Open AccessNOSH ‐aspirin ( NBS ‐1120), a dual nitric oxide and hydrogen sulfide‐releasing hybrid, reduces inflammatory pain
Author(s) -
Fonseca Miriam D.,
Cunha Fernando Q.,
Kashfi Khosrow,
Cunha Thiago M.
Publication year - 2015
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.133
Subject(s) - aspirin , pharmacology , hyperalgesia , chemistry , nitric oxide , nociception , medicine , biochemistry , receptor , organic chemistry
The development of nitric oxide ( NO )‐ and hydrogen sulfide (H 2 S)‐releasing nonsteroidal anti‐inflammatory drugs ( NSAID s) has generated more potent anti‐inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H 2 S donors into aspirin ( NOSH ‐aspirin) 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 NOSH ‐aspirin inhibits acetic acid‐induced writhing response and carrageenan (Cg)‐induced inflammatory hyperalgesia in a dose‐dependent (5–150 μ mol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH ‐aspirin's antinociceptive effect was also greater and longer compared to aspirin upon complete Freund's adjuvant ( CFA )‐induced inflammatory hyperalgesia. Mechanistically, NOSH ‐aspirin, but not aspirin, was able to reduce the production/release of interleukin‐1 beta ( IL ‐1 β ) during Cg‐induced paw inflammation. Furthermore, NOSH ‐aspirin, but not aspirin, reduced prostaglandin E 2 ‐induced hyperalgesia, which was prevented by treatment with a ATP‐sensitive potassium channel ( K ATP ) blocker (glibenclamide; glib.). Noteworthy, the antinociceptive effect of NOSH ‐aspirin was not associated with motor impairment. The present results indicate that NOSH ‐aspirin seems to present greater potency than aspirin to reduce inflammatory pain in several models. The enhanced effects of NOSH ‐aspirin seems to be due to its ability to reduce the production of pronociceptive cytokines such as IL ‐1 β and directly block hyperalgesia caused by a directly acting hyperalgesic mediator in a mechanism dependent on modulation of K ATP channels. In conclusion, we would like to suggest that NOSH ‐aspirin represents a prototype of a new class of analgesic drugs with more potent effects than the traditional NSAID , aspirin.