Pathogenesis of Fibromyalgia
Role of Stressors Once fibromyalgia develops, the mechanisms responsible
for ongoing symptom expression are likely complex and multifactorial. Because of
the fact that disparate "stressors" can trigger the development of these
conditions, the human stress response has been closely examined for a causative
role. These systems are mediated primarily by the activity of the
corticotropin-releasing hormone (CRH) nervous system located in the hypothalamus
and the locus-ceruleus-norepinephrine/autonomic (sympathetic/LC-NE) nervous
system in the brain stem. Recent research suggests that although this system in
humans has been highly adaptive throughout history, the stress response may be
inappropriately triggered by a wide assortment of everyday occurrences that do
not pose a real threat to survival, thus initiating the cascade of physiologic
responses more frequently than can be tolerated.[26]
The type of stress and the environment in which it occurs also have an impact
on how the stress response is expressed. It has been noted that victims of
accidents experience a higher frequency of fibromyalgia and myofascial pain than
those who cause them, which is congruent with animal studies showing that that
the strongest physiologic responses are triggered by events that are accompanied
by a lack of control or support, and thus viewed or perceived as inescapable or
unavoidable.[27] In humans, daily "hassles" and personally relevant stressors
seem to be more capable of causing symptoms than are major catastrophic events
that do not have a personal impact on the individual.[28,29]
Genetic differences also play a role in the expression of the biologic
response to stress, as well as in the systems that process sensory information.
Data collected from animal studies show there are inter- and intraspecies
differences for the "set points" for these systems. Set points may be
permanently altered by repeated exposure to environmental stressors. Certain
studies in animals have indicated that early-life traumas are particularly
likely to have a permanent effect on the animal's biologic response to
stress.[26,30] This notion is supported by data indicating that patients with
many of the conditions may be more likely than nonaffected individuals to have
experienced physical or sexual abuse in childhood, although these retrospective
studies are methodologically problematic.
Role of Neuroendocrine Abnormality The theoretical links between neural
stress systems and symptom expression have generally been supported by studies
demonstrating alterations of the hypothalamic-pituitary-adrenal (HPA) axis and
the sympathetic nervous system in fibromyalgia and related conditions.[31-35]
The best way to summarize these findings is that there is hyperactivity of both
the hypothalamic pituitary adrenal axis and the sympathetic nervous system in
individuals with fibromyalgia and related conditions. However, no consistent HPA
or autonomic abnormality can be found in the majority of patients with this
spectrum of illness. Moreover, recent work suggests that rather than these
abnormalities being directly responsible for symptoms, they may represent a
"diathesis" that predisposes individuals to develop these symptoms. For example,
results from a recent study[36] suggest that depriving individuals who exercise
regularly of their normal routine (as may occur if
an individual decreases usual activities after any number of the "stressors"
that are capable of triggering fibromyalgia) may lead to symptoms such as pain,
fatigue, and mood disturbance. After 1 week of exercise cessation, 8 of 18
subjects in the study developed worsening pain, tenderness, fatigue, or mood
symptoms. Stress response system function may identify those individuals
particularly vulnerable to the development of such symptoms, as the affected
subjects in the study had significantly reduced baseline HPA axis activity and
autonomic nervous system function compared with those who did not develop the
symptoms.
Alternatively, altered neuroendocrine axis activity could cause or occur as a
consequence of some fibromyalgia symptoms. It is likely that these
neurobiological alterations are shared with other syndromes that are known to be
associated with HPA and/or autonomic function, such as depression or
posttraumatic stress disorder (PTSD). Figure 3 illustrates a model of
susceptibility and development of these disorders that takes into account both
genetics and personality as risk factors.
Figure 3. The hypothesized relationship between "stressors" and the
development of syndromes such as fibromyalgia, PTSD, and depression. The model
in Figure 3 recognizes the critical importance of stressors in "resetting stress
response systems," as well as other factors, including:

the role of behavioral adaptations to these stressors, such as cessation of
routine exercise; and
whether an individual is in an environment characterized by control or
support.




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