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NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain.

Fonseca MD, Cunha FQ, Kashfi K, Cunha TM - Pharmacol Res Perspect (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil.

ABSTRACT
The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S 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 μmol/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-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) 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 KATP 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.

No MeSH data available.


Related in: MedlinePlus

Effect of NOSH-aspirin (NOSH-ASA) and aspirin on PGE2-induced hyperalgesia: involvement of KATP. (A) Mice were pretreated 50 min before with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle (v) orally followed by intraplantar (i.p.) injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. (B) Mice were pretreated with KATP blocker (glibenclamide; 10 mg/kg, i.p.) and after 30 min, they received vehicle or NOSH-ASA (150 μmol/kg), and after 50 min all groups received i.p. injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. Data are the means ± SEM (n = 6). **P < 0.01 and ***P < 0.001 versus vehicle group, #P < 0.001 versus NOSH-ASA-treated group. KATP, ATP-sensitive potassium channel; PGE2, prostaglandin E2.
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fig06: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on PGE2-induced hyperalgesia: involvement of KATP. (A) Mice were pretreated 50 min before with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle (v) orally followed by intraplantar (i.p.) injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. (B) Mice were pretreated with KATP blocker (glibenclamide; 10 mg/kg, i.p.) and after 30 min, they received vehicle or NOSH-ASA (150 μmol/kg), and after 50 min all groups received i.p. injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. Data are the means ± SEM (n = 6). **P < 0.01 and ***P < 0.001 versus vehicle group, #P < 0.001 versus NOSH-ASA-treated group. KATP, ATP-sensitive potassium channel; PGE2, prostaglandin E2.

Mentions: NO and H2S are able to reduced inflammatory hyperalgesia by acting directly on neuronal excitability through modulation of KATP channels (Soares et al. 2000; Cunha et al. 2008a). Therefore, in the next step we evaluated whether NOSH-aspirin was able to reduce hyperalgesia produced by a directly acting hyperalgesic mediator, PGE2, and whether this effect was dependent on KATP channels modulation. First, it was observed that pretreatment with NOSH-aspirin, but not with aspirin, was able to reduce PGE2-induced mechanical hyperalgesia (Fig.6A). Furthermore, the antinociceptive effect of NOSH-aspirin upon PGE2-induced hyperalgesia was prevented when mice were treated with a KATP channels blocker (glib.) (Fig.6B). As a control, glibenclaminde alone caused no change in PGE2-induced hyperalgesia (Fig.6B). Therefore, these results further indicate that the additive effects of NOSH-aspirin over aspirin might be partially due to its direct effect on inflammatory hyperalgesia through up modulation of KATP currents.


NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain.

Fonseca MD, Cunha FQ, Kashfi K, Cunha TM - Pharmacol Res Perspect (2015)

Effect of NOSH-aspirin (NOSH-ASA) and aspirin on PGE2-induced hyperalgesia: involvement of KATP. (A) Mice were pretreated 50 min before with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle (v) orally followed by intraplantar (i.p.) injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. (B) Mice were pretreated with KATP blocker (glibenclamide; 10 mg/kg, i.p.) and after 30 min, they received vehicle or NOSH-ASA (150 μmol/kg), and after 50 min all groups received i.p. injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. Data are the means ± SEM (n = 6). **P < 0.01 and ***P < 0.001 versus vehicle group, #P < 0.001 versus NOSH-ASA-treated group. KATP, ATP-sensitive potassium channel; PGE2, prostaglandin E2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492749&req=5

fig06: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on PGE2-induced hyperalgesia: involvement of KATP. (A) Mice were pretreated 50 min before with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle (v) orally followed by intraplantar (i.p.) injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. (B) Mice were pretreated with KATP blocker (glibenclamide; 10 mg/kg, i.p.) and after 30 min, they received vehicle or NOSH-ASA (150 μmol/kg), and after 50 min all groups received i.p. injection of PGE2. Mechanical hyperalgesia was evaluated 60 min after PGE2 injection. Data are the means ± SEM (n = 6). **P < 0.01 and ***P < 0.001 versus vehicle group, #P < 0.001 versus NOSH-ASA-treated group. KATP, ATP-sensitive potassium channel; PGE2, prostaglandin E2.
Mentions: NO and H2S are able to reduced inflammatory hyperalgesia by acting directly on neuronal excitability through modulation of KATP channels (Soares et al. 2000; Cunha et al. 2008a). Therefore, in the next step we evaluated whether NOSH-aspirin was able to reduce hyperalgesia produced by a directly acting hyperalgesic mediator, PGE2, and whether this effect was dependent on KATP channels modulation. First, it was observed that pretreatment with NOSH-aspirin, but not with aspirin, was able to reduce PGE2-induced mechanical hyperalgesia (Fig.6A). Furthermore, the antinociceptive effect of NOSH-aspirin upon PGE2-induced hyperalgesia was prevented when mice were treated with a KATP channels blocker (glib.) (Fig.6B). As a control, glibenclaminde alone caused no change in PGE2-induced hyperalgesia (Fig.6B). Therefore, these results further indicate that the additive effects of NOSH-aspirin over aspirin might be partially due to its direct effect on inflammatory hyperalgesia through up modulation of KATP currents.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil.

ABSTRACT
The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S 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 μmol/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-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) 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 KATP 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.

No MeSH data available.


Related in: MedlinePlus