What is the role of botulinum toxin (BTX) injections in pain management?

Updated: Jun 19, 2018
  • Author: Anthony H Wheeler, MD; Chief Editor: Meda Raghavendra (Raghu), MD  more...
  • Print
Answer

Answer

Botulinum toxin (BTX) is a potent neurotoxin produced by the gram-positive, spore-forming, anaerobic bacterium Clostridium botulinum. The 7 immunologically distinct serotypes of BTX are as follows: types A, B, C1, D, E, F, and G. Only types A and B have been developed for commercial use in routine clinical practice. Three type A (BTX-A) preparations have been developed: onabotulinumtoxinA (BOTOX®; Allergan, Inc; Irvine, CA), incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals, LLC; Greensboro, NC) and abobotulinumtoxinA (Dysport; Medicis Pharmaceutical Inc; Scottsdale, AZ). Type B is currently commercially available as Myobloc in the United States.

Each of these neurotoxins are proteins and vary with respect to molecular weight, mechanism of action, duration of effect, and adverse effects. Each toxin is initially synthesized by the bacteria as a single chain polypeptide. Bacterial proteases then "nick" both type A and type B proteins, resulting in a dichain structure consisting of 1 heavy and 1 light chain. Type A is nicked more than type B, and the homology between the toxins is less than 50%. [25]

The mechanism by which acetylcholine release is blocked by BTX is presently better understood than other antinociceptive mechanisms by which these neurotoxins exert their analgesic effects. The toxin first binds to a receptor on the motor nerve terminal at the neuromuscular junction. Each BTX serotype specifically and irreversibly binds to its own receptor, and each neither binds to nor inhibits the other serotypes' receptors. [26, 27]

The binding domain of the toxin appears to be the heavy chain. BTX is then internalized by acceptor-mediated endocytosis into the cholinergic synaptic terminal. After the toxin is bound, an endosome is formed that carries the toxin into the axon terminal. The final step involves cleavage of one of the known synaptic proteins that are required for acetylcholine to be released by the axon. BTXs A, E, and C cleave synaptosome-associated protein-25 (SNAP-25). BTXs B, D, F, and G cleave synaptobrevin, also known as vesicle-associated membrane protein. BTX type C also cleaves syntaxin. [25] The specific manner in which each toxin type may cleave the synaptic protein as well the specific differences in effect on inhibiting acetylcholine release is beyond the scope of this clinical summary. How these differences translate into various observed beneficial and adverse effects is unclear.


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!