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

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.

Intra-articular botulinum toxin A (BoNT/A) for pain management in dogs with osteoarthritis secondary to hip dysplasia: A randomized controlled clinical trial

“…In the present study, no serious adverse events were noted. This result supports previous studies that reported minimal adverse effects following IA BoNT-A injection in dogs [12,13,14,15].…”

“…Thus, when administered by IA route, BoNT/A may suppress the release of neuropeptides at the nociceptive nerve endings, directly reducing the peripheral sensitisation and, indirectly, the central sensitisation [24]. However, a recent study did not find any significant reduction in the synovial fluid concentrations of substance P and prostaglandin E2 from two to eight weeks after an IA BoNT/A injection in osteoarthritic dogs [13].…”

Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial

“…The rationale behind the use of IA BoNT/A in the treatment of OA pain is its ability to inhibit the release of neurotransmitter substance P [ 14 , 15 ], calcitonin gene-related peptide [ 16 ], and glutamate [ 17 , 18 ], which are also involved in the sensation of pain in OA [ 19 , 20 ]. However in our recent study, IA BoNT/A did not affect the concentration of substance P inside a joint ([ 21 ].…”

Effects of photobiomodulation associated with chitosan viscosupplementation for osteoarthritis: an in vitro and in vivo study

“…It has been known that excess production of the inflammatory cytokines plays vital roles in the development of OA (Vincent et al 2013). Among these cytokines, TNF-α has been shown to perform a pivotal role in OA as it contributes to cartilage matrix degradation (Heikkilä et al 2017). TNF-α could activate inflammatory cells, which subsequently synthesize others pro-inflammatory chemokines to maintain inflammation in the development of OA (Mabey et al 2016).…”