Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

PLoS One. 2015 Oct 20;10(10):e0140439. doi: 10.1371/journal.pone.0140439. eCollection 2015.

Abstract

The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Animals
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / pharmacology*
  • Electric Stimulation
  • Electrophysiological Phenomena / drug effects
  • Hindlimb / drug effects
  • Hindlimb / physiology
  • Injections, Intramuscular
  • Lactic Acid / pharmacology
  • Male
  • Motor Activity / drug effects*
  • Muscle Contraction / drug effects
  • Muscle Fatigue / drug effects
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Neurotoxins / administration & dosage
  • Neurotoxins / pharmacology
  • Potassium Chloride / pharmacology
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Tendons / drug effects
  • Tendons / physiology
  • Time Factors

Substances

  • Neurotoxins
  • Lactic Acid
  • Potassium Chloride
  • Botulinum Toxins, Type A

Grant support

This work was supported by funding from Aix-Marseille Université (AMU) and the Centre National de la Recherche Scientifique (CNRS).