title: Skin vasodilation and analgesic effect of a topical nitric oxide-releasing hydrogel.
abstract: 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.
authors.affiliation: Institute of Chemistry, University of Campinas-UNICAMP, CP 6154, Campinas, SP 13087-970, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vercelino
authors.forename: Thiago Mattar
authors.initials: TM
authors.lastname: Cunha
authors.forename: Elisa Silva
authors.initials: ES
authors.lastname: Ferreira
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Sérgio H
authors.initials: SH
authors.lastname: Ferreira
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: de Oliveira
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020100:Hydrogels; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000700:Analgesics; D020100:Hydrogels; D014665:Vasodilator Agents; D009569:Nitric Oxide