Fibromyalgia

John Winfield, MD
University of North Carolina at Chapel Hill School of Medicine
Fibromyalgia is a syndrome characterized by generalized pain,
fatigue, disturbed sleep, and numerous unexplained somatic complaints
that is present in at least 5% of the general adult population
(mostly women) in Western countries. With the exception of painful
tender points, the clinical, routine laboratory, and imaging
evaluations in uncomplicated fibromyalgia are normal, which has led
some to assert that this syndrome either does not exist or is
strictly a psychological disorder. Fibromyalgia largely overlaps with
chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS),
temporomandibular joint pain, "myofascial pain syndrome," and other
regional pain syndromes. Best classified at the present time as one
of a series of "symptom-based conditions" or "functional somatic
syndromes," recent research in the neurophysiology and
neuroendocrinology of pain demonstrates that fibromyalgia is not
simply a psychological disorder.

Pain, the hallmark of this syndrome, diffusely radiates from
the axial skeleton and is localized to muscles and muscle-tendon
junctions of the neck, shoulders, hips, and extremities. Pain
thresholds are reduced, and many patients exhibit generalized
allodynia, defined as pain from normally nonpainful stimuli. Although
depression, anxiety, and other psychiatric comorbidities are commonly
present, the pain and fatigue associated with fibromyalgia have
demonstrable pathophysiologic bases.

At one level, fibromyalgia can be viewed from the perspective
of Engel's biopsychosocial model of chronic illness.1 According to
this model, pain, fatigue, and other symptoms arise and persist from
an interplay of a series of biologic, psychological, and sociologic
variables. Gender, poor sleep, neuroendocrine and autonomic
dysregulation related to chronic stress, and abnormal processing of
afferent input to the central nervous system have clearly been
identified as important biologic variables. The most dramatic
laboratory abnormality is a consistently elevated level of substance
P in the cerebrospinal fluid, which is found in about 80% of
fibromyalgia patients. Social and behavioral research is providing
crucial insight into the role of cognitive-behavioral variables, such
as pain beliefs and attributions, depression, anxiety and perceived
self-efficacy for pain control, and environmental and sociocultural
variables, such as a history of childhood sexual abuse, which appears
to be a particularly important antecedent.

Evidence for therapeutic efficacy in fibromyalgia based on
randomized, controlled trials has been difficult to obtain because of
current poor understanding of etiopathogenesis, symptom complexity,
and lack of consensus regarding nosology and clinically meaningful
outcome measures. Consequently, much current treatment is based on
proposed, rather than established, models of pathophysiology.
Nevertheless, the available data clearly suggest that symptoms of
pain, fatigue, nonrestorative sleep, depression, and anxiety respond
to a multifaceted therapeutic approach combining pharmacologic and
nonpharmacologic (physical, psychological, and behavioral)
treatments. The goal is palliation of symptoms, not cure.

Abundant evidence from randomized, controlled trials supports
the efficacy of physical modalities, especially graded aerobic
exercise, various stress-management approaches, and judicious use of
pharmacologic agents. Conversely, many widely used nonpharmacologic
treatments (e.g., "trigger point" injections, botulinum toxin
[Botox], acupuncture, and ultrasound) have not shown significant
benefit beyond nonspecific, placebo-related effects. Sleep
disturbances should be treated aggressively, both by attention to
good sleep hygiene and by appropriate use of the many new hypnotic
and anxiolytic medications. Selective serotonin reuptake inhibitors
benefit both associated depression and the diffuse pain and other
symptoms in fibromyalgia. Persistent fatigue responds to modafinil
(FDA approved for narcolepsy) or tropisetron, a 5-HT3 receptor
antagonist. First-line agents for the diffuse pain in fibromyalgia
continue to be the low-dose tricyclic antidepressants (TCAs), often
in combination with a centrally acting muscle relaxant, such as
cyclobenzaprine. Marked allodynia and hyperalgesia often respond to
the addition of an antiepileptic drug, such as gabapentin or
pregabalin. Topical capsaicin also is useful when applied to painful
areas with gentle massage. Other drugs that have effects on the
abnormal central nociceptive processing in fibromyalgia include
mexilitine (sodium channel blocker), clonidine (centrally acting
antiadrenergic), and tropisetron. In rare cases, patients may require
opioids to improve quality of life and maintain daily functioning.

The prevalence of fibromyalgia, its impact on quality of life
and functional capacity, and its attendant personal and societal
costs impel the medical community to take this illness seriously.
Recent advances in our understanding of chronic "unexplained" pain
and its treatment provide optimism for the future.

1. Engel GL: The need for a new medical model: a challenge for
biomedicine. Science 196:129, 1977 [PMID 847460]