAUTION:
Rolfing:  Rolfing is a kind of very deep, very painful massage.  Every
   person with FMS that I have spoken with who tried this said that it
   caused severe worsening of their symptoms.
Chiropractic:  Chiropractic has been shown to be more effective than
   placebo in treating low back pain, and probably in mid-back pain as
   well.  I have used it for that purpose.   But I now have reservations
   about the use of chiropractic adjustment in FMS.  Many people with FMS
   have hyper-mobile joints, and one theory of FMS is that the pain comes
   from all the extra work that our muscles have to do to keep our body in
   alignment.  Since chiropractic increases joint mobility, it may be
   counterproductive in the long run.
   Many chiropractors also don't want to limit themselves to the treatment
   of back pain.  The basic theory of chiropractic, that 'subluxation' of
   the spine causes numerous medical disorders, has been proven false.  Many
   engage in practices of no scientific merit such as testing for
   allergies by muscle tension (kinesiology) or sell supplements of
   questionable value.  Chiropractic neck adjustments can be dangerous
   in a small percentage of people, causing stroke via tearing of the
   vertebral artery.  If you decide to try chiropractic, avoid
   chiropractors who engage in such practices.
Echinacea:  Echinacea is an herb believed to stimulate the immune
   system.  Many people use it to ward off colds or the flu.  I use it for
   that purpose without problems, although I use it sparingly and only for
   short periods. Some people with Chronic Fatigue Syndrome have been
   experimenting with it, since an unknown percentage of people with CFS
   have an associated immune deficiency.  A few find that it helps with
   the sore throat and swollen lymph nodes in the neck associated with
   the illness (particularly if used in liquid form and held in the
   mouth for a bit before swallowing).  However, it is also believed
   that many of the symptoms of CFS (and therefore perhaps of FMS since
   the illnesses appear to be related) are due to high levels of immune
   stimulating chemicals in the blood.  There are anecdotal reports of
   echinacea worsening fatigue and causing body aches.

DRUG THERAPIES: these include anti-depressants, medications to improve
sleep, muscle relaxants and various pain drugs.
Anti-depressants:  Many physicians consider anti-depressants
  the first choice medication for FMS because they are non-addicting and
  useful in treating sleep problems.  Unlike sedatives such as
  barbiturates, they don't interfere with the deep levels of sleep so
  important in properly controlling fibromyalgia pain.  Some
  anti-depressants also have pain control properties because they can
  block pain impulses high in the spinal cord (particularly the SSRIs
  like Prozac and Zoloft, and amitriptyline, which is a tricyclic.)
  These effects are independent of their effects on depression and these
  anti-depressants are often used in the treatment in pain of
  neurologic origin.  Many physicians feel that FMS pain originates in the
  central nervous system, via dysregulation of the normal pain perception
  mechanisms in the brain and high in the spinal cord.  So, if your
  physician suggests an anti-depressant, it doesn't necessarily mean that
  he/she thinks it's all in your head.
  The side effects of antidepressants can be very annoying, however.  The
  SSRIs have fewer side effects than the others, but are not very helpful
  in promoting sleep.  The heterocyclics and tricyclics help sleep but
  often produce sedation, brain fog, weight gain and dry mouth.  Both the
  SSRIs and the heterocyclics are associated with sexual dysfunctions in
  about 1/3 of their users.  I'm working on an article on sexual
  dysfunction in CFS that will address some of these medication
  issues.  If you send an e-mail request to camilla@primenet.com, I'll
  send you a copy when it's finished.  (note: you may wait a long time,
  since my own CFS does not permit any deadlines.)
Sleep meds:
Like most people with FMS, I have the 'Sleep Disorder from Hell'.
Treating my sleep has not cured my fibromyalgia but it has definitely made
my life more bearable.  With all the drugs bedlow there is  a tradeoff:
you may sleep better but find that you are more groggy in the morning.
If you happen to be one of the folks with FM/CFS and Neurally Mediated
Hypotension (NMH), these drugs can lower your blood pressure.  You may not
be able to take them, in that case, although you may be able to fix this
by adjusting the dose of Florinef or whatever drug you normally take for
this problem.  Dose adjustment for NMH should be done, of course, only
with the close and careful supervision of an M.D.
Antidepressants particularly effective in sleep disorders are Desyrel
   (trazadone) and Elavil (amitriptyline).
Antihistamines (dimenhydramine, chlorpheniramine, Atarax):  These are
   supposed to not interfere with the deeper sleep stages, although I
   find that when I rely on them alone (with no prescription sleep aids),
   they knock me out but I wake up after 4 hours no matter what. But some
   people with FMS do quite well with them.  Atarax is a prescription
   drug; however over the counter antihistamine sleep aids like dimenhydramine
   (benadryl, Sominex, Nytol) and chlorpheniramine (Chlor-Trimeton)
   probably work just as well and are cheaper.  When combined with my
   regular sleep meds (amitriptyline and Klonopin), they add an extra
   punch that I find useful.  I find increasing the antihistamines  to be
   preferable to my other option, which is to increase the Klonopin.
   Since Klonopin in quite addictive and tolerance can build up quickly, I
   try to Klonopin dose under 1 mg.  Antihistamines also improve
   my sleep by keeping my nasal passages clear and hence cutting down on
   snoring. These drugs are usually safe to take with prescription meds.
   (although you should NEVER combine prescription and non-prescription
   drugs without first  checking with the doctor who prescribed you the
   drug).
   If you decide to try antihistamines, make sure that you don't
   use any kind of combination product, particularly one which says
   'decongestant'.  Decongestant = pseudoephedrine (Sudafed) = stimulant,
   which equals staying up all night, guaranteed.  Plus, unlike
   antihistamines alone, pseudoephedrine has dangerous interactions with a
   number of antidepressants and can elevate blood pressure and cause
   abnormal heart rhythms.
   Note: you may need to exceed the maximum dose on the label to get
   results.  Up to twice the standard dose is fairly safe, but you should
   check with your physician before doing this. You may also find that you
   do better by taking more than one antihistamine at night.  I currently
   take a long acting version of chlorpheniramine called Effidac, which
   acts for 24 hours, plus 12 mg of regular short acting chlorpheniramine
   in addition to my prescription meds.  When this still doesn't work, I
   add 50 mg of benadryl.  At high doses, it's possible to develop
   urinary retention, so men with enlarged prostates or folks who have
   other problems with the urinary tract should keep this in mind.
Benzodiazepines (Valium, Xanax, Klonopin):  For getting to sleep, I find
   that Klonopin (which is a benzodiazepine but also an anticonvulsant)
   knocks me right out and is the best thing I've ever found for those
   nights when I just can't get to sleep no matter what.  Unfortunately,
   all benzodiazepines can interfere with the deeper stages of sleep, so
   they're probably not the best first line choice.  They're also
   addicting and tolerance can build up pretty fast, so I use Klonopin
   only sparingly.
Valerian root: This herb has been used for decades in Europe for the
   treatment of occasional insomnia and as a mild tranquillizer.  It is
   well studied and appears to act on a neurotransmitter called GABA,
   which is responsible for 'turning down' brain reactions:
   benzodiazepines and other tranquillizers act on this same system.
   Nobody knows exactly what the active ingredient is, although high on
   the list of suspects are some chemicals called 'valproates', which are
   cousins to a prescription anti-convulsant called valproeic acid.
   (For the record: the drug diazepam (Valium) is NOT extracted from
   valerian.  This is a common myth about valerian.  Valium and valerian
   have no relationship to one another.)

   There are many researchers and physicians in the US, including some
   very conservative 'quack busters' who think that valerian should be
   approved as an over the counter sleep aid here in the U.S.
   Valerian is good for occasional use and I take it on top of my
   other meds as a last resort when I can't get to sleep. I don't
   recommend valerian for constant use for the following reasons:
   1.  Its effects tend to wear off over time.
   2.  It can improve depression in the short run, but may cause or
   aggravate depression when used every night for several months.
   3.  It failed the Ames test, which is the standard test to see if an
   agent can cause cancer or birth defects.  Many useful substances have
   failed the Ames test but don't appear to cause cancer in humans.
   However, I would not take it regularly or give it to children for this
   reason. Since the Ames test measures the rate at which a given
   substance causes mutations in bacteria, failing the test means that the
   substance may cause birth defects in addition to cancer.  I strongly
   urge that it NOT be used by pregnant women.
   For more information, see the following files on my web site: the
   valerian article by herbalist Fred Shaw, the Herbal Products
   Proposed Regulation from the National Council Against Health Fraud,
   and my article: "Herbal Medicine: Often Helpful But Use With Care"

Pain medication options include:
Muscle relaxants:  This is often another way of saying 'benzodiazepine'
  (see sleep med section above.)  However benzos can be helpful in
  dealing with muscle spasms.  There is also an anti-depressant called
  Flexeril that many people with FMS find helpful because it has genuine
  muscle relaxant effects.  This catagory also includes carisoprodol
  (Soma, Rela) which basically metabolizes to a tranquillizer called
  meprobamate.  Meprobamate is addictive; however carisoprodol does have
  muscle relaxant effects via the central nervous system and so may be
  helpful to some people with FMS.
Trigger point injections:  Some people find that injecting anesthetics,
   opiates and/or anti-inflammatories like cortisone directly into those
   big knots we get is helpful.  Some people also advocate this for
   tender points (no lump, just sore) as well.  However, it's not clear
   whether the big benefit is from the medication or from the needle.  At
   least one study has found inserting a dry needle, minus medication, to be
   almost as effective in relieving pain.  So I suppose this could be
   included in non-drug therapies as well.  And acupuncturists just love to
   stick needles into tender points.  :)
NSAIDS (Ibuprofen, Naproxen, salcylates): These are not real effective
   for lots of folks but help me out sometimes.  I find that for some
   reason they work better for me when the pain is localized to one area.
   They don't seem to help much when I have that 'hurt all over' kind of
   pain.
Stimulants:  A few people seem to be getting good pain by combining two
   mild stimulants called phentermine and fenfluramine.  I don't
   agree with the explanation for it's actions given by the main physician
   promoting it but some people swear by it, and I'm not going to try to
   talk anyone out of something that really works for them. The drugs are
   not particularly dangerous for most people, are less addicting than many
   of your other options and might be worth a try.  However,
   fenfluramine is associated with an extremely rare but life
   threatening illness called pulmonary hypertension.  More information
   on this topic is available at my website in the article titled:
   "Phentermine/Fenfluramine and Pulmonary Hypertension". Phentermine
   and fenfluramine  may aggravate sleep problems.  A theoretical concern with
   fenfluramine is that it has been shown to decrease the # of serotonin
   receptors in rat brains when used for a long time.  This might cause
   or worsen depression in humans; however no human studies on this are
   available at this time.
   To throw in some personal experience: I've taken  phentermine but not
   fenfluramine.  I find that I am very sensitive to even small doses of
   phentermine, that I have more energy for a while, and certainly eat less
   (a big plus, let me tell you); however, I can't take them every day,
   because it appears to build up in my system and it starts interfering
   with my sleep: it also increases my blood pressure by about 10 mm Hg
   and markedly aggravates my brain fog.  For what it's worth, I haven't
   let that stop me from taking the drug but it's something to keep in
   mind.
Tegretol (generic = carbamazepine).  This is an anti-convulsant drug
   with pain relieving properties that's often used to treat a
   severe facial pain disorder called trigeminal neuralgia.  It's never
   been studied for FMS pain.  I stumbled upon its effect on FMS pain quite
   by accident, when I tried it to see if it would relieve some of my
   brain fog.  Unfortunately, the effect seems to have worn off,
   although it worked pretty well for me for over a year.  The most
   common side effect is the development of an itchy rash when exposed to
   sunlight.  It also can (rarely) cause serious blood disorders and it can
   be toxic in high levels.  Your doctor should monitor the blood level and
   periodically run a complete blood count if you are using this drug.
Ultram (tramadol): Some people with FMS swear by it.  It has the
   advantage of not producing the buzz associated with opiates and
   benzodiazepines.  This can be a big plus with people who have brain
   fog.  Ultram was originally promoted as a non-addicting
   alternative to opiates.  However, a number of cases of addiction have
   now been reported in the literature, so this is no longer considered
   true, although it may prove less addictive than opiates: the jury is
   out on that.  Tolerance appears to develop pretty quickly and people
   *definitely* go through withdrawal when they get off it.  It also
   causes nausea in a significant percentage of people. Myself, I found
   that even taking 100 mg. of Ultram three times a day didn't help my
   FMS pain nearly as well as 1 Tylenol #3 at night, although I also
   didn't have the nausea often associated with it.
Opiate narcotics: The last resort and, in my opinion, not used nearly enough
   to treat FM pain.  But use with caution.  Many people try to reserve
   narcotics for really bad flare-ups and rely on the other methods listed
   above for routine pain control. I personally have managed to avoid the
   heavier narcotics like Vicodan, Demerol and Percoset; but Tylenol #3
   and #4 (containig 30 mg and 60 mg of codeine respectively) provide the
   best pain relief for me of everything I've ever tried.  Many other
   people with FMS say the same thing: narcotics work when all else
   fails.  Right now, I use Tylenol #3 about twice a week, when the
   pain is so bad that I can't sleep.
   Alas, narcotics are *very* addicting, and tolerance can build up
   quickly; although  contrary to popular opinion FM pain can
   certainly be bad enough to warrant their use.  Drug addiction is a bad
   enough thing that doctors are legitimately quite worried about
   addicting people to narcotics and hence creating an even worse
   problem than the pain.  It's no fun trying to clean up the mess that
   an addiction, even to legal substances, usually leaves.  Narcotics can
   also interfere with your life even you're not addicted.  They can
   produce a lot of brain fog, a drawback if you have to hold a steady job
   or drive a car, or even be in the here and now.  This means that you
   may have a hard time getting them out of your doctor if you decide
   you want to try them for more than very occasional use or find
   that only heavy narcotics relieve your pain.
   Numerous studies have shown that chronic pain patients, with a legitimate
   need and who are under careful medical supervision, do not engage in
   addictive behaviors even when prescribed strong narcotics for long
   periods of time.   One reason I urge people with FMS to try to find a
   good MD who specializes in pain management is, not only do these
   people have a wide arsenal of non-drug therapies, but they are the
   docs most likely to be aware of all the recent research on pain and
   narcotics.  Of all physicians, they are the most likely to take pain
   complaints seriously and to prescribe narcotics when appropriate.
   They are also the people most likely to prescribe narcotics correctly
   (which is to use high doses to get the pain under control fast and
   then use small but regular doses to keep it that way.)

   "The trick is to keep an open mind, without it being so open
                      that your brain falls out."
                        Camilla Cracchiolo, RN
    camilla@primenet.com            http://www.primenet.com/~camilla

            By Jenifer Joseph
            ABCNEWS.com

            April 8 - Jan Murphy committed suicide last
            summer because she could no longer live with a
            disease that many doctors still don't believe exists.
                 She had fibromyalgia, a chronic pain condition that made
            a cool breeze on her skin feel like fire and caused every part
            of her body to ache. After CT scans and MRIs showed no
            medical reason for her pain, Murphy turned to Dr. Jack
            Kevorkian for a final solution.
                "When you start hearing there is no hope, no treatment,
            and no cure, over and over, you lose your will to fight,"
            Murphy wrote in a eulogy that was read at her funeral. "What
            most people saw of me was a shell of what was going on
            inside."