Quantitative evaluation of an experimental inflammation induced with Freund's Complete Adjuvant in dogs

Botrel, M.A.; Haak, T.; Legrand, Catherine; Concordet, Didier; Chevalier, Robert L.; Toutain, Pierre‐Louis

doi:10.1016/1056-8719(94)90055-8

Cited by 21 publications

(20 citation statements)

References 10 publications

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“…Previous studies showed that the NO level was increased during inflammatory disorders (Botrel et al, 1994;Rawls et al, 2004a). The response of smooth muscle of the vessels to the α-receptors antagonist is influenced by the released agents from endothelium of vessels (Botrel et al, 1994), whereas NO decreased vasoconstriction response in inflamed joint, thus, the CCBs may in turn causes decrease in blood flow by al-teration in the production of NO (Lam and Ferrell, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The response of smooth muscle of the vessels to the α-receptors antagonist is influenced by the released agents from endothelium of vessels (Botrel et al, 1994), whereas NO decreased vasoconstriction response in inflamed joint, thus, the CCBs may in turn causes decrease in blood flow by al-teration in the production of NO (Lam and Ferrell, 1993). It has also been reported that in acute (Rosen, 1989) and chronic (Morgan et al, 1978) inflammation in rat knee, the constriction response to the knee sympathic stimuli-tion has decreased, so probably CCBs, prevented the decrease in responsiveness by local changes in the inflamed joint.…”

Section: Discussionmentioning

confidence: 99%

“…The constitutional mechanism for increasing blood flow in a chronic inflamed joint is yet to be clarified. Few reports showed that it could be due to the decreased sympathetic tonicity of the vessels (Boston et al, 2004), changes in beta-adrenergic receptors profile (Botrel et al, 1994), and the decrease in knee vessels in response to phenylephrine and overproduction of nitric oxide (NO). It has been revealed that this change is due to the altered secretion and release of local vessels relaxating mediators from the inflamed cells or sensory nerve ends, whereas calcitonin gene-related peptide (CGRP) and substance P that are released from the sensory nerves ends, caused the neurogenic dilatation of the vessels (Fahim et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Calcium channel blockers attenuate chronic inflammation in rat knee joints

Rahmani¹,

Allahtavakoli²,

Mahmoodi³

et al. 2013

Afr. J. Pharm. Pharmacol.

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Previous studies demonstrated therapeutic effects for calcium channel blockers (CCBs) in control of acute inflammation. There are little reports on the effect of these blockers on chronic inflammation. In this study, we investigated the effects of CCBs on chronic inflammation using complete Ferund's adjuvant (CFA) induced inflammation in the rat knee joints. This experimental study was carried out on 80 male Wistar rats. Calcium channel blockers (verapamil and nifedipine) were used in doses of 100 and 800 µg/kg. For induction of chronic inflammation, CFA (0.2 ml) was injected into the right knee joint. The changes in blood flow, and local temperature of the animal's knee joint were measured by laser Doppler flowmetry and also the knee diameter was measured by a caliper, on 0, 7, 14, 21, and 28 days after CFA injection. CFA injection significantly increased blood flow from day 1 to 28 as compared to the day 0. Administration of both verapamil and nifedipine (100 and 800 µg/kg) significantly decreased the effect of CFA on increasing blood flow (all p < 0.05). Administration of both verapamil and nifedipine (100 and 800 µg/kg) significantly inhibited the effect of CFA on increasing knee temperature (all p < 0.05). Injection of CFA increased the knee joint diameter for all 28 days after injection. Both low and high doses of nifedipine and verapamil could inhibit the increased diameter that is induced by CFA injection (all p < 0.05). The effects of CCBs on measured parameter were comparable with the effect of ibuprofen (which is a standard anti-inflammatory drug) on these parameters. The results revealed that CCBs inhibited the increased rat knee blood flow, diameter and temperature in chronic inflammation induced by CFA. Therefore, the underlying mechanisms for reduction of chronic inflammation possibly are modulated by these blockers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Calcium channel blockers attenuate chronic inflammation in rat knee joints

Rahmani¹,

Allahtavakoli²,

Mahmoodi³

et al. 2013

Afr. J. Pharm. Pharmacol.

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“…Botrel and co-workers [391] investigated the reactions to Freund's complete adjuvant injected into the stifle joints of dogs and established that nimesulide had protective effects against bone and cartilage destruction in this model of periarthritis.…”

Section: In Vivo Effects Of Nimesulide On Cartilage and Bone In Expermentioning

confidence: 99%

Pharmacological properties of nimesulide

Rainsford

Bevilacqua

Dallegri³

et al. 2005

Nimesulide — Actions and Uses

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Arthritis [11] granuloma [11] Exudate Volume Leucocytes in Rats [11] DRUG ED 40 (CI) mg/kg/d ED 30 (CI) mg/kg ED 30 mg/kg ED 50 (Cl) mg/kgNimesulide 1.6 (0.07-38) 0.65 (0.18-2.3)~1.0~1.5 11 (3.9-28) Ibuprofen 75 (11-500) 45 (10-198) N/D N/D 16 (6.1-40) Indomethacin 0.8 (0.03-23) 1.2 (0.31-5.9)~0.3~0.2 1.1 (0.4-3.0) Ratio-Nimesulide/ 2.0 0.54 0.3 7.5 10.0 Indomethacin Nimesulide/ 0.021 0.014 N/D N/D 0.69 Ibuprofen CI = 95% confidence interval. N/D = not determined. 140 K. D. Rainsford et al.∑ Arachidonic acid metabolism, especially production of COX-2 derived prostaglandins and leukotrienes ∑ Proinflammatory cytokine production and actions, especially of tumour necrosis factor-a (TNFa) and interleukins (IL), 1, 6 and 8

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“…However, this model is of too short in duration (less than 24 h) to allow a PK/PD investigation for drugs having a duration of action of approximately 24 h. Likewise, the carrageenan-induced acute paw inflammation in dogs model proposed by Brooks et al (1991) was too short in duration for this purpose. This is why we developed a Freund's complete adjuvant osteoarthritis model, resulting in a sustained and relatively stable secondary inflammatory response (Botrel et al, 1994;Toutain et al, 2001). This Freund's model was scientifically attractive, allowing repeatable measurements of relevant clinical end points, but the inflammation was irreversible, and it was mandatory to sacrifice dogs for ethical reasons.…”

Section: Introductionmentioning

confidence: 99%

Paw Inflammation Model in Dogs for Preclinical Pharmacokinetic/Pharmacodynamic Investigations of Nonsteroidal Anti-Inflammatory Drugs

Jeunesse¹,

Bargues²,

Toutain³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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The goal of the present study was to develop and validate a new canine model of inflammation. The motivation was to make available a scientifically appropriate and ethically acceptable model to conduct pharmacokinetic/pharmacodynamic investigations for testing nonsteroidal anti-inflammatory drugs in dogs. A kaolin-induce paw inflammation model previously developed in cats was adapted to the dog. The paw inflammation developed within a few hours, reached maximum values 24 h and up to 3 days after kaolin administration, and then progressively resolved over 2 months. Five end points of clinical interest (body temperature, creeping time under a tunnel, paw withdrawal latency to a standardized thermal stimulus, lameness score, and vertical force developed during walking on a force plate) were measured regularly over the next 24 h and beyond to characterize the time development of the inflammation either in control conditions (placebo period) or after the administration of meloxicam (test period) according to a crossover design. Pharmacodynamic data were modeled using an indirect response pharmacokinetic/pharmacodynamic model. This model described three effects of meloxicam, namely, classic antiinflammatory, analgesic, and antipyretic effects. The mean plasma meloxicam IC 50 values were 210 ng/ml for the antipyretic effect, 390 ng/ml for the analgesic effect, and 546 ng/ml for the vertical force exerted by the paw on the ground as measured by force plates. These in vivo IC 50 values require approximately 80 (antipyretic effect) to 90% (all other effects) cyclooxygenase-2 inhibition as calculated ex vivo whole-blood assay data.

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Quantitative evaluation of an experimental inflammation induced with Freund's Complete Adjuvant in dogs

Cited by 21 publications

References 10 publications

Calcium channel blockers attenuate chronic inflammation in rat knee joints

Calcium channel blockers attenuate chronic inflammation in rat knee joints

Pharmacological properties of nimesulide

Paw Inflammation Model in Dogs for Preclinical Pharmacokinetic/Pharmacodynamic Investigations of Nonsteroidal Anti-Inflammatory Drugs

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