Synergistic interaction between meloxicam and aminoguanidine in formalin‐induced nociception in mice

Dudhgaonkar, Shailesh; Tandan, Surendra K.; Kumar, Dinesh; Arunadevi, R.; Prakash, Vellanki Ravi

doi:10.1016/j.ejpain.2007.06.006

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…Systemic administration of meloxicam produced a dose-related antinociceptive effect during the second phase of the assay. Our results agree with previous studies showing that systemic meloxicam is able to reduce nociception in several pain animal models [Engelhardt et al, 1995;Laird et al, 1997;Santos et al, 1998;Pinardi et al, 2003;Dudhgaonkar et al, 2008]. The findings of the study also confirm that opioids and nonsteroidal antiinflammatory drugs (NSAIDs) show different profiles of antinociceptive activity, as tramadol exhibited greater antinociceptive potency and efficacy ( Fig.…”

Section: Mechanism Of Actionsupporting

confidence: 92%

Synergism between tramadol and meloxicam in the formalin test involves both opioidergic and serotonergic pathways

Isiordia-Espinoza¹,

Terán-Rosales²,

Reyes-Garcı́a³

et al. 2011

Drug Development Research

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This study was designed to evaluate the antinociceptive interaction of the tramadol-meloxicam combination in different proportions (tramadol 1 meloxicam in 1:1, 1:3, and 3:1 ratios), as well as the role of nitric oxide, opioidergic, and serotonergic pathways in the antinociceptive effect of the combination. The effects of individual drugs and fixed-ratio combinations were assayed using the 3% formalin test in mice. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Tramadol (3.16-10 mg/kg, i.m.), meloxicam (3.16-17.8 mg/kg, i.m.), and tramadolmeloxicam combinations produced a dose-dependent antinociceptive effect. ED 30 values were estimated for the individual drugs, and isobolograms were constructed. The tramadol 1 meloxicam 1:1 and 1:3 ratio combinations showed synergistic interactions while the 3:1 ratio produced additive effects. Naloxone (1 mg/kg, i.m.) or methiothepin (0.1 mg/kg, i.m.), but not L-NAME (3 mg/kg, i.m.), prevented the antinociceptive effects of the combination. These data suggest that (1) the tramadol-meloxicam combination produces a functional synergistic interaction that involves both opioid and serotonin receptors, and (2) this combination may be a promising tool in pain management. Drug Dev Res, 2011.

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Section: Mechanism Of Actionsupporting

confidence: 92%

Synergism between tramadol and meloxicam in the formalin test involves both opioidergic and serotonergic pathways

Isiordia-Espinoza¹,

Terán-Rosales²,

Reyes-Garcı́a³

et al. 2011

Drug Development Research

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show abstract

“…Thus, the reduced peripheral nociceptive input and the prevented central spinal sensitization could be working together, resulting in antinociception. Synergic interactions have been observed between other different drugs and systems (32,33). Cannabinoid antinociceptive synergy between topical and spinal sites has already been reported, showing that peripheral-spinal integration is not unlikely to occur (34).…”

Section: Discussionmentioning

confidence: 94%

Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway

Nascimento

Branco

2009

Braz J Med Biol Res

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We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclasecGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 μL of a 1% formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80% in the first and 25% in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40% reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.

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“…NO is synthesized from l-arginine by three structurally distinct isoforms of the NOS family: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) (Boettger et al, 2007;Salerno et al, 2002). Among the three NOS isoforms, iNOS plays an important role in pain conditions with an inflammatory component (Dudhgaonkar et al, 2008;LaBuda et al, 2006). Of the three extracts, only CE showed a significant decrease (p < 0.001) in NO production in LPSactivated J744A.1 in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 96%

Involvement of the l-arginine-nitric oxide pathway in the antinociception caused by fruits of Prosopis strombulifera (Lam.) Benth.

Saragusti

Bustos

Pierosan

et al. 2012

Journal of Ethnopharmacology

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Synergistic interaction between meloxicam and aminoguanidine in formalin‐induced nociception in mice

Abstract: Co-administration of meloxicam and aminoguanidine showed synergistic antinociceptive effect which might possibly reduce gastrointestinal toxicity associated with the use of meloxicam.

Cited by 14 publications

References 63 publications

Synergism between tramadol and meloxicam in the formalin test involves both opioidergic and serotonergic pathways

Synergism between tramadol and meloxicam in the formalin test involves both opioidergic and serotonergic pathways

Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway

Involvement of the l-arginine-nitric oxide pathway in the antinociception caused by fruits of Prosopis strombulifera (Lam.) Benth.

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