Intra-articular botulinum toxin A in treatment of osteoarthritic joint pain in dogs

Helka Maaria Heikkilä

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Osteoarthritis (OA) is considered to be the leading cause of chronic pain in dogs. Oral medication is the mainstay of pain treatment in canine OA, but it can provide insufficient pain relief and intolerable adverse events. Therefore, new treatment modalities are needed for dogs suffering from osteoarthritic pain. Intra-articularly injected botulinum toxin A (IA BoNT A) has shown efficacy in treatment of joint pain in arthritic human patients. The mechanism of the antinociceptive action of IA BoNT A has not been studied in vivo and its adverse effects have not been thoroughly investigated.
Our aim was to study the antinociceptive efficacy of IA BoNT A in osteoarthritic dogs and to investigate the effect it has on their pain mediators. Also, we wanted to compare the pain mediators between osteoarthritic and non-osteoarthritic joints and reveal any associations with osteoarthritic pain. Our aim was also to investigate the adverse effects of IA BoNT A and to study whether the toxin spreads from the joint.
We investigated the antinociceptive efficacy of IA BoNT A in a randomized, double-blinded, placebo-controlled, 12-week clinical trial in 35 client-owned osteoarthritic dogs after an injection of either IA BoNT A or placebo into the stifle, hip, or elbow joint. We detected significant improvement in the ground reaction forces and Helsinki Chronic Pain Index in the IA BoNT A group. There was also a significant difference in the improvement of the ground reaction forces between the IA BoNT A and placebo groups.
We measured substance P (SP), prostaglandin E2 (PGE2), and tumour necrosis factor-alpha (TNF-α) from the synovial fluid (SF) and serum of the 35 osteoarthritic dogs and also analysed SF SP and PGE2 from 13 non-osteoarthritic control joints. IA BoNT A did not affect SF or serum SP or PGE2. TNF-α was not detectable in our samples. SF PGE2 correlated with osteoarthritic joint pain and was significantly higher in osteoarthritic than in non-osteoarthritic joints.
We investigated the adverse effects of IA BoNT A in a randomized, placebo-controlled, blinded trial in six healthy laboratory beagle dogs after IA BoNT A and placebo injections into the stifle joints. No significant clinical, cytological, or histopathological adverse effects were detected 12 weeks after the injections, but changes in the electrophysiological recordings in two dogs suggested possible spread of the toxin.
Our results indicate that IA BoNT A has efficacy in the treatment of osteoarthritic joint pain in dogs. The antinociceptive effect of IA BoNT A inside the joint seems not to be related to the inhibition in the release of SP or PGE2. SF PGE2 could be a marker of chronic OA and pain in dogs. IA BoNT A does not cause clinical, cytological, or histopathological adverse effects in healthy dogs, although the toxin may spread from the joint.
Original languageEnglish
Supervisors/Advisors
  • Vapaavuori, Outi, Supervisor
  • Hielm-Björkman, Anna, Supervisor
  • Innes, John F., Supervisor, External person
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-3845-3
Electronic ISBNs978-951-51-3846-0
Publication statusPublished - 2017
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 413 Veterinary science

Cite this

Heikkilä, Helka Maaria. / Intra-articular botulinum toxin A in treatment of osteoarthritic joint pain in dogs. Helsinki : Unigrafia oy, 2017. 103 p.
@phdthesis{738547dc66d347b18d1e2ce46dc7168a,
title = "Intra-articular botulinum toxin A in treatment of osteoarthritic joint pain in dogs",
abstract = "Osteoarthritis (OA) is considered to be the leading cause of chronic pain in dogs. Oral medication is the mainstay of pain treatment in canine OA, but it can provide insufficient pain relief and intolerable adverse events. Therefore, new treatment modalities are needed for dogs suffering from osteoarthritic pain. Intra-articularly injected botulinum toxin A (IA BoNT A) has shown efficacy in treatment of joint pain in arthritic human patients. The mechanism of the antinociceptive action of IA BoNT A has not been studied in vivo and its adverse effects have not been thoroughly investigated.Our aim was to study the antinociceptive efficacy of IA BoNT A in osteoarthritic dogs and to investigate the effect it has on their pain mediators. Also, we wanted to compare the pain mediators between osteoarthritic and non-osteoarthritic joints and reveal any associations with osteoarthritic pain. Our aim was also to investigate the adverse effects of IA BoNT A and to study whether the toxin spreads from the joint. We investigated the antinociceptive efficacy of IA BoNT A in a randomized, double-blinded, placebo-controlled, 12-week clinical trial in 35 client-owned osteoarthritic dogs after an injection of either IA BoNT A or placebo into the stifle, hip, or elbow joint. We detected significant improvement in the ground reaction forces and Helsinki Chronic Pain Index in the IA BoNT A group. There was also a significant difference in the improvement of the ground reaction forces between the IA BoNT A and placebo groups. We measured substance P (SP), prostaglandin E2 (PGE2), and tumour necrosis factor-alpha (TNF-α) from the synovial fluid (SF) and serum of the 35 osteoarthritic dogs and also analysed SF SP and PGE2 from 13 non-osteoarthritic control joints. IA BoNT A did not affect SF or serum SP or PGE2. TNF-α was not detectable in our samples. SF PGE2 correlated with osteoarthritic joint pain and was significantly higher in osteoarthritic than in non-osteoarthritic joints. We investigated the adverse effects of IA BoNT A in a randomized, placebo-controlled, blinded trial in six healthy laboratory beagle dogs after IA BoNT A and placebo injections into the stifle joints. No significant clinical, cytological, or histopathological adverse effects were detected 12 weeks after the injections, but changes in the electrophysiological recordings in two dogs suggested possible spread of the toxin.Our results indicate that IA BoNT A has efficacy in the treatment of osteoarthritic joint pain in dogs. The antinociceptive effect of IA BoNT A inside the joint seems not to be related to the inhibition in the release of SP or PGE2. SF PGE2 could be a marker of chronic OA and pain in dogs. IA BoNT A does not cause clinical, cytological, or histopathological adverse effects in healthy dogs, although the toxin may spread from the joint.",
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Intra-articular botulinum toxin A in treatment of osteoarthritic joint pain in dogs. / Heikkilä, Helka Maaria.

Helsinki : Unigrafia oy, 2017. 103 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Intra-articular botulinum toxin A in treatment of osteoarthritic joint pain in dogs

AU - Heikkilä, Helka Maaria

PY - 2017

Y1 - 2017

N2 - Osteoarthritis (OA) is considered to be the leading cause of chronic pain in dogs. Oral medication is the mainstay of pain treatment in canine OA, but it can provide insufficient pain relief and intolerable adverse events. Therefore, new treatment modalities are needed for dogs suffering from osteoarthritic pain. Intra-articularly injected botulinum toxin A (IA BoNT A) has shown efficacy in treatment of joint pain in arthritic human patients. The mechanism of the antinociceptive action of IA BoNT A has not been studied in vivo and its adverse effects have not been thoroughly investigated.Our aim was to study the antinociceptive efficacy of IA BoNT A in osteoarthritic dogs and to investigate the effect it has on their pain mediators. Also, we wanted to compare the pain mediators between osteoarthritic and non-osteoarthritic joints and reveal any associations with osteoarthritic pain. Our aim was also to investigate the adverse effects of IA BoNT A and to study whether the toxin spreads from the joint. We investigated the antinociceptive efficacy of IA BoNT A in a randomized, double-blinded, placebo-controlled, 12-week clinical trial in 35 client-owned osteoarthritic dogs after an injection of either IA BoNT A or placebo into the stifle, hip, or elbow joint. We detected significant improvement in the ground reaction forces and Helsinki Chronic Pain Index in the IA BoNT A group. There was also a significant difference in the improvement of the ground reaction forces between the IA BoNT A and placebo groups. We measured substance P (SP), prostaglandin E2 (PGE2), and tumour necrosis factor-alpha (TNF-α) from the synovial fluid (SF) and serum of the 35 osteoarthritic dogs and also analysed SF SP and PGE2 from 13 non-osteoarthritic control joints. IA BoNT A did not affect SF or serum SP or PGE2. TNF-α was not detectable in our samples. SF PGE2 correlated with osteoarthritic joint pain and was significantly higher in osteoarthritic than in non-osteoarthritic joints. We investigated the adverse effects of IA BoNT A in a randomized, placebo-controlled, blinded trial in six healthy laboratory beagle dogs after IA BoNT A and placebo injections into the stifle joints. No significant clinical, cytological, or histopathological adverse effects were detected 12 weeks after the injections, but changes in the electrophysiological recordings in two dogs suggested possible spread of the toxin.Our results indicate that IA BoNT A has efficacy in the treatment of osteoarthritic joint pain in dogs. The antinociceptive effect of IA BoNT A inside the joint seems not to be related to the inhibition in the release of SP or PGE2. SF PGE2 could be a marker of chronic OA and pain in dogs. IA BoNT A does not cause clinical, cytological, or histopathological adverse effects in healthy dogs, although the toxin may spread from the joint.

AB - Osteoarthritis (OA) is considered to be the leading cause of chronic pain in dogs. Oral medication is the mainstay of pain treatment in canine OA, but it can provide insufficient pain relief and intolerable adverse events. Therefore, new treatment modalities are needed for dogs suffering from osteoarthritic pain. Intra-articularly injected botulinum toxin A (IA BoNT A) has shown efficacy in treatment of joint pain in arthritic human patients. The mechanism of the antinociceptive action of IA BoNT A has not been studied in vivo and its adverse effects have not been thoroughly investigated.Our aim was to study the antinociceptive efficacy of IA BoNT A in osteoarthritic dogs and to investigate the effect it has on their pain mediators. Also, we wanted to compare the pain mediators between osteoarthritic and non-osteoarthritic joints and reveal any associations with osteoarthritic pain. Our aim was also to investigate the adverse effects of IA BoNT A and to study whether the toxin spreads from the joint. We investigated the antinociceptive efficacy of IA BoNT A in a randomized, double-blinded, placebo-controlled, 12-week clinical trial in 35 client-owned osteoarthritic dogs after an injection of either IA BoNT A or placebo into the stifle, hip, or elbow joint. We detected significant improvement in the ground reaction forces and Helsinki Chronic Pain Index in the IA BoNT A group. There was also a significant difference in the improvement of the ground reaction forces between the IA BoNT A and placebo groups. We measured substance P (SP), prostaglandin E2 (PGE2), and tumour necrosis factor-alpha (TNF-α) from the synovial fluid (SF) and serum of the 35 osteoarthritic dogs and also analysed SF SP and PGE2 from 13 non-osteoarthritic control joints. IA BoNT A did not affect SF or serum SP or PGE2. TNF-α was not detectable in our samples. SF PGE2 correlated with osteoarthritic joint pain and was significantly higher in osteoarthritic than in non-osteoarthritic joints. We investigated the adverse effects of IA BoNT A in a randomized, placebo-controlled, blinded trial in six healthy laboratory beagle dogs after IA BoNT A and placebo injections into the stifle joints. No significant clinical, cytological, or histopathological adverse effects were detected 12 weeks after the injections, but changes in the electrophysiological recordings in two dogs suggested possible spread of the toxin.Our results indicate that IA BoNT A has efficacy in the treatment of osteoarthritic joint pain in dogs. The antinociceptive effect of IA BoNT A inside the joint seems not to be related to the inhibition in the release of SP or PGE2. SF PGE2 could be a marker of chronic OA and pain in dogs. IA BoNT A does not cause clinical, cytological, or histopathological adverse effects in healthy dogs, although the toxin may spread from the joint.

KW - 413 Veterinary science

M3 - Doctoral Thesis

SN - 978-951-51-3845-3

PB - Unigrafia oy

CY - Helsinki

ER -