Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms

Nunes, Rodolfo de Melo; Martins, Morgana Ramos; Silva, Francisco Saraiva da; Leite, Ana Caroline Rocha de Melo; Girão-Carmona, Virgínia Cláudia Carneiro; Cunha, Fernando; Marinho, Aryana Lushese Lima Feitosa; Pinto, Ana Carolina Matias Dinelly; Rocha, Francisco Airton Castro da

doi:10.1007/s00011-015-0860-7

Cited by 18 publications

(15 citation statements)

References 26 publications

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“…There was no improvement in pain behavior in the animals studied, with no impact on articular mobility, motor activity, or mechanical hyperalgesia in comparison to the control group. This finding could be related to the doses used in this experimental model, which were smaller than those used in other studies on this drug, varying from 300 to 625 mg/kg ( 27 , 31 ). That could probably be a limitation of our study, including the time period of medication usage.…”

Section: Discussionmentioning

confidence: 68%

“…This outcome differs from the findings of another study in which OA was induced in rats by zymosan. In that case, the animals were treated with higher doses of SrRan than in our study, ranging from 30 to 300 mg/kg –1 ·day –1 for a shorter period of time ( 27 ). The difference could be probably attributed to the different model applied, with higher doses used in that study.…”

Section: Discussionmentioning

confidence: 84%

“…That could probably be a limitation of our study, including the time period of medication usage. Experimental improvements were obtained with higher doses ( 27 , 31 ) and for longer periods ( 15 , 31 ). This experimental model determined that additional studies examining the use of SrRan in the treatment of OA are required, particularly investigations using higher doses of this drug.…”

Section: Discussionmentioning

confidence: 97%

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Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis

Rodrigues

Sampaio

Nunes

et al. 2017

Braz J Med Biol Res

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Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects of decreasing the risk of fractures and an indication of reducing the progression of osteoarthritis (OA). This study aimed to investigate the effects of SrRan as either a prophylactic or a treatment drug, using an OA rat model to assess pain behavior. A monoiodoacetate (MIA)-induced knee joint OA model in Wistar rats was used. Thirty Wistar rats (both sexes, 60 days old) were distributed in five groups of 6 rats each: the control group, that received no intervention; a prophylactic group, that received oral administration of 25 mg·kg-1·day-1 of SrRan for 28 days before induction of OA; a group treated with 25 mg·kg-1·day-1 of SrRan for 28 days after OA induction; a group treated with 50 mg·kg-1·day-1 during 28 days after OA induction; and a group that received oral saline for 28 days after induction. The assessment of pain behavior was performed considering articular incapacitation (weight-bearing test), mechanical hyperalgesia (Randall Selitto test) and motor activity (rotarod test), on days 0, 7, 14, 21, and 28. This experiment did not yield a significant difference when comparing the group that received SrRan prophylactically with the groups treated with 25 or 50 mg·kg-1·day-1 and the group that received oral saline. Thus, SrRan did not provide analgesia in either treated rats or as a prophylactic drug with the tested doses. Higher doses should be tested further to achieve possible significant results.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 97%

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Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis

Rodrigues

Sampaio

Nunes

et al. 2017

Braz J Med Biol Res

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“…Sr на разных моделях артрита у животных вызывает угнетение внутрисуставной продукции провоспалительных цитокинов [7]. Экзогенное введение в организм больных ОА Sr вызывает улучшение метаболических процессов в хряще и субхондральной кости, усиливает функцию остеобластов и угнетает дифференцировку остеокластов, стимулирует образование кости через пролиферацию преостеобластов, подавляет активность матриксных протеиназ в синовиальной среде суставов [23,24].…”

Section: Discussionunclassified

Клініко-Патогенетична Значущість Остеоасоційованих Мікроелементів При Хворобах Суглобів. Повідомлення ІІ. Мікроелементоз У Волоссі

Syniachenko¹,

Heiko²,

Сокрут³

et al. 2021

PJS

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Практична медицина / Practical Medicine Резюме. Актуальность работы. Микроэлементоз (дисбаланс в организме уровней отдельных микроэлементов-МЭ) рассматривается как одно из важных клинико-патогенетических составляющих дегенеративно-воспалительных болезней суставов, а МЭ могут играть роль кофакторов, участвующих в процессах артикулярного воспаления. Цель работы: изучить уровни в волосах и провести оценку клинико-патогенетической значимости остеоассоциированных МЭ (кобальта-Со, меди-Cu, железа-Fe, лития-Li, марганца-Mn, свинца-Pb, стронция-Sr, цинка-Zn) при различных артритахревматоидном (РА), реактивном урогенитальном хламидийиндуцированном (РеА), псориатическом (ПсА), подагрическом (ПА) и остеоартрите (ОА).

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“…In line with the current trend of investigating drugs that can control the inflammatory component of OA, pre-clinical studies with SrRan have been performed to test its possible effect in this setting. However, results showing the probable antinociceptive effects of SrRan have conflicted with those of alterations in levels of inflammatory mediators such as TNF-α and IL1-β ( Nunes et al, 2015 ; Alves et al, 2017 ; Mierzwa et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

et al. 2018

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Introduction: Strontium ranelate (SrRan) has the potential to interfere in the progression of osteoarthritis (OA), multifactorial disease associated with mechanical problems and articular inflammatory changes.Objectives: This study aimed to test the effects of prophylactic and therapeutic use of SrRan on clinical parameters of pain, the inflammatory process, and degradation of the articular cartilage.Methods: This was an experimental study, using a model of knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar rats were divided into five groups and treated as indicated: control, without intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for 28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day for 28 days after the induction; and model control, received saline solution after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia, tactile sensitivity, and forced ambulation), histological evaluation of articular cartilage, and determination of inflammatory cytokines in the synovial fluid (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α, and interferon [INF]-γ) were performed.Results: Both prophylactic and therapeutic treatments improved the articular discomfort. A prophylactic dose of 500 mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10, TNF-α, and IFN-γ in SrRan-treated groups with OA were not significantly different compared with those in the normal control animals. The histopathological evaluation showed less articular damage in the SrRan-treated and control groups compared to the saline-treated group.Conclusion: The prophylactic and therapeutic administration of SrRan was associated with improved behavioral patterns of pain, especially joint discomfort. SrRan administration mitigated histological changes in the articular cartilage and reduced the inflammatory process, which beneficially reduced the progression of OA in the experimental model studied.

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Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms

Abstract: SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

Cited by 18 publications

References 26 publications

Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis

Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis

Клініко-Патогенетична Значущість Остеоасоційованих Мікроелементів При Хворобах Суглобів. Повідомлення ІІ. Мікроелементоз У Волоссі

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

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