Effects of Intra-articular Botulinum Toxin Type A in an Equine Model of Acute Synovitis

Depuy, Tracy; Howard, Rick D.; Keegan, Kevin G.; Wilson, David A.; Kramer, Joanne; Cook, James L.; Childers, Martin K.

doi:10.1097/phm.0b013e3181157718

Cited by 29 publications

(23 citation statements)

References 38 publications

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“…Similar results have been reported in human patients with arthritis [31–34], and in induced inflammatory arthritis in experimental horses and mice [31, 35]. Despite these promising results, the mechanism of the antinociceptive action of the toxin inside the joint has not been previously investigated.…”

Section: Introductionsupporting

confidence: 67%

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint

et al. 2017

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BackgroundRecently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE2 between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE2 concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated.ResultsThere was no significant change from baseline in SP or PGE2 after IA BoNT A. Synovial fluid PGE2 was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2 correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples.ConclusionsThe results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE2. Synovial fluid PGE2, but not SP, could be a marker for chronic osteoarthritis and pain in dogs.

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Section: Introductionsupporting

confidence: 67%

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint

et al. 2017

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“…Comparative studies with other models are lacking, and little information is available regarding reIL-1b's ability to induce predictable inflammation in the joint. The reIL-1b product has only recently become available and the in vivo use of intra-articular reIL-1b has only been reported once 26 with results limited to defining inflammatory effects. Therefore, this study was aimed at comparing reIL-1b to LPS as an in vivo synovitis model and exploring the potential of reIL-1b as a reversible model of OA.…”

Section: Discussionmentioning

confidence: 98%

“…We administered 100 ng of reIL-1b as we believed that this dose would induce a robust inflammatory response that was temporary and not severe enough to require rescue analgesic, and had been the reIL-1b dose used in a previous in vivo study 26 . While a reIL-1b dose of 0.1 ng/ml was reported to stimulate GAG release from equine cartilage explants 24 in vitro, a 6-fold increase in PGE 2 release was reported in the same study for 10 ng/ml of reIL-1b.…”

Section: Discussionmentioning

confidence: 99%

“…The reIL-1b group received 100 ng of reIL-1b (R&D Systems) in sterile PBS. The reIL-1b dose has been previously used in in vivo 26 and in vitro 24 models to elicit measurable inflammatory responses. As a control, each horse received an injection of sterile PBS into the contra-lateral carpal joint.…”

Section: Experimental Design and Induction Of Temporary Carpal Synovitismentioning

confidence: 99%

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Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide

Ross

Kisiday

Hess

et al. 2012

Osteoarthritis and Cartilage

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Injections of reIL-1β into equine carpal joints resulted in a transient inflammatory response that was similar in severity to the LPS injection, causing increased expression of certain deleterious mediators in joint tissues at 8 h. Given that IL-1β is a known critical mediator of traumatic arthritis and OA, this humane and temporary model may be useful in evaluating therapeutics that act against early stages of joint disease.

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“…Lipopolysaccharide [15], botulinum toxin [16], forced exercise [17], osteochondral fragment-exercise mode [18].…”

Section: Introductionmentioning

confidence: 99%

Iodoacetate and allogenous cartilage particles as models for arthritis induction in equine

Elmesiry¹,

Seleim

Cullis-Hill³

2014

International Journal of Veterinary Science and Medicine

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Experimental models of osteoarthritis (OA) have been widely developed in different animal species, because of the high incidence of osteoarthritis diseases in humans and animals. To date, no ideal OA animal model has been reported. The present study compare different osteoarthritis models to determine which one is suitable for inducing experimental equine OA. Fifteen donkeys were divided into three equal groups (n = 5). The radio carpal joints of the right forelimb of 15 donkeys were injected with 25 mg monoiodoacetate (MIA) (group A), 50 mg allogenous cartilage particles (ACP) (group B), or vehicle solution (group C) over a period of 70 days. Osteoarthritis induction was evaluated weekly through lameness score, carpal circumference, joint flexion angel, synovial fluid analysis (total protein and WBC count), and radiology. Animal were euthanized and joints histopathology were performed at 70 days. Lameness score and joint circumference was increased in both group A and B however joint flexion angel was decreased compared to group C (p < 0.05). Osteophytes were observed in MIA injected joints only accompanied with subchondral bone sclerosis. Cartilage damage was observed grossly and histologically in Group A together with synovial membrane fibrosis. Group B had on cartilage damage grossly however histological examination revealed some cartilage surface discontinuity with synovial membrane edema. Injection of monoiodoacetate in the donkey is a successful model to create the acute clinical signs of joint disease as well as cartilage damage. However, allogenous cartilage particles injection need more investigation to be applied. ª 2014 Faculty of Veterinary Medicine, Cairo University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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Effects of Intra-articular Botulinum Toxin Type A in an Equine Model of Acute Synovitis

Abstract: Our findings support the idea that BoNT-A can attenuate lameness in an equine model of acute synovitis. Our findings further suggest that BoNT-A might be a potential new treatment for painful arthritis; this warrants further study.

Cited by 29 publications

References 38 publications

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint

Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide

Iodoacetate and allogenous cartilage particles as models for arthritis induction in equine

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