Abstract
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.
Highlights
Intra-articular botulinum toxin A (IA Botulinum neurotoxin A (BoNT A)) has been shown to reduce joint pain in osteoarthritic dogs
There were no significant differences between the groups of dogs in age, weight, gender, duration of lameness, or sampled joint (Table 1)
Substance P analysis In osteoarthritic dogs, synovial fluid (SF) and serum substance P (SP) concentrations were not statistically different in the IA BoNT A group compared to the placebo group at baseline (P = 0.180 and P = 0.683, respectively)
Summary
Intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. 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. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Increased level of SP in synovial fluid (SF) has been related both to OA and to joint pain in horses [6, 7], and the upregulation of SP-positive nerve fibers in the joint is associated with painful OA in human patients [8]. Nerve fibers containing SP have been found in various joint structures of dogs [9,10,11]; and recently, the concentration of SP in the spinal cord has been associated with central sensitization and pain in dogs with experimental OA [12]. To our knowledge the SF SP concentration and its association with osteoarthritic pain have not been studied in this species
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