Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: A randomized, double-blinded, placebo-controlled clinical trial

Heikkilä, Helka; Hielm‐Björkman, Anna; Morelius, Mikael; Larsen, Stig; Honkavaara, Juhana; Innes, John F.; Laitinen‐Vapaavuori, Outi

doi:10.1016/j.tvjl.2014.01.020

Cited by 40 publications

(40 citation statements)

References 39 publications

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“…Intra-articular injection of BoNT A reduced joint pain in osteoarthritic dogs in our recent placebo-controlled, double-blinded clinical trial [30]. Similar results have been reported in human patients with arthritis [31–34], and in induced inflammatory arthritis in experimental horses and mice [31, 35].…”

Section: Introductionsupporting

confidence: 69%

“…Although we have previously reported significant improvement from baseline in the IA BoNT A group compared to the placebo group after treatment [30], the pain relief might not have been strong enough to be detected as a significant change in the pain mediators’ concentrations.…”

Section: Discussionmentioning

confidence: 95%

“…Intra-articular BoNT A reduces joint pain in osteoarthritic dogs [30] and human patients [31–33]. However, the antinociceptive mechanism of action of IA BoNT A in the joint is currently not known.…”

Section: Discussionmentioning

confidence: 99%

“…The dogs were included in our previous study on IA BoNT A in the treatment of osteoarthritic joint pain in dogs [30]. The study was approved by the Animal Experiment Board (ESAVI-2010-04178/Ym-23) and the Finnish Medicines Agency.…”

Section: Methodsmentioning

confidence: 99%

“…Also, the dogs were excluded if they had received any IA treatment, corticosteroids, or pentosan polysulphate injection in less than one month before the study, or treatment with nonsteroidal anti-inflammatory drugs or tetracyclines in less than 1 week before the study. The dogs were screened for participation in the study as described previously [30]. …”

Section: Methodsmentioning

confidence: 99%

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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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