128
· DOS Abstracts
Reduced force development in rat soleus muscle after
exposure to Botulinum Neurotoxin A
Sofie Gjessing, Ole Rahbek, Juan Manuel Shiguetomi, Ole B. Nielsen,
Bjarne Møller-Madsen
Dept. of Children’s Orthopaedics, Aarhus University Hospital; Department of
Biomedicine, Aarhus University
Background:
A fast force development at the beginning of a muscle contrac-
tion is an important functional aspect of locomotion such as gait. In both hu-
man and rat motor function this can be achieved by firing double pulses (dou-
blets) with an inter-pulse interval (IPI) as short as 1.6 ms. We hypothesize that
Botulinum Neurotoxin A (BoNT) reduces the ability of the neuromuscular junc-
tion to transmit doublets and therefore also reduces their potentiating effect on
force development.
Purpose / Aim of Study:
We aimed to examine the effect of BoNT on force
potentiation resulting from doublet stimulation in skeletal muscle.
Materials and Methods:
Experiments were performed on isolated soleus
muscle with intact motor nerve from juvenile Wistar rats that had been given
intramuscular injections of BoNT 1-4 days prior to ex vivo examinations of con-
tractile force.
Findings / Results:
BoNT caused a progressive decline in nerve-stimulated te-
tanic force of the muscle preparations. In controls, nerve-stimulated doublets
increased twitch force to ~200% of force of a single pulse when IPI was 2 ms
and 230% for an interval of 4 ms. This potentiation was, however, attenuated
by BoNT in a manner that depended on the reduction in nerve-stimulated force
and the IPI. When tetanic force stimulated via the nerve was reduced to 0-39%
of force produced by direct stimulation of the muscle fibres, force potentiation,
resulting from nerve stimulation by doublets with an IPI of 2 ms, was signifi-
cantly reduced (P<0.01, one-way ANOVA). No significant effects was observed
at an IPI > 4 ms.
Conclusions:
Treatment with BoNT in vivo reduced the ability of the neuro-
muscular junction to transmit high-frequency doublets in skeletal muscle. This
indicates that treatment with BoNT may interfere with motor function during
locomotion, which could compromise gait.
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