Treatment of complex regional pain syndrome type I with oral phenoxybenzamine: rationale and case reports

The nonselective alpha-adrenergic antagonist, phenoxybenzamine, has been used in the treatment of neuropathic pain syndromes, specifically, complex regional pain syndrome (CRPS) types I and II. This agent has also previously been used in intravenous regional peripheral blocks for treatment of CRPS I; however, an intravenous preparation of phenoxybenzamine is not currently available in the U.S.A. In this case series, systemic administration was more appropriate for three of the four patients, as their syndromes had spread beyond the initial area of surgery or trauma. We report an apparent clinical benefit in three of the four patients following oral administration. We postulate that this may be due to the noncompetitive (irreversible) blockade of alpha(1)- and alpha(2)-adrenergic receptors. We further hypothesize that this blockade could reduce stimulation of an increased population of adrenergic receptors in hyperalgesic skin, blunt the stimulation by norepinephrine of alpha(2)-adrenergic receptors on macrophages, and ultimately reduce the release of proinflammatory cytokines from cellular elements.