Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization

Tonussi, Carlos Rogério; Ferreira, S. H.

doi:10.1016/0014-2999(94)90398-0

Cited by 156 publications

(71 citation statements)

References 28 publications

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“…NSAIDs decrease pain caused by inflammation (Tonussi and Ferreira, 1994), and a low pH environment around sites of inflammation has been proposed as a major contributing factor of inflammatory pain. In addition, more direct evidence that NSAIDs specifically inhibit acid pain has previously been demonstrated by Steen et al (1995a).…”

Section: Effect Of Inhibitors Of Asics: Nsaidsmentioning

confidence: 99%

Acid-Induced Pain and Its Modulation in Humans

Jones¹,

Slater²,

Cadiou³

et al. 2004

J. Neurosci.

219

166

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Despite the discovery of ion channels that are activated by protons, we still know relatively little about the signaling of acid pain. We used a novel technique, iontophoresis of protons, to investigate acid-induced pain in human volunteers. We found that transdermal iontophoresis of protons consistently caused moderate pain that was dose-dependent. A marked desensitization occurred with persistent stimulation, with a time constant of ϳ3 min. Recovery from desensitization occurred slowly, over many hours. Acid-induced pain was significantly augmented in skin sensitized by acute topical application of capsaicin. However, skin desensitized by repeated capsaicin application showed no significant reduction in acid-induced pain, suggesting that both capsaicin-sensitive and insensitive sensory neurons contribute to acid pain. Furthermore, topical application of non-steroidal anti-inflammatory drugs (NSAIDs) significantly attenuated acid-evoked pain but did not affect the heat pain threshold, suggesting a specific interaction between NSAIDs and peripheral acid sensors. Subcutaneous injection of amiloride (1 mM) also significantly inhibited the pain induced by iontophoresis of acid, suggesting an involvement of acid-sensing ion channel (ASIC) receptors. Conversely, iontophoresis of acid over a wide range of skin temperatures from 4 to 40°C produced only minor changes in the induced pain. Together these data suggest a prominent role for ASIC channels and only a minor role for transient receptor potential vanilloid receptor-1 as mediators of cutaneous acid-induced pain.

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Section: Effect Of Inhibitors Of Asics: Nsaidsmentioning

confidence: 99%

Acid-Induced Pain and Its Modulation in Humans

Jones¹,

Slater²,

Cadiou³

et al. 2004

J. Neurosci.

219

166

View full text Add to dashboard Cite

show abstract

“…Moreover, the antinociception achieved with these drugs was mimicked by NO donors such as sodium nitroprusside. The involvement of this pathway has also been demonstrated for other analgesics, such as dipyrone (Duarte et al, 1992), diclofenac (Tonussi et al, 1994), and some antinociceptive agents, such as Crotalus durissus terrificus snake-venom (Picolo et al, 2000), the potent κ-opioid receptor agonist bremazocine (Amarante & Duarte, 2002), xylazine (Romero & Duarte, 2009), the cannabinoid receptor agonist anandamida (Reis et al, 2009) and ketamine (Romero et al, 2011). In agreement with in vivo studies, data from electrophysiological experiments studying inflammatory sensitisation showed that capsaicin-induced elevations in intracellular Ca 2+ levels of rat sensory neurons lead to an enhanced production of cGMP via the NO pathway.…”

Section: Pkg Signalling and Pain Controlmentioning

confidence: 83%

Protein Kinases and Pain

Funez¹,

Souza²,

Pandossio³

et al. 2012

Protein Kinases

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“…Esse mecanismo poderia ser explicado pelo aumento da concentração de endorfinas no plasma 16 . Tonussi e Ferreira 17 consideram que a principal ação analgésica do diclofenaco não está associada à prevenção da sensibilização dos receptores dolorosos, mas é secundária a uma dessensibilização desses receptores, já sensibilizados. Essa auto-regulação funcional seria o resultado da estimulação periférica do cGMP, através da ativação da via arginina-óxido nítrico, mecanismo proposto pelo mesmo grupo para a atuação de outros analgésicos, dentre os quais a dipirona 18 .…”

Section: Migrânea Sem Auraunclassified

Diclofenaco intramuscular no tratamento agudo da migrânea: um estudo duplo cego placebo controlado

Bigal

Bordini

Speciali

2002

Arq. Neuro-Psiquiatr.

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O objetivo do presente estudo é avaliar, com mascaramento duplo, o efeito do diclofenaco sobre a dor e sintomas associados em pacientes com crise de migrânea. Sessenta pacientes com migrânea com aura e sessenta pacientes com migrânea sem aura foram randomizados para receber diclofenaco intramuscular, na dose de 75 mg, associado com injeção intravenosa de solução salina, 10 ml, ou para receber solução salina isoladamente. Três parâmetros de avaliação analgésica e uma escala analógica para avaliar os sintomas associados foram usados. Aferimos ainda os percentuais de recorrência e de utilização de medicação de resgate. Pacientes que receberam diclofenaco apresentaram redução na intensidade da dor estatisticamente significativa, 60 minutos após a administração, em dois dos três parâmetros utilizados (migrânea sem aura) e nos três parâmetros utilizados (migrânea com aura). Não observamos diferença, comparado com o placebo, na intensidade dos sintomas associados. Houve redução da recorrência e da utilização de medicação de resgate. A despeito de ser uma opção no tratamento das migrâneas em unidades de emergência, o diclofenaco apresenta início de ação lento e nenhum efeito nos sintomas associados.

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Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization

Cited by 156 publications

References 28 publications

Acid-Induced Pain and Its Modulation in Humans

Acid-Induced Pain and Its Modulation in Humans

Protein Kinases and Pain

Diclofenaco intramuscular no tratamento agudo da migrânea: um estudo duplo cego placebo controlado

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