2013
DOI: 10.1016/j.jpain.2012.10.004
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Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

Abstract: Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α 2 -adrenergic (α 2A ) receptor agonists or nitric oxide (NO) donors combined with eithe… Show more

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Cited by 17 publications
(29 citation statements)
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“…STZinduced hyperglycaemia leads to a pronounced neuropathic pain phenotype in the rat [20], and high levels of blood glucose lead to the development of mechanical and cold allodynia, and heat hyperalgesia. Heightened pain responses may arise as a result of damage to the peripheral nervous system from direct actions of glucose [5], metabolite production [9], inflammation [33], or microvascular damage and other associated micro-environmental changes [34]. The observed increase in small myelinated fibre profiles in sciatic nerve trunk may represent large fibre neuropathy, with demyelination of larger fibres [25], and hence smaller apparent cross sectional area both in the nerve fibre and somata.…”
Section: Discussionmentioning
confidence: 99%
“…STZinduced hyperglycaemia leads to a pronounced neuropathic pain phenotype in the rat [20], and high levels of blood glucose lead to the development of mechanical and cold allodynia, and heat hyperalgesia. Heightened pain responses may arise as a result of damage to the peripheral nervous system from direct actions of glucose [5], metabolite production [9], inflammation [33], or microvascular damage and other associated micro-environmental changes [34]. The observed increase in small myelinated fibre profiles in sciatic nerve trunk may represent large fibre neuropathy, with demyelination of larger fibres [25], and hence smaller apparent cross sectional area both in the nerve fibre and somata.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
Section: Discussionmentioning
confidence: 99%
“…The mechanisms by which ischemia might create pain have been reviewed by Coderre et al [7,37]. Briefly, tissue hypoxia would be expected to result in elevated lactate levels and acidosis secondary to energy depletion, as observed in the muscle and skin of CRPS patients [4,17,27].…”
Section: Origin Of Pain In Crpsmentioning
confidence: 99%
“…In CPIP rats, topical meldonium and combined meldonium‐NAC treatment produced a robust increase in PWT that was sustained for 2 hr. The agents relieved allodynia with comparable efficacy to vasoactive topical formulations previously investigated and reported by our group (Ragavendran et al, ). Unique to topical meldonium‐NAC is its tendency to produce significant elevation of PWT in the later stage of the CPIP disease spectrum‐ at 8 weeks post‐ischemia reperfusion injury.…”
Section: Discussionmentioning
confidence: 99%