Skin vasodilation and analgesic effect of a topical nitric oxide-releasing hydrogel

Author(s)

Vercelino, Rafael ^[1] ; Cunha, Thiago Mattar ^[2] ; Ferreira, Elisa Silva ^[1] ; Cunha, Fernando Q. ^[2] ; Ferreira, Sergio H. ^[2] ; de Oliveira, Marcelo G. ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Chem, BR-13087970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Fac Med, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE; v. 24, n. 9, p. 2157-2169, SEP 2013.
• Web of Science Citations: 20

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 A degrees 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. (AU)

• FAPESP's process: 09/09800-4 - EFFECT OF NITRIC OXIDE DONORS IN INFLAMMATORY HYPERNOCICEPTION
• Grantee: Rafael Vercelino
• Support Opportunities: Scholarships in Brazil - Post-Doctoral