There is a relatively long history of the use of the α -
adrenergic antagonist,
phenoxybenzamine, for the treatment of
complex regional pain syndrome (CRPS). One form of this syndrome, CRPS I, was originally termed
reflex sympathetic dystrophy (RSD) because of an apparent dysregulation of the sympathetic nervous system in the region of an extremity that had been subjected to an injury or
surgical procedure. The syndrome develops in the absence of any apparent continuation of the inciting
trauma. Hallmarks of the condition are
allodynia (
pain perceived from a nonpainful stimulus) and
hyperalgesia (exaggerated
pain response to a painful stimulus). In addition to severe, unremitting
burning pain, the affected limb is typically warm and edematous in the early weeks after
trauma but then progresses to a primarily cold, dry limb in later weeks and months. The later stages are frequently characterized by changes to skin texture and nail
deformities,
hypertrichosis,
muscle atrophy, and bone demineralization. Earlier treatments of CRPS syndromes were primarily focused on blocking sympathetic outflow to an affected extremity. The use of an α -
adrenergic antagonist such as
phenoxybenzamine followed from this perspective. However, the current consensus on the etiology of CRPS favors an interpretation of the symptomatology as an evidence of decreased sympathetic activity to the injured limb and a resulting upregulation of
adrenergic sensitivity. The clinical use of
phenoxybenzamine for the treatment of CRPS is reviewed, and mechanisms of action that include potential immunomodulatory/anti-inflammatory effects are presented. Also, a recent study identified
phenoxybenzamine as a potential intervention for
pain mediation from its effects on gene expression in human cell lines; on this basis, it was tested and found to be capable of reducing
pain behavior in a classical animal model of
chronic pain.