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 Why
can we not simply advance our understanding by studying patients
with persistent pain? Many prevalent pain diseases are "multi-factorial"
or "complex," which means that they cannot be attributed
to the mutation of a single gene or the effect of a single environmental
factor. Instead, these diseases develop from the combined action
of many genes, risk-conferring behaviors, and environmental factors.
Although valuable information can be obtained from the study of
clinical cases, such research is often compromised because the
sequence of events is unclear. The links between peripheral pathology,
central neurobiology, and the associated sensory, motor, autonomic,
mood, and cognitive signs and symptoms are unknown because all
these variables present at once (though with variation between
patients) and are, therefore, tough to parse. Discovering the
underlying mechanisms of signs and symptoms can be further complicated
by concurrent use of medications and other types of therapy. For
this reason, problem simplification using model systems is useful,
and such systems should be viewed as research tools for probing
complex mechanisms.
The study of model systems is an important beginning to the development
of mechanistic diagnoses and treatments. Human pain models such
as the use of noxious thermal and electrical pulses, intra-dermal
injection of the irritant capsaicin, intramuscular infusion of
saline, or third molar extractions are all valuable tools for
the exploration of the pathogenesis of poorly understood symptoms
and/or the often puzzling co-morbid ailments encountered in clinical
pain conditions. Different model systems induce distinctly different
pain attributes and thereby approximate processes that may or
may not be universally applicable to all clinical pain conditions.
The investigator needs to recognize that if it were not for the
directed inquiry into specific pain conditions treatment would
continue to be principally the same for all types of pain. Because
experimental models approximate, to various levels of degree,
the clinical phenomenon in question, the validity of the model
system and its limitations need to be well understood so that
acquired data can be interpreted relative to the disease in question.
In this respect, the validation process of the model itself constitutes
an important research effort.
In summary, experimental
models provide insight into complex processes and promote the
formulation of new research questions. The study of model pain
systems, even more than careful clinical descriptions, has led
to breakthrough discoveries and paradigm shifts in how researchers,
clinicians, and the public view particular diseases.
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