Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

Abstract

The present results support the hypothesis that allodynia in an animal model of CRPS is effectively relieved by topical combinations of α2A receptor agonists or NO donors with PA or PDE inhibitors. This suggests that topical treatments aimed at improving microvascular function by increasing both arterial and capillary blood flow produce effective analgesia for CRPS.

Capillary dysfunction and impaired tissue oxygenation in complex regional pain syndrome: A hypothesis

“…We speculate that the recent failure of tadalafil to elevate limb temperature [37] is the result of capillary dysfunction, which causes a dissociation between tissue oxygenation on one hand, and limb blood flow/ temperature on the other. Studies in a post-ischemic pain model confirm that systemic PDE [46], as well as topical PDE application either alone or in combination with vasodilators [37], relieve allodynia while reversing the suppression of flow responses [31], consistent with a role of elevated CTH and tissue hypoxia in this model.…”

Anti-allodynic Effect of Mangiferin in Rats With Chronic Post-ischemia Pain: A Model of Complex Regional Pain Syndrome Type I

“…Additonally, it was previously reported that MG inhibited ET-1 secretion and restored the loss of NO production when cells were exposed to high glucose under endoplasmic reticulum stress conditions ( Song et al, 2015 ). An earlier study of the CPIP model revealed that topical combinations including α 2A receptor agonists, phosphodiesterase four inhibitors, or NO donors improved both arterial and capillary blood flow associated with effective analgesia ( Ragavendran et al, 2013 ; Laferrière et al, 2014 ). All these facts add support to our interpretation that MG relaxant properties may be closely related to the activation of the NO-cGMP pathway in CPIP.…”

Comment on “In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain” by Vasudeva et al., J. Neuroimmunol. 2015 June; 283:3–49

“…Pentoxifylline is a drug with multiple mechanisms of action that has been typically used in vascular claudication to improve microcirculatory blood flow and thus reduce the symptoms of tissue ischemia (Laferriere et al, 2014). In more recent times, pentoxifylline has demonstrated widespread neuroinflammatory effects of a potentially beneficial nature in pain models (Liu et al, 2007).…”