The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint.
BACKGROUND
Recently, 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 PGE2between 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 PGE2concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated.


RESULTS
There was no significant change from baseline in SP or PGE2after IA BoNT A. Synovial fluid PGE2was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2correlated with osteoarthritic pain. No associations were found between SP or PGE2and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples.


CONCLUSIONS
The 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.
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, Helsinki, 00014, Finland. helka.heikkila@helsinki.fi.
Helka M
HM
Heikkilä
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, Helsinki, 00014, Finland.
Anna K
AK
Hielm-Björkman
Department of Musculoskeletal Biology, Institute of Aging and Chronic Disease and School of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK.|Present address: ChesterGates Referral Hospital, CVS Vets Ltd., Units E and F Telford Court, Chestergates Road, Chester, CH1 6LT, UK.
John F
JF
Innes
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, Helsinki, 00014, Finland.
Outi M
OM
Laitinen-Vapaavuori
D000818:Animals; D018771:Arthralgia / Q000188:drug therapy / Q000662:veterinary*; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism*; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D007270:Injections, Intra-Articular / Q000662:veterinary; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary; D059408:Pain Management / Q000662:veterinary; D013373:Substance P / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D019274:Botulinum Toxins, Type A; D015232:Dinoprostone
Dog; Intra-articular botulinum toxin A; Osteoarthritis; Pain; Prostaglandin E2; Substance P; Tumor necrosis factor alpha