Subgroups in Fibromyalgia
Pain
Amplifying Neurochemical Mechanisms in
Fibromyalgia Syndrome (FMS)
I. Jon
Russell, M.D., Ph.D.
The University of Texas Health Science Center
San Antonio, Texas, USA
OBJECTIVE:
The goal is to present what is known, and to project what is likely to
be found, regarding the role of neurochemicals in the pain amplification
processes responsible for the symptoms of FMS.
METHODS:
The main sources of information are the published medical literature,
but some unpublished data will also be highlighted. The proposed
pain amplification mechanisms are based on current knowledge about nociception
states, such as allodynia. Considered will be excessive pronociceptive
(agonist) activity and deficient antinociceptive (antagonist) activity.
RESULTS:
The presence of widespread body pain in FMS earlier prompted our hypothesis
that central systemic processes might be responsible. The most dramatic
and consistent biochemical finding to date has been an elevated level
of substance P (SP) in FMS spinal fluid (CSF). Statistical correlations
of pain measures with CSF SP levels or of changes in CSF SP levels with
elapsed time have both supported the hypothesis that SP contributes to
the pathogenesis of FMS. The production of CSF SP can be enhanced by ongoing
peripheral pain, by elevated CSF nerve growth factor, or by elevated levels
of CSF dynorphin A. All of these abnormalities have been documented in
primary FMS. Failure of antinociception could result from low levels of
metenkephalin, norepinephrine, or serotonin. All of these have been observed
in FMS. The key event responsible for the onset of FMS is unknown but
it could relate to spinal cord injury from a variety of processes, such
as Chiari malformation, syringomyelia, or cervical spinal cord injury
wit whiplash. CSF SP levels in FMS correlate with decreased brain regional
blood flow. Spinal cord levels of SP are elevated below the level of syringomyelia
spinal cord lesions. Many other bodily functions, such as the abnormal
bowel motility associated with irritable bowel syndrome, are known to
be influenced by these same neurochemical mediators. It is reasonable
to predict that the distinction between FMS and other troublesome clinical
syndromes, such as chronic fatigue syndrome, irritable bowel syndrome,
or even major depression may relate to subtle differences in the relative
concentrations of potent neurochemicals
Conclusions: The widespread
body pain and tenderness which characterize FMS could result from central
pain amplification mediated by the neurochemicals of nociception. Abnormalities
in FMS brain regional blood flow, neuroendocrine function, autonomic neural
function, and intestinal dysmotility could all result from imbalances of
the same neurochemicals within the central nervous system. Presented
at the National Fibromyalgia Research Association's Subgroups in Fibromyalgia
Symposium, September 26-27, 1999, in Portland, Oregon.
