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2014 ; 8
(2
): 143-51
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Descending pain modulation and chronification of pain
#MMPMID24752199
Ossipov MH
; Morimura K
; Porreca F
Curr Opin Support Palliat Care
2014[Jun]; 8
(2
): 143-51
PMID24752199
show ga
PURPOSE OF REVIEW: Chronic pain is an important public health problem that
negatively impacts quality of life of affected individuals and exacts an enormous
socio-economic cost. Currently available therapeutics provide inadequate
management of pain in many patients. Acute pain states generally resolve in most
patients. However, for reasons that are poorly understood, in some individuals,
acute pain can transform to a chronic state. Our understanding of the risk
factors that underlie the development of chronic pain is limited. Recent studies
have suggested an important contribution of dysfunction in descending pain
modulatory circuits to pain 'chronification'. Human studies provide insights into
possible endogenous and exogenous factors that may promote the conversion of pain
into a chronic condition. RECENT FINDINGS: Descending pain modulatory systems
have been studied and characterized in animal models. Human brain imaging
techniques, deep brain stimulation and the mechanisms of action of drugs that are
effective in the treatment of pain confirm the clinical relevance of top-down
pain modulatory circuits. Growing evidence supports the concept that chronic pain
is associated with a dysregulation in descending pain modulation. Disruption of
the balance of descending modulatory circuits to favour facilitation may promote
and maintain chronic pain. Recent findings suggest that diminished descending
inhibition is likely to be an important element in determining whether pain may
become chronic. This view is consistent with the clinical success of drugs that
enhance spinal noradrenergic activity, such as serotonin/norepinephrine reuptake
inhibitors (SNRIs), in the treatment of chronic pain states. Consistent with this
concept, a robust descending inhibitory system may be normally engaged to protect
against the development of chronic pain. Imaging studies show that higher
cortical and subcortical centres that govern emotional, motivational and
cognitive processes communicate directly with descending pain modulatory circuits
providing a mechanistic basis to explain how exogenous factors can influence the
expression of chronic pain in a susceptible individual. SUMMARY: Preclinical
studies coupled with clinical pharmacologic and neuroimaging investigations have
advanced our understanding of brain circuits that modulate pain. Descending pain
facilitatory and inhibitory circuits arising ultimately in the brainstem provide
mechanisms that can be engaged to promote or protect against pain
'chronification'. These systems interact with higher centres, thus providing a
means through which exogenous factors can influence the risk of pain
chronification. A greater understanding of the role of descending pain modulation
can lead to novel therapeutic directions aimed at normalizing aberrant processes
that can lead to chronic pain.
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