Skin vasodilation and analgesic effect of a topical nitric oxide-releasing hydrogel
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New approaches based on topical treatments are needed for treating pain and impaired dermal blood flow. We used a topical Pluronic F127 hydrogel containing S-nitrosoglutathione (GSNO) as a prodrug to generate free NO, an effector molecule that exerts both dermal vasodilation and antinociceptive effects. GSNO-containing hydrogels underwent gelation above 12 °C and released free NO at rates that were directly dependent on the GSNO concentration in the range of 50–150 mM. The topical application of this material led to dose–response dermal vasodilation in healthy volunteers and to a reduction of up to 50 % of the hypernociception intensity in Wistar rats that were subjected to inflammatory pain. Mechanistic investigations indicated that the antinociceptive effect of the topical F127/GSNO hydrogels is produced by the local activation of the cGMP/PKG/KATP channel-signaling pathway, which was stimulated by the free NO that diffused through the skin. These results expand the scope of the biomedical applications of this material and may represent a new approach for the topical treatment of inflammatory pain.
KeywordsNitric Oxide Stratum Corneum KATP Channel Antinociceptive Effect GSNO
R.V. was supported by a Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP, postdoctoral fellowship (#2009/09800-4). E.S.F. received a FAPESP research trainee studentship (#2009/17235-5). This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq (#309390/2011-7 and #482646/2010-1). We thank Dr. Ieda Regina Schivo for technical assistance with animal husbandry and laboratory protocols, Mr. Natan V. de Castro for technical assistance with the HSDSC measurements and Mr. Iveraldo Rodrigues for technical assistance with the figures.
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