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

PLoS One. 2018 Jan 10;13(1):e0191043. doi: 10.1371/journal.pone.0191043. eCollection 2018.

Abstract

Objective: To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection.

Methods: A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed.

Results: Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin.

Conclusion: Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / adverse effects*
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Dogs
  • Female
  • Placebos

Substances

  • Placebos
  • Botulinum Toxins, Type A

Grants and funding

One of the authors (HMH) received a grant from the Finnish Veterinary Foundation (http://www.etts.fi/en/introduction.html) to conduct this study. This study was also supported by the Department of Equine and Small Animal Diseases of the Faculty of Veterinary Medicine in the University of Helsinki. One of the authors, Jouni Junnila, is an employee of Oy 4Pharma Ltd which provides statistical services to clinical research. Oy 4Pharma Ltd was hired by our research group to help in designing the study and to do the statistical analysis. Oy 4Pharma Ltd did not have any additional role in decision to publish the manuscript. The specific role of the author (JJ) is articulated in the ‘author contributions’ section.