Dose-Finding in the Development of an LPS-Induced Model of Synovitis in Sheep

Abstract

Models of transient synovitis that can be controlled with antiinflammatory and analgesic drugs have been used to studypain amelioration. To this end, we aimed to determine the dose of intraarticularly administered E. coli LPS that inducedsigns of synovitis without systemic signs in clinically healthy male castrated sheep (n = 14). In phase 1, a single dose of LPS(0.5, 1.0, 1.5, or 2.0 ng in a total volume of 0.5 mL) was administered into the right stifle joint. In phase 2, a dose of LPS (1.0 or 2.0 μg) in 0.3 mL was administered to 4 naïve sheep. In phase 3, 4 sheep from phase 1 were inoculated after a 60 d washout period with either 0.5 or 1.0 μg of LPS. During the first 48 h after LPS administration, the following were performed: assessment of clinical parameters; scoring for lameness, pain on limb flexion, and local swelling; and ultrasonography of the joints were performed. The doses tested during phase 1 produced subtle signs. During phase 2, mild to moderate lameness with no evidence of systemic signs occurred at both doses. In phase 3, clinical responses were similar between the 0.5- and 1-μg doses. Signs of swelling were not observed at any time. Therefore, we consider the 0.5-μg to be the most appropriate for this model, because it was the lowest dose tested capable of causing lameness without signs of systemic inflammation in all animals.

Protective Effect of Cichorium Intybus Root Extract and Esculetin on Lipopolysaccharide-Induced Pain and Inflammation in Male Mice: A Potential Role for Tumor Necrosis Factor-α and Interleukin-1β

“…Previous studies have shown that systemic administration of LPS can lead to a generalized hyperalgesia [8]. Various mechanisms including the release of pro-in ammatory cytokines and glial cell activation have been proposed to be responsible for the LPS-induced hyperalgesia [7,8]. TNF-α and IL-1β are two essential cytokines involved in the in ammatory response as well as neuropathic pain induction.…”

“…The ability to mimic the clinical presentation of diseases such as pain, in animal models, is important to achieve reliable medical results [7]. Nowadays, bacterial lipopolysaccharide (LPS) is widely used worldwide for arrays of investigations such as modeling of diseases, in ammatory mechanism evaluation, psycho/neurologic and behavioral studies both in vivo and in vitro [7][8][9].…”

“…The ability to mimic the clinical presentation of diseases such as pain, in animal models, is important to achieve reliable medical results [7]. Nowadays, bacterial lipopolysaccharide (LPS) is widely used worldwide for arrays of investigations such as modeling of diseases, in ammatory mechanism evaluation, psycho/neurologic and behavioral studies both in vivo and in vitro [7][8][9]. Moreover, It is also considered as a causative agent of different types of pain and currently is used to induce animal models of pain enhancement sensitivity, hyperalgesia and allodynia [7,8].…”

“…Nowadays, bacterial lipopolysaccharide (LPS) is widely used worldwide for arrays of investigations such as modeling of diseases, in ammatory mechanism evaluation, psycho/neurologic and behavioral studies both in vivo and in vitro [7][8][9]. Moreover, It is also considered as a causative agent of different types of pain and currently is used to induce animal models of pain enhancement sensitivity, hyperalgesia and allodynia [7,8]. Systemic LPS exposure leads to in ammatory responses in serum and spinal cord of rats.…”

No adverse effects on periarticular tissue by intra‐articular vitamin D analogue calcipotriol in a reduced‐dose zymosan‐induced arthritis model in rats

“…In previous literature, there are models of self-limiting synovitis, such as intra-articular lipopolysaccharide injection in horses 29 or sheep-these kinds of settings can be used in tests of analgesics. 30 In arthritis research, multiple different arthritis models in animals have been used, but a single definitive method to model OA does not exist. 31 In rats, spontaneous OA is rare apart from minor focal changes.…”