Botulinum Toxin: Definition, Pain Management, When to Consider and Adverse Effects

This type of bacteria is found in the soil and marine sediments; the spores can be detected in fruits, vegetables, and seafood.

Botulinum toxin is the product of Clostridium botulinum. C botulinum bacteria and their spores are ubiquitous.

The growing bacteria produce the botulinum toxin neurotoxin, often referred to as the most poisonous substance known to humanity. The neurotoxin inhibits the release of acetylcholine and produces flaccid paralysis of the affected muscles.

There are seven serologically different types of botulinum toxin: A, B, C1, D, E, F, and G.

The different types of botulinum toxin have different molecular sizes, degrees of activation, and mechanisms of action. Various commercial preparations have other characteristics concerning their clinical performance.

Significant research is being done to study the molecular causes of these differences.

Botulinum toxin in pain management

The diagnosis and treatment of painful muscular syndromes can be frustrating and challenging for any doctor. Typically, therapy for such conditions is therapeutic exercise, analgesics, and a tincture of time.

 

Unfortunately, not all patients respond to this paradigm, and despite heroic efforts by the treating physician, some conditions are refractory to this approach.

Reports have described the alleged effectiveness of using a biological neuromuscular blocking agent, botulinum toxin, in the treatment of painful conditions associated with skeletal muscle.

Although incompletely understood and sometimes controversial, the use of botulinum toxin in the treatment of conditions associated with involuntary muscle contraction, such as focal dystonia and spasticity, is supported by prospective randomized clinical research.

However, while the volume of comparable studies in pain syndromes is growing, the number of randomized clinical trials is limited. In addition, not all of these reports have demonstrated an apparent efficacy of the use of botulinum toxin in all circumstances.

Therefore, given our current understanding of the nature of pain induced by muscle and the lack of future research concerning neuromuscular block and the inhibition of nociception in such conditions.

The anatomical drawings for the location of the injection and the dosing information are intended only as general guidelines; Botulinum toxin therapy should always be individualized, taking into account the patient’s needs and the doctor’s experience.

In addition, the information presented should be used as a convenient reference source, not as a substitute for clinical training in the use of botulinum toxin.

The success of botulinum toxin in pain treatment was initially attributed to its ability to block the release of acetylcholine at the synapse.

An essential feature of botulinum toxin in the treatment of pain is that it is thought that the neurotoxin acts only on the motor nerve endings and avoids sensory nerve fibers for their effects.

Subsequently, however, the effects of botulinum toxin on nociceptive neurons were demonstrated in preclinical studies.

Therefore, analgesic effects are likely to occur, but not as a consequence of a blockage of afferent sensory fibers at the injection site.

Instead, they have been attributed to side effects that may result from muscle paralysis, improved blood flow, the release of nerve fibers under compression by abnormal muscle contraction, and, perhaps more importantly, the effects of the toxin on nociceptive neurons.

Use of Botulinum Toxin in painful neuromuscular disorders

Previous studies of conditions with involuntary muscle contractions have provided some indirect evidence of the analgesic effects of botulinum toxin.

A summary of a Medline search of clinical studies with the titles “botulinum toxin” and “pain” conducted between 1966 and September 2005 resulted in more than 40 studies that included “pain” within the title or summary of the article.

In the report, the pain response with botulinum toxin treatment was cited in the context of treatment for several conditions, including

Tennis elbow, chronic anal fissure, pain attributed to mastectomy and haemorrhoidectomy, headaches (including migraine ), piriformis syndrome, facial pain, myofascial pain, temporomandibular joint syndrome (TMJ, for its acronym in English), pain in lumbar, chronic prostatic pain and whiplash.

The variables in these studies included dose, concentration, injection techniques, concurrent therapeutic modalities, variable diagnoses, and chronicity of neurological dysfunction.

Some patients treated for disorders that included involuntary muscle contraction, such as dystonia, also reported benefits in reducing pain in muscles injected with botulinum toxin.

Evidence indicates that botulinum toxin may be helpful in the treatment of low back pain but that it is probably not effective against episodic migraine and chronic tension headache.

The available evidence was not strong or consistent enough to determine the usefulness of botulinum toxin in treating chronic daily headaches (mainly transformed migraine).

However, the researchers found that patients who received injections of Botulinum Toxin experienced a significant reduction in the duration of their headaches.

One study reported that the use of botulinum toxin to treat painful skin leiomyomas was associated with a better quality of life and a tendency towards better pain at rest.

Botulinum toxin and myofascial pain

Many therapies are available for patients with myofascial pain syndrome.

Much of the variation in the forms of treatment (and diagnosis) of this disorder is likely to result from differences in culture, training, and recognition of an often undiagnosed syndrome of pain, dysfunction, and autonomic dysregulation.

Myofascial pain syndrome associated with trigger points is not fully understood.

Some doctors believe it is due to an acute episode of muscle overload or chronic and repetitive muscle overload.

Myofascial active detonator points (or MTrP) cause pain, exhibit a marked localized sensitivity, often report pain to distant sites, and alter motor function. In addition, MTrP can produce autonomous changes.

For the clinical identification of MTrP, the clinician palpates a sensitive spot located in a nodular portion of a band of tense muscle fibers.

Pressure on a trigger point causes pain in that area and may also cause pain at a site distant from the point below the fingertip (in a phenomenon known as referred pain).

Upon palpation, MTrP also causes pain that reflects the patient’s experience. The insertion of a needle, abrupt palpation, or even an energetic blow with the fingertip directly on the trigger point can result in a brief muscle contraction that the examiner can detect.

This rapid contraction of the muscle fibers of the taut band as a tie is called the local contraction response.

The response is easily seen in muscles that move a relatively small mass or are extensive and superficial (e.g., toe extensors, gluteus maximus). It can cause the limb to jump when the examiner inserts a needle into the point detonator.

The localized abnormal response of the autonomic nervous system can cause piloerection, localized sweating, or regional changes in skin temperature attributed to altered blood flow.

In some small prospective studies, muscle injection with botulinum toxin has been reported to be effective for myofascial pain caused by trigger points (TrPs). However, there is a lack of robust evidence of efficacy in more extensive multicentre trials.

When to consider botulinum toxin

The indications for treatment with botulinum are not entirely clear for patients with myofascial pain syndrome.

These patients may be considered candidates for botulinum toxin if they have not responded to traditional forms of treatment.

They have had a chronic refractory problem for three months or more, have had a complete medical examination to rule out other non-muscle causes for their pain, and have clearly defined TrPs.

The clinician should proceed with caution before considering the use of botulinum toxin to treat a patient with myofascial pain.

Factors that can identify a myofascial pain syndrome as a response potentially favorable to botulinum toxin injections include:

  • Muscle hypertrophy.
  • Neurogenic and vascular compression.
  • The anatomic location isolates the target muscle from other structures.

One of those conditions that meet these criteria is called piriformis muscle syndrome.

Adverse events

Adverse events due to the therapeutic and cosmetic injection of Botulinum toxin include respiratory problems, dysphagia, seizures, flu syndrome, facial and other muscle weakness, blepharoptosis, and skin reactions at the injection site.

The majority of adverse effects are related to local tissue diffusion of Botulinum Toxin. Careful attention to dose, dilution, handling, storage, and injection site is required for optimal treatment outcome and to minimize adverse effects.