Zymosan-induced arthritis in rats II. Effects of anti-inflammatory drugs

Gegout, P.; Gillet, Pierre; Terlain, Bernard; Netter, Patrick

doi:10.1016/0024-3205(95)98583-2

Cited by 20 publications

(23 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Examination of rat knees showed that, in contrast to NPX, DEX exerted a dramatic antiinflammatory effect, but prevented normal animal growth and weight gain starting from day 14, as has been reported previously (31)(32)(33). This observation is consistent with the cartilage thinning relative to controls found on US images and on histologic sections on day 21.…”

Section: Discussionsupporting

confidence: 79%

Effects of antiinflammatory drugs on arthritic cartilage: A high‐frequency quantitative ultrasound study in rats

Jaffre¹,

Watrin²,

Lœuille³

et al. 2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To evaluate the ability of 55-MHz quantitative ultrasound (US) to detect the in vivo effects of experimental arthritis, as well as those of two antiinflammatory drugs, naproxen (NPX) and dexamethasone (DEX), on cartilage and subchondral bone.Methods. Arthritis was induced in both knees of 108 rats by intraarticular injection of zymosan (ZYM). Two groups of arthritic rats (n ‫؍‬ 36 per group) were treated daily with either NPX (10 mg/kg/day) or DEX (0.1 mg/kg/day). Using a 3-dimensional US microscope, patellae were explored in vitro on days 5, 14, and 21 after injections. US assessment included the analysis of quantitative indices of local modifications involving cartilage and bone: integrated reflection coefficient (IRC) from the cartilage surface and apparent integrated backscatter from the cartilage internal structure (cartilage matrix) (AIB cartilage ) and the cartilage-bone interface (AIB bone ).Results. ZYM induced articular surface fibrillation that resulted in a decrease in IRC at all times (P < 0.02) and in an increase in AIB bone on days 5 and 14 (P < 0.005). Fibrillation was not changed by NPX administration, while it disappeared following DEX treatment. Cartilage-bone interface alterations were prevented by DEX and partially compensated for by NPX. Cartilage matrix echogenicity decreased with time in all groups due to maturation (P < 0.05), except in DEX-treated rats.Conclusion. Quantitative 55 MHz US allowed detection of early cartilage and bone lesions due to experimental arthritis, and also allowed detection of the effects of antiinflammatory drugs. NPX seemed to have an effect on subchondral bone lesions, but not on cartilage. DEX appeared to repair articular surface and bone, but prevented animal growth and cartilage maturation.In rheumatoid arthritis (RA), synovial inflammation and pannus releasing matrix metalloproteinases, oxygen-derived free radicals, cytokines, and prostaglandins degrade articular cartilage. These mediators provoke proteoglycan (PG) synthesis inhibition, cartilage destruction, bone erosions, and ancillary progressive articular loss of function (1,2). They are also responsible for the swelling and pain in arthritic joints. Nonsteroidal antiinflammatory drugs (NSAIDs) and oral steroids reduce the RA symptoms of joint pain and swelling. However, evidence in clinics and from in vitro studies that NSAIDs and steroids can prevent the progression of chronic, destructive arthritis is both sparse and controversial (3-7). Furthermore, most in vitro studies rely on destructive techniques (e.g., histology and biochemistry), and the criteria for determining cartilage degradation remain qualitative.There is increasing interest in the use of ultrasonography in rheumatology, since ultrasound (US) is noninvasive, safe, more accurate than clinical evaluation of synovitis and cartilage thickness in small joints, and can be used repeatedly in RA patients (8). Recent research suggests that high-frequency US may also serve ex vivo as a useful means for the investigation of cartilage ma...

show abstract

Section: Discussionsupporting

confidence: 79%

Effects of antiinflammatory drugs on arthritic cartilage: A high‐frequency quantitative ultrasound study in rats

Jaffre¹,

Watrin²,

Lœuille³

et al. 2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…The dose-effect relationships for these drugs are similar in this model compared with those obtained in more traditional antihyperalgesia tests (Table 1), such as the carrageenan-induced thermal and mechanical hyperalgesia assays (Gegout et al, 1995;Chan et al, 1999;Harris et al, 2004). These results indicate that RSAA is pharmacologically well validated with clinically useful analgesic agents.…”

Section: Discussionmentioning

confidence: 54%

Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats

Matson¹,

Broom²,

Carson³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The majority of rodent models used to evaluate analgesic drug effects rely on evoked measures of nociceptive thresholds as primary outcomes. These approaches are often time-consuming, requiring extensive habituation sessions and repeated presentations of eliciting stimuli, and are prone to false-positive outcomes due to sedation or tester subjectivity. Here, we describe the reduction of spontaneous activity by adjuvant (RSAA) model as an objective and quantifiable behavioral model of inflammatory pain that can predict the analgesic activity of a variety of agents following single-dose administration. In the RSAA model, activity was measured in nonhabituated rats using standard, photocell-based monitors. Bilateral inflammation of the knee joints by complete Freund's adjuvant (CFA) reduced the normal level of activity (horizontal locomotion and vertical rearing) by ϳ60% in a novel environment. This reduction in activity was dose-dependently reversed by ibuprofen, rofecoxib, celecoxib, piroxicam, and dexamethasone, whereas gabapentin and amitriptyline were inactive. Morphine significantly reversed the activity-suppressing effects of CFA, at 1 mg/kg s.c., but at higher doses locomotor activity progressively declined, coincident with the induction of sedation. In contrast to morphine and anti-inflammatory therapies, amphetamine did not affect vertical rearing, even though it increased horizontal locomotion. Thus, unlike standard measures of analgesia such as alteration in thermal or mechanical sensitivity, the RSAA model operationally defines analgesia as a drug-induced increase in spontaneous behavior (vertical rearing in a novel environment). We conclude that the RSAA model is valuable as an objective measure of analgesic efficacy that is not dependent on an evoked stimulus response.Due to the emotional and subjective nature of pain, the preclinical testing of novel analgesic agents has proven to be a challenging undertaking. The measurement of nociception and subsequent antinociceptive properties of compounds has traditionally been performed in assays that measure an animal's responsiveness to differing evoked nociceptive stimuli. Such assays have to be amenable to displaying either allodynia or hyperalgesia resulting from inflammatory or neuropathic pain induction, as well as detecting the ability of drugs to reverse this hypersensitivity.The most widely used analgesia assays assess mechanical and thermal sensitivity. These include mechanical/tactile allodynia measured by von Frey filaments (Chaplan et al., 1994), mechanical hyperalgesia measured by the RandallSelitto paw pressure test (Randal and Selitto, 1957), and heat hyperalgesia measured by the Hargreaves radiant heat assay (Hargreaves et al., 1988). These standard rodent hypersensitivity models may be potentially biased by rater subjectivity (e.g., von Frey test) or require exposure to a manually applied noxious stimulus (e.g., paw pressure test, radiant heat assay), and all rely on an evoked measure of sensitivity. Furthermore, although these mode...

show abstract

“…Gegout et al (21) observed that an intra-articular injection of zymosan increased the body temperature that was reduced by indomethacin, a nonselective COX inhibitor. Supporting these findings (21) and their implication of COX-2 in the production Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Frasnelli et al (19) demonstrated that Toll-like receptor (TLR) 2 is the major pathway of proinflammatory signaling in zymosan-induced arthritis in mice. Furthermore, this stimulus has been used in the investigation of other aspects of arthritis-associated inflammatory response, including loss of mobility, articular hyperalgesia, edema, and fever (20,21,46,47,52).…”

Section: Discussionmentioning

confidence: 99%

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Kanashiro¹,

Pessini²,

Machado³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Kanashiro A, Pessini AC, Machado RR, Malvar DC, Aguiar FA, Soares DM, Vale ML, Souza GEP. Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats. Am J Physiol Regul Integr Comp Physiol 296: R1631-R1640, 2009. First published February 25, 2009 doi:10.1152/ajpregu.90527.2008.-The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE2 concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE 2 concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60 -240 mg/kg), and paracetamol (100 -200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE 2 concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE2 in this response.

show abstract

Zymosan-induced arthritis in rats II. Effects of anti-inflammatory drugs

Cited by 20 publications

References 15 publications

Effects of antiinflammatory drugs on arthritic cartilage: A high‐frequency quantitative ultrasound study in rats

Effects of antiinflammatory drugs on arthritic cartilage: A high‐frequency quantitative ultrasound study in rats

Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Contact Info

Product

Resources

About