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2010 ; 11
(8
): 1224-38
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A hypothesis for the cause of complex regional pain syndrome-type I (reflex
sympathetic dystrophy): pain due to deep-tissue microvascular pathology
#MMPMID20704671
Coderre TJ
; Bennett GJ
Pain Med
2010[Aug]; 11
(8
): 1224-38
PMID20704671
show ga
Complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) is a
chronic pain condition that usually follows a deep-tissue injury such as fracture
or sprain. The cause of the pain is unknown. We have developed an animal model
(chronic post-ischemia pain) that creates CRPS-I-like symptomatology. The model
is produced by occluding the blood flow to one hind paw for 3 hours under general
anesthesia. Following reperfusion, the treated hind paw exhibits an initial phase
of hyperemia and edema. This is followed by mechano-hyperalgesia,
mechano-allodynia, and cold-allodynia that lasted for at least 1 month. Light
microscopic analyses and electron microscopic analyses of the nerves at the site
of the tourniquet show that the majority of these animals have no sign of injury
to myelinated or unmyelinated axons. However, electron microscopy shows that the
ischemia-reperfusion injury produces a microvascular injury, slow-flow/no-reflow,
in the capillaries of the hind paw muscle and digital nerves. We propose that the
slow-flow/no-reflow phenomenon initiates and maintains deep-tissue ischemia and
inflammation, leading to the activation of muscle nociceptors, and the ectopic
activation of sensory afferent axons due to endoneurial ischemia and
inflammation. These data, and a large body of clinical evidence, suggest that in
at least a subset of CRPS-I patients, the fundamental cause of the abnormal pain
sensations is ischemia and inflammation due to microvascular pathology in deep
tissues, leading to a combination of inflammatory and neuropathic pain processes.
Moreover, we suggest a unifying idea that relates the pathogenesis of CRPS-I to
that of CRPS-II. Lastly, our hypothesis suggests that the role of the sympathetic
nervous system in CRPS-I is a factor that is not fundamentally causative, but may
have an important contributory role in early-stage disease.