How Does Botulinum Work?

Mechanism of Botulinum

  • Botulinum toxin has been effectively used in {the} treatment of various spastic disorders such as cervical dystonia, strabismus, blepharospasm and facial nerve disorders. It is important to understand how this lethal toxin has been used to our benefit in providing relief to patients suffering from numerous intractable spastic disorders.

Understanding {the} Basics of Signal Transmission

  • Various electrical signals originate in {the} brain and trickle down various neuronal pathways in {the} spinal cord, through {the} spinal nerves to {the} neuromuscular junction (NMJ) and finally to {the} muscle cells which contract and cause {the} desired action. The chemical messenger that transmits these electrical signals across various nerve cells and neuromuscular junction to {the} muscles is {the} neurotransmitter, Acetylcholine (ACh). The acetylcholine binds to receptors on {the} muscle cells and causes {the} muscle to contract or shorten.
  • Botulinum toxin blocks {the} release of Acetylcholine from {the} nerve terminal at {the} neuromuscular junction thereby preventing muscle contraction. This effect of botulinum causes paralysis or reduces abnormal muscle contraction allowing {the} muscles to become less stiff.

Mechanism of Action of Botulinum Toxin

  • Botulinum Toxin acts by blocking neural transmission at four different sites in {the} body - {the} neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings, all of which release {the} neurotransmitter Acetylcholine. It irreversibly blocks {the} release of acetylcholine, {the} principal neurotransmitter at {the} neuromuscular junction, without causing degeneration of {the} nerve terminals.
  • Hyperactive muscle contraction is caused by excessive release of Acetylcholine at {the} neuromuscular junction in certain disorders. Exaggerated muscle spasms are relieved by botulinum toxin providing reliable relief of symptoms. Botulinum toxin does not however provide a cure for {the} underlying disease process.
  • The botulinum-induced irreversible paralytic effect starts in 24 to 72 hours and is complete in four to seven days after injection. There is recovery of muscle function only with {the} formation of new nerve terminals and new synaptic contacts which takes about two to three months.

Neuromuscular blockage by botulinum is a three-step process. The following is a step-wise description of how botulinum toxin blocks transmission at {the} neuromuscular junction:

  • Binding of Botulinum toxin to {the} nerve terminal: Once injected, {the} toxin rapidly and firmly binds at receptor sites on cholinergic nerve terminals in a saturable fashion. The binding domain of {the} Botulinum toxin type A appears to be {the} heavy chain, which is selective for cholinergic nerve terminals.
  • Internalization of Botulinum toxin: The toxin is internalized via receptor-mediated endocytosis through {the} synaptic recycling process. The plasma membrane of {the} nerve cell invaginates around {the} toxin-receptor complex, forming a toxin-containing vesicle inside {the} nerve terminal. After internalization, {the} light chain of {the} toxin molecule, which has been demonstrated to contain {the} transmission-blocking domain is released into {the} cytoplasm of {the} nerve terminal.
  • Blocking of Acetylcholine Release into {the} NMJ: Botulinum toxin attaches to {the} Acetylcholine-containing vesicles in {the} nerve terminal cleaving SNAP-25, a cytoplasmic protein that is located on {the} cell membrane and required for release of Acetylcholine. The affected nerve terminals do not release Acetylcholine into {the} NMJ and thus prevents contraction of {the} muscle.

Why do you have to repeat Botulinum Injections?

  • Nerve Sprouting is an interesting phenomenon in which new nerve terminals sprout parallel to {the} one blocked by botulinum and establishes new neuromuscular junctions. This results in a gradual functional recovery of {the} neuromuscular junction. Newer research suggests that {the} nerve sprouts retract as {the} original nerve terminal regains its function over time. This functional recovery takes about 2 to 3 months.
  • The phenomenon of Nerve Sprouting is important because once functional recovery is complete, repeat injections should be given to maintain {the} desired clinical effect.
  • Hence, repeat injections should be given every three or four months based on individual response to therapy. It should be kept in mind that tolerance to {the} drug develops with repeated injections due to antibody formation. Therefore, it is advised that {the} lowest effective dose be given as infrequently as possible.
  • Normally your brain sends electrical messages to your muscles so that they can contract and move. The electrical message is transmitted to {the} muscle by a substance called acetylcholine.
  • Botulinum works to block {the} release of acetylcholine and, as a result, {the} muscle doesn't receive {the} message to contract.

 

 

What Characterizes hyperactive muscle contraction?

  • At a normal neuromuscular junction, a nerve impulse triggers {the} release of acetylcholine, which causes {the} muscle to contract. Hyperactive muscle contraction, regardless of {the} underlying cause, is characterized by excessive release of acetylcholine at {the} neuromuscular junction.

 

Binding

  • Botulinum Toxin Type A binds to {the} motor nerve terminal. The binding domain of {the} type A molecule appears to be {the} heavy chain, which is selective for cholinergic nerve terminals

Internalization

  • Botulinum toxin type A is internalized via receptor-mediated endocytosis, a process in which {the} plasma membrane of {the} nerve cell invaginates around {the} toxin-receptor complex, forming a toxin-containing vesicle inside {the} nerve terminal.
  • After internalization, {the} light chain of {the} toxin molecule, which has been demonstrated to contain {the} transmission-blocking domain,5 is released into {the} cytoplasm of {the} nerve terminal.

 

 Blocking

  • Botulinum toxin type A blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on {the} cell membrane and that is required for {the} release of this transmitter.
  • The affected terminals are inhibited from stim

    How Does Botulinum Work?

    Mechanism of Botulinum

    • Botulinum toxin has been effectively used in {the} treatment of various spastic disorders such as cervical dystonia, strabismus, blepharospasm and facial nerve disorders. It is important to understand how this lethal toxin has been used to our benefit in providing relief to patients suffering from numerous intractable spastic disorders.

    Understanding {the} Basics of Signal Transmission

    • Various electrical signals originate in {the} brain and trickle down various neuronal pathways in {the} spinal cord, through {the} spinal nerves to {the} neuromuscular junction (NMJ) and finally to {the} muscle cells which contract and cause {the} desired action. The chemical messenger that transmits these electrical signals across various nerve cells and neuromuscular junction to {the} muscles is {the} neurotransmitter, Acetylcholine (ACh). The acetylcholine binds to receptors on {the} muscle cells and causes {the} muscle to contract or shorten.
    • Botulinum toxin blocks {the} release of Acetylcholine from {the} nerve terminal at {the} neuromuscular junction thereby preventing muscle contraction. This effect of botulinum causes paralysis or reduces abnormal muscle contraction allowing {the} muscles to become less stiff.

    Mechanism of Action of Botulinum Toxin

    • Botulinum Toxin acts by blocking neural transmission at four different sites in {the} body - {the} neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings, all of which release {the} neurotransmitter Acetylcholine. It irreversibly blocks {the} release of acetylcholine, {the} principal neurotransmitter at {the} neuromuscular junction, without causing degeneration of {the} nerve terminals.
    • Hyperactive muscle contraction is caused by excessive release of Acetylcholine at {the} neuromuscular junction in certain disorders. Exaggerated muscle spasms are relieved by botulinum toxin providing reliable relief of symptoms. Botulinum toxin does not however provide a cure for {the} underlying disease process.
    • The botulinum-induced irreversible paralytic effect starts in 24 to 72 hours and is complete in four to seven days after injection. There is recovery of muscle function only with {the} formation of new nerve terminals and new synaptic contacts which takes about two to three months.

    Neuromuscular blockage by botulinum is a three-step process. The following is a step-wise description of how botulinum toxin blocks transmission at {the} neuromuscular junction:

    • Binding of Botulinum toxin to {the} nerve terminal: Once injected, {the} toxin rapidly and firmly binds at receptor sites on cholinergic nerve terminals in a saturable fashion. The binding domain of {the} Botulinum toxin type A appears to be {the} heavy chain, which is selective for cholinergic nerve terminals.
    • Internalization of Botulinum toxin: The toxin is internalized via receptor-mediated endocytosis through {the} synaptic recycling process. The plasma membrane of {the} nerve cell invaginates around {the} toxin-receptor complex, forming a toxin-containing vesicle inside {the} nerve terminal. After internalization, {the} light chain of {the} toxin molecule, which has been demonstrated to contain {the} transmission-blocking domain is released into {the} cytoplasm of {the} nerve terminal.
    • Blocking of Acetylcholine Release into {the} NMJ: Botulinum toxin attaches to {the} Acetylcholine-containing vesicles in {the} nerve terminal cleaving SNAP-25, a cytoplasmic protein that is located on {the} cell membrane and required for release of Acetylcholine. The affected nerve terminals do not release Acetylcholine into {the} NMJ and thus prevents contraction of {the} muscle.

    Why do you have to repeat Botulinum Injections?

    • Nerve Sprouting is an interesting phenomenon in which new nerve terminals sprout parallel to {the} one blocked by botulinum and establishes new neuromuscular junctions. This results in a gradual functional recovery of {the} neuromuscular junction. Newer research suggests that {the} nerve sprouts retract as {the} original nerve terminal regains its function over time. This functional recovery takes about 2 to 3 months.
    • The phenomenon of Nerve Sprouting is important because once functional recovery is complete, repeat injections should be given to maintain {the} desired clinical effect.
    • Hence, repeat injections should be given every three or four months based on individual response to therapy. It should be kept in mind that tolerance to {the} drug develops with repeated injections due to antibody formation. Therefore, it is advised that {the} lowest effective dose be given as infrequently as possible.
    • Normally your brain sends electrical messages to your muscles so that they can contract and move. The electrical message is transmitted to {the} muscle by a substance called acetylcholine.
    • Botulinum works to block {the} release of acetylcholine and, as a result, {the} muscle doesn't receive {the} message to contract.

     

     

    What Characterizes hyperactive muscle contraction?

    • At a normal neuromuscular junction, a nerve impulse triggers {the} release of acetylcholine, which causes {the} muscle to contract. Hyperactive muscle contraction, regardless of {the} underlying cause, is characterized by excessive release of acetylcholine at {the} neuromuscular junction.

     

    Binding

    • Botulinum Toxin Type A binds to {the} motor nerve terminal. The binding domain of {the} type A molecule appears to be {the} heavy chain, which is selective for cholinergic nerve terminals

    Internalization

    • Botulinum toxin type A is internalized via receptor-mediated endocytosis, a process in which {the} plasma membrane of {the} nerve cell invaginates around {the} toxin-receptor complex, forming a toxin-containing vesicle inside {the} nerve terminal.
    • After internalization, {the} light chain of {the} toxin molecule, which has been demonstrated to contain {the} transmission-blocking domain,5 is released into {the} cytoplasm of {the} nerve terminal.

     

     Blocking

    • Botulinum toxin type A blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on {the} cell membrane and that is required for {the} release of this transmitter.
    • The affected terminals are inhibited from stimulating muscle contraction.
    • The toxin does not affect {the} synthesis or storage of acetylcholine or {the} conduction of electrical signals along {the} nerve fiber.

    Nerve Sprouting

    • A nerve sprout eventually establishes a new neuromuscular junction, and muscle activity gradually returns.
    • However, new research suggests that this new nerve sprout retracts and {the} original junction returns to functionality.

    Eventually, {the} new nerve sprouts retract and {the} original nerve ending regains its function.

    In either case, repeat injections of Botulinum Purified Neurotoxin Complex may possibly be required to maintain {the} desired clinical effect.

     

    • The use of Botulinum can be effective in reducing this excessive activity.

    • Botulinum is indicated fo r {the} treatment of cervical dystonia in adults to decrease {the} severity of abnormal head position and neck pain associated with cervical  
      dystonia.

    • Botulinum is indicated for {the} treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above.

    • Botulinum blocks neuromuscular transmission through a three-step process. This is believed to be followed by {the} sprouting of new axon terminals, which results in {the} reestablishment of neuromuscular transmission.1
Procedures
Copyright © 1997-2017 EyePlastics.com. All rights reserved.