BOTULINUM TOXIN

IN

PAIN MANAGEMENT

 

Morris Jagodowicz, M.D.

 

LEARNING OBJECTIVES:  After reading this article with attached slides, you should:

  1. Have an understanding of what Botulinum Toxin is and it's effect on the nervous system.

  2. Have an understanding of the labeled and off-labeled uses of Botulinum Toxin

  3. Have an understanding of the usual dosage used for the various serotypes of Botulinum Toxin

  4. Have an understanding of how Botulinum Toxin is used to treat patients.

THIS LECTURE IS APPROVED FOR 3 CME, CEU, OR DENTAL CREDITS

 

 

Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium in the shape of a rod.  The clinical syndrome of botulism can occur following ingestion of contaminate food. The bacteria are found in water and soil.  The organism was first studied in the early 19th century by Justinus Kerner.  He studied the effect of sausage poisoning (Botulism) and concluded that this poison may block sympathetic nervous system excitability. The term “botulism” was coined by Muller in 1970. The Latin form is botulus, which means sausage.

 

 

 

 

 

 

Botulinum toxin is broken into 7 neurotoxins (labeled as types A,B,C [C1,C2], D,E,F, and G, which are antigenically and serologically distinct but structurally similar.  Human botulism is mainly due to types A,B,E, and, rarely F. Types C and D cause toxicity only in animals.

The three serotypes most commonly available in the United States and Europe are Botulinum Toxin A (Botox and Ipsen) and Botulinum Toxin B (Myobloc).  Due to the lower PH of the Myobloc (presently manufactured by Solstice Neurosciences), may account for the increase in pain on injection.

 

Botox and Myobloc are both approved in the United States. Dysport is approved in Europe. Above you will note the list of indications for Botulinum Toxin (Botox). At the present time, Myobloc is only approved in the U.S. for cervical dystonia. Dysport is used in the United Kingdom mainly for patients with multiple sclerosis. There are many off-label uses for Botulinum Toxin.

 

Botulinum Toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect.  This mechanism is the foundation for the development of the toxin as a therapeutic tool. Botox and Ipsen cleave synaptosome-associated protein- SNAP-25, a presynaptic membrane protein required for fusion of neurotransmitter-containing vesicles.  Myobloc cleaves a vesicle-associated membrane protein-VAMP, also known as synaptobrevin.

 

The above chart lists the many reported uses of Botulinum Neurotoxins.  Note that more recent studies have shown positive results using Botox for migraine and tension type headaches.  Myofascial pain associated with the Paraspinous muscles and the Piriformis muscles have also shown improvement with the toxin.

 

Focal Dystonias:

 

 

 

 

 

 

 

Botulinum Toxin A and B are both approved in the United States for treatment of Cervical Dystonia.

 

 

 

 

 

 

 

 

 

Botulinum Toxin A and B are the first line therapy for patients with mild, moderate, or severe symptoms.  Oral medications such as anticholinergics and muscle relaxants are used for mild cervical dystonia.  Physical therapy is always used in conjunction with Botulinum Toxin.  Below is the usual dosage for Botox treatment of cervical dystonia.

 

 

Below is the dosage used with Botulinum Toxin B (Myobloc) for cervical dystonia.

 

Below is a list of adverse events reported with the use of Botox in patients with cervical dystonia. Note that dysphagia (difficulty swallowing) is the highest percentage at 18.6. In a Myobloc study of patients previously tolerant to Botox, the incidence of dysphagia was as high as 48%.

 

 

 

 

 

 

What are TMDs?  By definition, tempero-mandibular disorders are a group of pathologic conditions involving the tempero-mandibular joint (TMJ), masticatory muscles, and/or associated structures.  There are three main categories of TMD.

  1. Myofascial pain
  2. Internal derangement of the joint
  3. Degenerative joint disease

 

 

 

 

 

 

 

 

 

 

 

 

Injection along the course of the Piriformis muscle for treatment of Piriformis Syndrome (Sciatic nerve pain secondary tightness of the Piriformis muscle). The usual dosage is about 200 units of Botox or 10,000 units of Myobloc.  Localization of the Piriformis muscle is performed with EMGs or fluoroscopic evaluation of the muscle

 

 

 

Botulinum Toxin A and B have been used to treat Thoracic Outlet Syndrome.  This is an off-label usage of the toxin. The syndrome involves compression or impingement on nerves, artery, or vein.  Neurogenic thoracic outlet syndrome is the most common involving the brachial plexus.  The Anterior Scalene muscle usually is contracted and shortens due to injury or overuse.  This muscle can be injected with either a local anesthetic to test for Thoracic Outlet Syndrome or injected with Botulinum Toxin for a longer lasting effect.

 

 

In summary, there are many uses of Botulinum Toxin in the clinical arena both labeled and off-labeled.  More recent studies are underway for treatment of migraine and tension type headaches, use of Botulinum Toxin in the treatment of chronic pancreatitis and fibromyalgia.  Use of Botulinum Toxin for myofascial pain syndromes is important in treatment of both neck and back pain.

 

 

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