Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice

Diniz, Danuza Montijo; Souza, Alessandra Hübner de; Pereira, Elizete Maria Rita; Silva, Juliana Figueira da; Rigo, Flávia Karine; Romano‐Silva, Marco A.; Binda, Nancy Scardua; Castro, Célio José de; Cordeiro, Marta N.; Ferreira, Juliano; Gomez, Marcus V.

doi:10.1016/j.pbb.2014.09.017

Cited by 31 publications

(22 citation statements)

References 35 publications

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“…The capsaicin test represents an appropriate model of nociception because the application of capsaicin in humans and in experimental animals evokes intense acute pain (Diniz et al, 2014). Here, we demonstrated that Eta orally administered, as well as the positive control diclofenac sodium, reduced the capsaicin-induced nociception.…”

Section: Discussionmentioning

confidence: 60%

Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

Brum

Moreira

Silva

et al. 2016

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 60%

Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

Brum

Moreira

Silva

et al. 2016

Journal of Ethnopharmacology

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“…24 The most important transmission pathways for inflammatory pain are those comprising peripheral polymodal nociceptors sensitive to protons, such as acid sensitive ion channels and via endogenous mediators, such as bradykinin, serotonin, histamine, substance P, glutamate, ROS, cytokines and prostaglandins. 23,25,26 Moreover, it was demonstrated that the intraperitoneal administration of acetic acid induces the release not only of prostaglandins but also of mediators of the sympathetic nervous system. 27 Despite the poor specificity (e.g., tricyclic antidepressants, anticholinergic, antihistaminic and other agents showed activity in this test) of the writhing test, it is a very sensitive method for screening the antinociceptive effects of compounds.…”

Section: Acetic Acid-induced Writhingmentioning

confidence: 99%

Antinociceptive and Anti-inflammatory Activities of the Ethanolic Extract, of Fractions and of Epicatechin Isolated from the Stem Bark of Ximenia americana L. (Oleacaceae)

Uchôa¹,

Dias²,

Melo³

et al. 2018

Rev. Virtual Quim.

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Resumo:As ações antinociceptivas e anti-inflamatórias do extrato etanólico, das frações e da epicatequina (XM-Catequina) isolada a partir dos extratos etanólicos das cascas de Ximenia americana L. foram determinadas utilizando modelos in vivo como contorções induzidas pelo ácido acético, teste de formalina, teste de placa quente, peritonite induzida por zimosan e ensaio in vitro de inibição da ciclo-oxigenase. O teste de contorção revelou efeitos inibitórios maiores que 90% do extrato etanólico, das frações e da XM-Catequina (este isolado apresentou ID50 = ,0 μ ol / kg e efeito á i o = 99,60% . O teste de for ali a demonstrou um efeito antinociceptivo nas fases inicial (64.23%) e tardia (86.80%) com a XM-catequina, enquanto a fração clorofórmica mostrou menor efeito antinociceptivo na fase inicial (31.51%). A fração aquosa e o extrato etanólico causaram uma inibição significativa na fase tardia (73.68% e 82.40%, respectivamente). O tratamento de ratos com XM-catequina ou com a fração de acetato de etila não teve efeito antinociceptivo central no teste de placa quente. Os efeitos anti-inflamatórios foram determinados para a inflamação peritoneal induzida por zimosan e os dados indicaram que a XM-catequina, a fração hidrometanólica, o extrato etanólico e a fração em acetato de etila reduziram o número de células recrutadas em 46.02%, 35.06%, 41.45% e 38.61%, respectivamente. Estes resultados mostram que o extrato, as frações e a XM-catequina produzem respostas antinociceptivas e anti-inflamatórias. De acordo com os resultados obtidos nos ensaios de inibição da ciclooxigenase, os efeitos observados estão relacionados com a inibição de COX-1 e COX-2. As ações biológicas demonstradas no presente estudo apoiam o uso etnomedicinal desta planta.Palavras-chave: Plantas medicinais; anti-inflamatórios; corticosteroides; ciclooxigenase. AbstractThe antinociceptive and anti-inflammatory actions of the ethanolic extract, fractions and epicatechin (XM-Catechin) isolated from the ethanoic extracts of bark of Ximenia americana L. were determined utilizing in vivo models such as acetic acid-induced writhing, the formalin test, hot plate test, zymosan-induced peritonitis and in vitro cyclooxygenase inhibition assay. The writhing test revealed inhibitory effects higher than 90% of the ethanolic extract, fractions and XM-Catechin (this isolate presented ID50 = 32.03 µmol/kg and maximum effect = 99.60%). The formalin test demonstrated an antinociceptive effect in both early (64.23%) and late (86.80%) phases by XM-catechin, while the chloroform fraction showed a lower antinociceptive effect at the early phase (31.51%). The aqueous fraction and ethanolic extract caused significant inhibition at the late phase (73.68% and 82.40%, respectively). Treatment of mice with XM-catechin or with the ethyl acetate fraction had no central antinociceptive effect in the hot plate test. Anti-inflammatory effects were determined for zymosan-induced peritoneal inflammation and the data indicated that XM-catechin, the hydromethanol fraction, the ethanol...

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“…The release of pro-nociceptive neurotransmitters, such as glutamate, is tightly controlled by functional N-type channels in the spinal cord (Diniz et al, 2014;Souza et al, 2008). In agreement with this, our data showed that subarachnoid glutamate overspill, induced by formalin, was significantly reduced by PhTx3-4 preadministration.…”

Section: Discussionmentioning

confidence: 99%

“…Pha1b toxin is, to date, the most well characterized peptide with antinociceptive action from P. nigriventer venom. Previous studies in rodents have shown that this toxin has an antinociceptive potential in models of acute and persistent pain, including neuropathic, visceral, surgical, inflammatory and cancer pain models (Castro-Junior et al, 2013;de Souza et al, 2013;Diniz et al, 2014;Rigo et al, 2013aRigo et al, , 2013b. It is noteworthy, however, that Pha1b has a wider therapeutic window compared to u-conotoxin MVIIA and longer-lasting effects compared, for example, to morphine (de Souza et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the antinociceptive effect of PhTx3-4, a toxin from Phoneutria nigriventer , in models of thermal, chemical and incisional pain in mice

Silva

Castro

Oliveira

et al. 2015

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Venom-derived peptides constitute a unique source of drug prototypes for the pain management. Many of them can modulate voltage-gated calcium channels that are central in the processing of pain sensation. PhTx3-4 is a peptide isolated from Phoneutria nigriventer venom, which blocks high voltage-activated calcium channels with low specificity, thereby leading to neuroprotection in models of ischemia in vitro. The aim of the present work was evaluating the potential of intrathecal PhTx3-4 in the reversal of different nociceptive states in mice, furthermore assessing the potential of PhTx3-4 in triggering motor side effects. We found that bellow 100 pmol/site, PhTx3-4 did not cause major motor side effects. By comparison, ω-conotoxin MVIIA and ω-conotoxin MVIIC triggered motor side effects at the doses of 10 and 100 pmol/site, respectively. Also, PhTx3-4 (30 pmol/site) caused no significant alterations in the forced locomotor activity test (rotarod) and in the exploratory activity test (versamax). In a model of inflammatory persistent pain (formalin test), PhTx3-4 reversed nociceptive behavior both pre or post-administered, although this effect was observed only at the inflammatory phase of the test and not at the neurogenic phase. Comparatively, ω-conotoxin MVIIC was effective only when post-administered in the formalin test. Nonetheless, PhTx3-4 treatment was devoid of action in acute nociceptive thermal model (hotplate test), whereas morphine showed efficacy in this test. Efficacy of PhTx3-4 in the formalin test was associated with inhibition of formalin-induced glutamate release in the cerebrospinal fluid. PhTx3-4, but not ω-conotoxin MVIIC, reversed NMDA-induced nociceptive behavior indicating a putative role of PhTx3-4 at ionotropic glutamate receptors. Finally, we observed efficacy of PhTx3-4 in ameliorating mechanical hypersensitivity induced by paw incision, a post-operative and more clinically relevant pain model. Taken together, our data show that PhTx3-4 possesses antinociceptive effect in different models of pain in mice, suggesting that this toxin may serve as drug prototype for pain control.

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Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice

Cited by 31 publications

References 35 publications

Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

Antinociceptive and Anti-inflammatory Activities of the Ethanolic Extract, of Fractions and of Epicatechin Isolated from the Stem Bark of Ximenia americana L. (Oleacaceae)

Characterization of the antinociceptive effect of PhTx3-4, a toxin from Phoneutria nigriventer , in models of thermal, chemical and incisional pain in mice

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