Formalin Injection Into Knee Joints of Rats: Pharmacologic Characterization of a Deep Somatic Nociceptive Model

Martins, M.A.; Bastos, Lúcia de Castro; Tonussi, Carlos Rogério

doi:10.1016/j.jpain.2005.09.002

Cited by 32 publications

(19 citation statements)

References 52 publications

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“…Opioids, as morphine, are able to inhibit both phases, and anti-inflammatory agents (aspirin, indomethacin and dexamethasone) only block the second phase (Hunskaar and Hole, 1987;Le Bars et al, 2001). In this assay, substance P and bradykinin are generated in the neurogenic phase, while other chemical mediators, such as histamine, serotonin and prostaglandin, are involved in the nociceptive response of the second stage (Martins et al, 2006). Considering our results, EEPR inhibited both phases, but rutin and quercetin were active only in the second stage.…”

Section: Ligandsmentioning

confidence: 60%

Pharmacological potential of Palicourea rigida kunth: A possible participation of flavonoid compounds

Moraes¹,

Santos²,

Fabri³

et al. 2017

J. Med. Plants Res.

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Palicourea rigida Kunth (Rubiaceae), also called "bate-caixa" or "douradão", has been used as antihypertensive, antiulcerogenic, anti-inflammatory and analgesic by traditional communities. Pharmacological potential of the ethanol extract from P. rigida (EEPR) and two quercetin derivatives were investigated. Using the high performance liquid chromatography (HPLC) assay, EEPR was analyzed. Phenolic contents (total phenolic and flavonoids) were quantified by spectrophotometric methods. 2,2-diphenyl-1-pycrilhydrazil (DPPH), iron reducing power and β-carotene/linoleic acid bleaching tests were applied to estimate the antoxidant capacity of EEPR. Nociception (acetic acidinduced writhing, formalin and hot plate) and inflammation (carrageenan-induced paw edema and pleurisy) assays were performed. Molecular docking was used to measure the interactions' profiles of ligands (rutin and quercetin) and cyclooxigenases (COX-1 and COX-2). HPLC analysis identified rutin and quercetin derivatives. Expressive levels of total phenolic and flavonoids and a promising antioxidant effect were measured. EEPR, rutin and quercetin reduced the abdominal contortions. EEPR was effective against both phases of formalin, while rutin and quercetin inhibited the second phase. The latency time on hot plate significantly increased after treatment with EEPR. Inflammatory parameters (paw edema, exudate volume and leukocyte infiltrate) were diminished by EEPR, rutin and quercetin. The molecular docking showed that rutin and quercetin are capable of complexing with COX-1 and COX-2 favorably through physical-chemical interactions. The results suggest that EEPR showed a relevant pharmacological potential, which may be related to action of rutin and quercetin derivatives.Key words: Palicourea rigida, rutin, quercetin, antioxidant, antinociception, inflammation. INTRODUCTIONIn the body, the imbalance between oxidant/antioxidant in favor of the oxidation promotes the oxidative stress that causes proteins, lipids and DNA damages, as well as induces a variety of cellular responses through the generation of reactive oxygen species (ROS) that may be originated from cellular metabolism or environmental sources (Nita and Grzybowski, 2016). ROS have become a concern among researchers because they have been associated with a significant number of diseases involving inflammatory and painful processes that affect humans and animals. In inflammation, for example, ROS cause vascular damage which allows the permeability of macromolecules and inflammatory cells from the blood to tissue (Mittal et al., 2014). This permeability is controlled by vasoactive and chemotactic mediators, which make the inflammatory process active, including the pain (Silva, 2015). Among the mediators that regulate the events of inflammation, vasoactive amines, lipid-derived eicosanoids, cytokines, chemokines and adhesion molecules have been highlighted (Silva, 2015). On the other hand, the inflammatory pain has been treated with non-steroidal anti-inflammatory agents, but present high prevalenc...

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Section: Ligandsmentioning

confidence: 60%

Pharmacological potential of Palicourea rigida kunth: A possible participation of flavonoid compounds

Moraes¹,

Santos²,

Fabri³

et al. 2017

J. Med. Plants Res.

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“…It was observed that 75% of answers have pointed to continuous ultrasound for pain relief, with just 17.1% using 50% pulse cycles, being that most doses were between 1 and 2W/cm 2 2 , in spite of hints indicating the usefulness of lower intensities for the treatment 1 , that is, there is the need for studies evaluating lower intensities and different ultrasound release ways. In our study, the irritation model has as major feature two nociceptive behavior stages separated by a quiescence stage around the fifth to the tenth minute after formalin injection 11 . So, we decided to carry out the first evaluation 15 minutes after injury, avoiding evaluating in the quiescent period, with new evaluation 30 and 60 minutes after, aiming at observing nociceptive and edema behavior along 1h after injury.…”

Section: Discussionmentioning

confidence: 94%

Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats

Bertolini¹,

Coradini²,

Kunz³

et al. 2014

Revista Dor

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BACKGROUND AND OBJECTIVES:Among electro agents ultrasound is one of the most common, however, there is insufficient evidence of the beneficial effects with the parameters currently used. The aim of this study was to compare the effect of continuous and pulsed ultrasound therapy on experimental hyperalgesia and edema in knees of Wistar rats. METHODS: 18 rats were divided into three groups: CG-control group; GUP -treated with pulsed ultrasound 50%; and GUC -continuous ultrasound. To accomplish the lesion, animals were manually restrained and 100µL of 5% formalin solution were injected into the right tibiofemoral space. For assessment of nociception digital Von Frey filament was used on the medial side of the joint, until clinching. Edema was evaluated with mid-lateral knee caliper. Assessments occurred in the preinjury (EV1), after 15 (EV2), 30 (EV3) and 60 (EV4) minutes of the injury. After EV2, treatment was initiated with ultrasound with 0.4W/cm 2 (SATA), pulsed or continuous. RESULTS:The CG had hypernociception, with no return to baseline. GUP has returned to baseline as from EV3 and for continuous ultrasound in EV4. All three groups showed similar behavior for edema, with onset in EV2, without reduction. CONCLUSION: Therapeutic ultrasound was effective to decrease nociception, and the pulsed form showed early results, however, both forms of application had no effect on the formation and maintenance of acute edema. Keywords: Edema, Pain measurement, Ultrasound therapy. Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats* RESUMO JUSTIFICATIVA E OBJETIVOS:Dentre os agentes eletrotér-micos o ultrassom é um dos mais comuns, contudo, há insuficiente evidência dos efeitos benéficos com os parâmetros correntemente utilizados. Assim, o objetivo deste estudo foi comparar o efeito do ultrassom terapêutico contínuo e pulsado sobre hiperalgesia e edema experimentais em joelhos de ratos Wistar. MÉTODOS: Foram utilizados 18 ratos, divididos em três grupos: GC -grupo controle; GUP -tratado com ultrassom pulsado 50%; e, GUC -ultrassom contínuo. Para realizar a lesão, os animais foram contidos manualmente e 100µL de solução de formalina a 5% foram injetados no espaço tíbio-femoral direito. Para avaliação da nocicepção foi utilizado o filamento de Von Frey digital, na face medial da articulação, até a retirada do membro. A avaliação do edema foi realizada com paquimetria médio-lateral ao joelho. As avaliações ocorreram no momento pré-lesão (AV1), após 15 (AV2), 30 (AV3) e 60 (AV4) minutos da lesão. Após AV2, foi iniciado o tratamento com ultrassom com 0,4W/ cm² (SATA), de forma pulsada ou contínua. RESULTADOS: Para GC, houve a presença de hipernocicepção, sem retorno aos valores basais. Para GUP houve retorno aos valores basais a partir de AV3 e para o ultrassom contínuo em AV4. Para o edema, os três grupos apresentaram comportamento semelhante, com formação em AV2, sem redução posterior. CONCLUSÃO: O ultrassom terapêutico mostrou-se eficaz para redução do quadro nociceptivo, sen...

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“…The animals were manually held and injected 100µl of 5% formalin solution in the tibiofemoral articular space for hyperalgesia induction 10 .…”

Section: Experimental Model Of Hyperalgesia Inductionmentioning

confidence: 99%

Uso do exercício resistido antagonizado por naloxone como fator de analgesia em sinovite aguda de joelho de ratos Wistar

Bertolini

Rosa

Silva

et al. 2012

Rev Bras Med Esporte

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Analgesia arising from exercising can occur via release of endogenous opioids in the central nervous system and periphery. However, the literature remains controversial about exercise ways and actions in pain. Thus, the aim of this study was to evaluate whether resistance exercise produces changes on the nociception and suffers interference by applying an opioid inhibitor. 18 rats divided into three groups were used: G1 -hyperalgesia on right knee and untreated; G2 -hyperalgesia and treated with jump sin water; G3-hyperalgesia with previous injection of naloxone and subsequent jumps. To produce hyperalgesia,100µl of 5% formalin was injected in the tibio femoral joint space. Pain was assessed using a digital von Frey filament on the right medial tibiofemoral joint. The evaluation periods were: pre-injury (EV1) after 15 minutes (EV2) and 30 minutes (EV3) and one hour (EV4). The applied exercise was jumpingin water and it occurred after EV2. The animal performed 4 sets of 5 jumps, with an interval of 3 minutes and overload of 50% of body weight. In G1, nociceptive increase was observed, with significant decrease and return to initial baseline values in AV4; G2 showed threshold restoration after exercise and return to baseline; G3 reduced thresholds, without restoration or significant increase in them. We concluded that there was analgesia withuse of exercise and that it was altered by blocking beta-endorphin.

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Formalin Injection Into Knee Joints of Rats: Pharmacologic Characterization of a Deep Somatic Nociceptive Model

Cited by 32 publications

References 52 publications

Pharmacological potential of Palicourea rigida kunth: A possible participation of flavonoid compounds

Pharmacological potential of Palicourea rigida kunth: A possible participation of flavonoid compounds

Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats

Uso do exercício resistido antagonizado por naloxone como fator de analgesia em sinovite aguda de joelho de ratos Wistar

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