Tetanus toxin reduces local and descending regulation of the H-reflex

Abstract

Introduction Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response. Methods H-reflexes were obtained from the tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles in rats 7 days after intramuscular injection of tetanus toxin into the TA. Results We found effects of the toxin on the threshold, amplitude, and duration of H-waves from the TA. The toxin inhibited rate-dependent depression in the FDB between the stimulation frequencies of 0.5–50 HZ and when a conditioning magnetic stimulus applied to the brain preceded a test electrical stimulus delivered to the plantar nerve. Conclusions Tetanus toxin increased the amplitude of the H-wave and reduced the normal depression of H-wave amplitude that is associated with closely timed stimuli, two phenomena that could contribute to hyperactivity of the stretch reflex.

Evidence for central antispastic effect of botulinum toxin type A

“…injection into the rat gastrocnemius. TeNT, unlike BoNT/A and other BoNT serotypes, induces muscular spasm following its axonal transport and transcytosis into ventral horn inhibitory synapses which control the motor neuron activity (Brooks, Curtis, & Eccles, ; Matthews et al, ; Restani et al, ). Although the muscular hyperactivity in hyperkinetic movement disorders and spasticity is etiologically different, it is similarly associated with impaired inhibitory control of lower motor neurons (Hallett, ; Kita & Goodkin, ).…”

“…By employing 0-to 50-μl luer tip Hamilton syringe coupled to 0.45 mm × 16 mm disposable needles, rats were percutaneously injected with 20 μl of neurotoxin divided into two injection sites (10 μl each site) into lateral and medial bellies of the right gastrocnemius. The doses of TeNT (1.5 ng) or BoNT/A (5 U•kg −1 ) were chosen based on previously used non-systemic doses (Cui, Khanijou, Rubino, & Aoki, 2004;Matak et al, 2012;Matthews et al, 2014) and preliminary experiments.…”

“…Muscle hypertonia and hyperkinesia in dystonia and spasticity involves impaired balance between excitatory and inhibitory inputs to α-motor neurons, and the pharmacological treatment aimed at controlling the excitatory drive or increasing the inhibitory transmission at the spinal cord level reduces their symptoms (Hallett, 2011;Kita & Goodkin, 2000). Tetanus toxin (TeNT), a homologue of the BoNTs, exerts spastic paralysis by blocking the synaptic inhibitory input to αmotor neurons (Matthews, Fishman, & Wittenberg, 2014;Restani et al, 2012). Quantification of local spastic paralysis induced by low doses of TeNT, given i.m., might be used to study the effects of antispastic drugs (Kutschenko et al, 2012), although this possibility has not been examined so far.…”