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A new hybrid molecule incorporating both <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> and H<jats:sub>2<\/jats:sub>S donors into aspirin (<jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin inhibits acetic acid\u2010induced writhing response and carrageenan (Cg)\u2010induced inflammatory hyperalgesia in a dose\u2010dependent (5\u2013150\u00a0<jats:italic>\u03bc<\/jats:italic>mol\/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin's antinociceptive effect was also greater and longer compared to aspirin upon complete Freund's adjuvant (<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>)\u2010induced inflammatory hyperalgesia. Mechanistically, <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin, but not aspirin, was able to reduce the production\/release of interleukin\u20101 beta (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>) during Cg\u2010induced paw inflammation. Furthermore, <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin, but not aspirin, reduced prostaglandin E<jats:sub>2<\/jats:sub>\u2010induced hyperalgesia, which was prevented by treatment with a ATP\u2010sensitive potassium channel (<jats:styled-content style=\"fixed-case\">K<jats:sub>ATP<\/jats:sub><\/jats:styled-content>) blocker (glibenclamide; glib.). Noteworthy, the antinociceptive effect of <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin was not associated with motor impairment. The present results indicate that <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin seems to present greater potency than aspirin to reduce inflammatory pain in several models. The enhanced effects of <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin seems to be due to its ability to reduce the production of pronociceptive cytokines such as <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101 <jats:italic>\u03b2<\/jats:italic> and directly block hyperalgesia caused by a directly acting hyperalgesic mediator in a mechanism dependent on modulation of <jats:styled-content style=\"fixed-case\">K<jats:sub>ATP<\/jats:sub><\/jats:styled-content> channels. In conclusion, we would like to suggest that <jats:styled-content style=\"fixed-case\">NOSH<\/jats:styled-content>\u2010aspirin represents a prototype of a new class of analgesic drugs with more potent effects than the traditional <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>, aspirin.<\/jats:p>","DOI":"10.1002\/prp2.133","type":"journal-article","created":{"date-parts":[[2015,6,12]],"date-time":"2015-06-12T12:05:03Z","timestamp":1434110703000},"source":"Crossref","is-referenced-by-count":33,"title":["<scp>NOSH<\/scp>\u2010aspirin (<scp>NBS<\/scp>\u20101120), a dual nitric oxide and hydrogen sulfide\u2010releasing hybrid, reduces inflammatory pain"],"prefix":"10.1002","volume":"3","author":[{"given":"Miriam D.","family":"Fonseca","sequence":"first","affiliation":[{"name":"Department of Pharmacology Ribeirao Preto Medical School University of S\u00e3o Paulo Av. 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