Botulinum neurotoxin injections provided a new, localized method to significantly relieve symptoms of chronic pain for many people. Botulinum neurotoxin, a biological product, is injected into specific muscles where it acts to relax the muscles and reduce excessive muscle contractions.
Botulinum neurotoxin is derived from the bacterium Clostridium botulinum. It is a nerve “blocker” that binds to the nerves that lead to the muscle and prevents the release of acetylcholine, a neurotransmitter that activates muscle contractions. If the message is blocked, muscle spasms are significantly reduced or eliminated.
Types of Botulinum neurotoxin
Two forms of botulinum neurotoxin are available for patients. These are:
- · Botulinum neurotoxin type A (trade names Botox, Dysport, and Xeomin)
- · Botulinum neurotoxin type B (trade names Myobloc and Neurobloc).
Other ‘stereotypes of botulinum neurotoxin are under investigation as potential therapeutic agents. These include (in addition to types A and B) types C, D, E, F, and G. Each one has different properties and actions.
No studies have been done to examine the effects of botulinum neurotoxin during pregnancy. It is generally recommended that women not receive botulinum neurotoxin injections while pregnant.
Structure of Botulinum toxin
The BoNT molecule is synthesized as a single chain (150 kD) and then cleaved to form the dichain molecule with a disulfide bridge. The light chain (~50 kD – amino acids 1-448) acts as a zinc (Zn2+) endopeptidase similar to tetanus toxin with proteolytic activity located at the N-terminal end .
The heavy chain (~100 kD – amino acids 449-1280) provides cholinergic specificity and is responsible for binding the toxin to presynaptic receptors; it also promotes light-chain translocation across the endosomal membrane.
Mechanism
· Botulinum toxin is a “blocking agent” preventing the release of certain neurotransmitters, specifically Acetylcholine, from the endings of the motor nerves.
· Botulinum toxin has a light chain and a heavy chain, each of which contributes to the toxicity. The heavy chain allows the protein to bind to and enter a neuron. After the heavy chain allows entry, the light chain acts like a protease and cleaves proteins that would normally allow neurotransmitters to leave the cell.
This is essentially a disruption of exocytosis or the release of neurotransmitters. The blocked neurotransmitters, Acetylcholine, normally transmits a nerve impulse to a muscle, signaling the muscle to contract. By blocking this neurotransmitters, botulinum toxin causes its characteristic flaccid paralysis.
Therapeutic Uses
- Neurological Disorders
- Cervical dystonia: The commonest form of focal dystonia, is characterised by involuntary contractions of cervical muscles, resulting in abnormal head postures and movements, and is often associated with pain . The FDA approved the use of botulinum toxin A for cervical dystonia in 2000 and it is the first-line treatment for this condition.
- Blepharospasm: It is characterised by excessive involuntary contractions of the muscles surrounding the eyes, has been treated with botulinum toxin for years. Injections are applied to the overactive orbicularis oculi muscles.
- Oromandibular dystonia:refers to contractions of the masticatory, facial, and lingual muscles, causing repetitive and sometimes sustained jaw opening, closure or deviation in isolation or in any combination of these. OMD treated with botulinum toxin A, it was found that jaw closing dystonia responds better and treatment was safe and effective .
- Other forms of dystonia: Botulinum toxin is also an effective treatment for spasmodic dysphonia and limb dystonia.
- Hemifacial :Hemifacial spasm is usually caused by an aberrant artery abutting the facial nerve. Micro vascular surgery, which can result in complete resolution of symptoms, is restricted by potential complications associated with surgery. Symptomatic treatment with botulinum toxin is therefore first-line for this condition.
- Spasticity: Spasticity can result from various etiologies including spinal cord injury, stroke, multiple sclerosis (MS) and cerebral palsy. There are botulinum toxin for the treatment of spasticity, and also for the use of different forms of botulinum toxin
- Chronic Migraine: a highly disabling disorder, The benefits of botulinum toxin in migraine initially surfaced when patients were treated cosmetically for wrinkles.
- Disorders of Secretion
- Hyperhidrosis: Primary hyperhidrosis is characterised by excessive and uncontrollable sweating. It affects predominantly the axillae, palms, soles of the feet and face causing considerable social problems. Systemic medications have limited efficacy.
- Sialorrhea: Sialorrhea or drooling occurs when there is excessive saliva in the mouth. This can be seen as an isolated disorder or as part of other neurological disorders such as cerebral palsy, ALS and Parkinson’s disease. botulinum toxin B, found a subjective improvement
- Disorders of the Pelvic Floor
- Neurogenic detrusor overactivity: One of the most common applications of botulinum toxin in urological disorders is for the treatment of detrusor overactivity, which is characterised by urinary frequency and urge incontinence. Evidence from class I trials suggest that botulinum toxin A is effective for neurogenic detrusor overactivity.
- Idiopathic detrusor overactivity: Use of botulinum toxin in the management of idiopathic detrusor overactivity (overactive bladder).
Other off-labelled uses of botulinum toxin in lower urinary tract disorders include detrusor sphincter dyssynergia and painful bladder syndrome. However, the evidence for these indications is lacking and further trials are required.
- Opthalmological Disorders
- Strabismus: Botulinum toxin injection are used in stabismus.
- Dry eye disease: There is also some evidence that botulinum toxin is useful in dysthyroid upper eyelid retraction, entropion, corneal protection secondary to facial paralysis and the control of synkinetic eyelid movements
- Gastrointestinal Disorders
- Achalasia :Achalasia is a disorder of motility characterised by impaired peristalsis and the failure of the lower oesophageal sphincter (LOS) to relax The management of achalasia rely mainly on surgical myotomy, intrasphincteric botulinum toxin injection and pneumatic balloon dilatation. Other off-labelled uses of botulinum toxin in gastrointestinal disorders include anal fissures, gastroperesis and sphincter of Oddi dysfunction.
CONCLUSION:
Considering their influence in the world Botulinum toxin market on the basis of commercial availability and brand identity, companies such as Merz Pharma GmbH and Co. KgaA, Ipsen Group, Allergan, Inc., US Worldmeds, LLC, and Medytox, Inc. are predicted to top the list of best global players. These players are foreseen to take advantage of the colossal adoption of Botulinum toxin on account of tangible benefits such as speedy healing of wounds, shorter stay in the hospital, and small incision.
Leave a Reply