A comparative study on the efficacy of rofecoxib in monoarticular arthritis induced by latex of Calotropis procera and Freund’s complete adjuvant

Abstract

The role of prostaglandins in Calotropis procera latex induced inflammation and hyperalgesia has been well established. The acute inflammation induced by the dried latex (DL) of this plant could be effectively ameliorated by standard anti-inflammatory drugs. In present study we have evaluated the efficacy of rofecoxib, a COX-2 inhibitor in monoarthritis induced by intra-articular injection of DL and compared it with that against Freund's Complete Adjuvant (FCA). DL and FCA were injected into the right ankle joint of the rat and the joint diameter was measured by a micrometer screw gauge on day 0, 4, 8, 12, 20 and 28. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test and compression test. The effect of rofecoxib was evaluated on these parameters in both the models. Both DL and FCA produced peak inflammation on day 4 that was associated with decreased pain threshold and functional impairment. Although rofecoxib was more effective in improving motility in the DL model, its effect on joint inflammation, hyperalgesia and stair climbing ability was comparable in both the models. Thus, our study indicates that DL induced monoarthritis could be used as a model for the screening and evaluation of anti-inflammatory and anti-arthritic drugs.

Sensory and vascular changes in a rat monoarthritis model: prophylactic and therapeutic effects of meloxicam

“…reduced post-mortem analysis of ankle circumference and reduced the number of animals showing resistance to joint flexion and extension. Kumar et al [33] reported that another COX-2 inhibitor, rofecoxib, reduced nociceptive scores in the dorsal flexion pain test and the compression test; Wilson et al [38] also reported that rofecoxib and etoricoxib reduced changes in joint diameter and weight bearing in this CFA model during days 13-17. Increases in paw volume and ankle diameter have also been reported to be reduced by systemic administration of a selective prostaglandin E receptor 4 agonist given 24 h and 4 weeks after model induction [62].…”

“…Meloxicam is a potent antiinflammatory agent that is commonly prescribed to treat arthritic conditions [29,30]. Moreover, inhibition of COX-2 has beneficial effects on nociceptive scores in animal models of inflammatory joint disease [31][32][33]. However, most studies have examined only the effects of acute inhibition of COX-2 [32,33] and longer treatment regimens measured effects only during the early phase of model development and on a restricted number of functional readouts.…”

Projection of Exposure and Efficacious Dose Prior to First-in-Human Studies: How Successful Have We Been?

“…In oncology, for example, nude mice transplanted with human xenografts are routinely used to assess the in vivo efficacy of anti-tumor agents (12,13). In immunology, rodents with arthritis, induced by agents such as collagen or adjuvant, are also common (14)(15)(16). Compounds acting on the central nervous system are evaluated similarly in various behavioral animal models, with a focus on brain penetration and target (e.g., receptor) occupancy (17,18).…”

Dexamethasone Release from Glutaraldehyde Cross-Linked Chitosan Microspheres: In Vitro/In Vivo Studies and Non-Clinical Parameters Response in Rat Arthritic Model

“…At first day, 100 µL of CFA was injected into the paw of the right hind limb of each rat except the normal control (Kumar et al, 2006). For 15 days the rats were housed without treatment to maintain the full development of inflammatory arthritic condition.…”