Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor

Modugno, Nicola; Priori, Alberto; Berardelli, Alfredo; Vacca, Laura; Mercuri, B.; Manfredi, M.

doi:10.1002/(sici)1097-4598(199812)21:12<1701::aid-mus12>3.0.co;2-k

Cited by 55 publications

(36 citation statements)

References 25 publications

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“…We confirmed the effect of botulinum toxin on the second phase of reciprocal inhibition in a subsequent study in patients with essential tremor. 9 Again, the abnormal reciprocal inhibition could be normalized. These two studies suggest that botulinum toxin injected in the forearm muscles alters the excitability of spinal cord circuitry.…”

Section: Discussionsupporting

confidence: 89%

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

et al. 2000

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To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure‐of‐eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50–100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms. Ann Neurol 2000;48:20–26

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Section: Discussionsupporting

confidence: 89%

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

et al. 2000

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“…[47][48][49] During the initial weeks after injection, muscles treated with BTX-A show some variability in the size of muscle fibers, and demonstrate intra-cellular changes consistent with denervation (i.e. central mitochondria dispersed toward the periphery).…”

Section: Action On Striated Versus Smooth Musclementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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“…In patients with upper limb dystonia BT can normalise altered reciprocal inhibition between flexor and extensor muscles 2 2 . A similar effect was also demonstrated in patients with essential tremor 23 . EMG changes of the contralateral ocular muscles after injection of BT into the lateral rectus muscle also s u ggest central effects 24 .…”

Section: Botulinum Toxin Action On the Central Nervous System (Cns)mentioning

confidence: 99%

Botulinum toxin: mechanisms of action

Dressler

Saberi²,

Barbosa³

2005

Arq. Neuro-Psiquiatr.

244

100

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-This review describes therapeutically relevant mechanisms of action of botulinum toxin (BT). B T 's molecular mode of action includes extracellular binding to glycoproteine structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the bloodbrain-barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated through blockade of substance P, glutamate and calcitonin gene related peptide.KEY WORDS: botulinum toxin, mechanisms of action, acetylcholine, muscle spindles, stretch reflex, smooth muscles, exocrine glands, retrograde axonal transport, blood-brain-barrier, substance P.Toxina botulínica: mecanismos de ação RESUMO -O propósito deste artigo é uma revisão dos mecanismos de ação da toxina botulínica (TB) relevantes para a compreensão do seu uso terapêutico. A ação da TB a nível molecular consiste na sua ligação extracelular a estruturas glicoprotéicas em terminais nervosos colinérgicos e no bloqueio intracelular da secreção de acetilcolina. A TB interfere no reflexo espinal de estiramento através do bloqueio de fibras musculares intrafusais causando redução da sinalização aferente veiculada por fibras Ia e II e do tono muscular. Portanto, o efeito da TB pode estar relacionado não somente à paresia muscular mas também à inibição reflexa espinal. A TB promove ainda o bloqueio de fibras autonômicas para músculos lisos e glândulas exócrinas. Apesar de ocorrer alguma difusão sistêmica após a aplicação intramuscular a TB não atinge o sistema nervoso central (SNC) devido ao seu peso molecular (não atravessa a barreira hematoencefálica) e à lentidão do seu transporte axonal retrógrado que permite a sua inativação. Os efeitos indiretos sobre o SNC são: inibição reflexa, reversão das alterações da inibição recíproca, da inibição intracortical e de potenciais evocados somatosensoriais. A redução da dor induzida por formalina sugere que a TB tenha efeito analgésico direto possivelmente mediado por bloqueio da substância P, do glutamato e do peptídeo relacionado ao gene da calcitonina.PA L AV R A S -C H AVE: toxina botulínica, mecanismos de ação, acetilcolina, fusos musculares; reflexo de estiramento, músculos lisos, glândulas exócrinas, transporte axonal retrógrado, barreira hematoencefálica, substância P.

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Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor

Cited by 55 publications

References 25 publications

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Botulinum toxin: mechanisms of action

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