Botulinum toxin is the most lethal substance known to humankind being 100 billion times more toxic than cyanide. It was first discovered by German physician and poet Justinus Kerner during an outbreak of botulinum in Germany due to spoiled sausages. He went on to conduct clinical experiments on himself to develop treatment and preventative measures.
The first medical use of the toxin was for the treatment of strabismus by Alan Scott in 1980. Since that time, Botulinum toxin type A is now one of the most widely used and versatile drugs in medicine, with new applications being discovered and developed.
Botulinum toxin offers a viable alternative for various types of pain management compared with existing treatments. Its analgesic effect was first noted in human studies of torticollis, where 60-80% of patients reported significant
pain relief.
As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines. However, the body of evidence for use in other chronic pain conditions is growing. Research has been particularly focused on syndromes such as myofascial pelvic pain, neuropathic pain and regional pain in the shoulder, knees or back.
Mechanism of action
In the active state, botulinum toxin consists of a polypeptide chain with both a heavy and light chain bound by disulphide bonds. The heavy chain binds irreversibly to presynaptic cholinergic receptors at the neuromuscular junction of motor neurons, autonomic ganglia and post-ganglionic sympathetic and parasympathetic neurons.
Botulinum toxin can reduce or alleviate chronic pain through several possible mechanisms:
- Reduction in muscle spasms and overactivity through blockade of acetylcholine release from presynaptic vesicles.
- Reduction in neurogenic inflammation and pain. Diminishes release of neurotransmitters and peptides important in pain transmission including substance P, calcitonin gene-related peptide and bradykinin.
- Reduction in sympathetically mediated pain through reduction in sympathetic neuron discharge
- Reduced resting discharge of muscle spindles that contributes to reduced central sensitisation and alpha motor neuron activity.
- Modulation of brain stem sensory neurons.
Role in pain management
Botulinum toxin is a novel agent and has a unique role in multidisciplinary pain management. It is an attractive option for patients who have failed conservative therapies and do not want many of the cognitive and addictive side effects associated with pain medications. Due to its differing mechanisms of action, it can be used in patients in whom more traditional pain treatments are not indicated or who have had a poor response to corticosteroid or radiofrequency ablation treatments.
Botulinum toxin has been shown to help patients with a wide variety of pain conditions. The strongest results so far are seen with neuropathic pain syndromes such as trigeminal neuralgia and peripheral diabetic neuropathies. It should also be considered for patients with musculoskeletal pain syndromes such as chronic lower back pain, neck pain and headaches.
Commonly, the effects of Botulinum toxin last up to three months and, depending on the pain condition, may last longer if combined with physical therapy. Overall, it is a well tolerated treatment but contraindicated in pregnancy, past hypersensitivity and neuromuscular disorders. Other risks to consider are needle site bleeding and infection, muscle weakness and flu-like symptoms.
Clinical interest in Botulinum toxin is growing rapidly. High rates of chronic pain and treatment resistance to available options on a background of the opioid crisis increases the need for innovate treatments. In the coming years we will likely see continued research, clinical education, and recognition of Botulinum toxin in chronic pain treatment guidelines.
Key messages
- Wide range of applications including headaches, nerve pain, neck and back pain
- Analgesic effects beyond muscle relaxation properties
- Patients who have not responded to conservative management or other treatments.
– References available on request
Author competing interests – no relevant disclosures