Can Botulinum Toxin Be Used for Pain Relief?

Botulinum toxin is one of the most toxic biological substances found on earth, produced by anaerobic bacteria known as Clostridium botulinum. Botulinum toxin is a neurotoxin excreted by C. botulinum when the bacterial spores find the right environment to germinate and multiply, for instance, in the human gut where it may cause botulism, a serious type of food poisoning.

Botulinum toxin binds to nerve terminals in muscles and prevents the release of acetylcholine. Acetylcholine is the principal neurotransmitter in neuromuscular junctions, which activate muscles. The blockage of acetylcholine stops the transmission of nerve signals and paralyzes the muscles.

There are seven identified types of botulinum toxin, named A to G, with two sub-types in C. Currently, botulinum toxin type A is being studied for use in pain management. Some investigators suggest an eighth type but others claim it is a combination of parts of types A and F.

Botulinum toxin is referred to as a miracle poison because its pharmacologic properties can be put to therapeutic use with minute and carefully administered doses. Botulinum toxin is purified and diluted with human serum albumin before use on people.

Botulinum toxins are commonly administered to smooth out facial wrinkles from aging, such as frown lines (glabellar lines) and crow’s feet (canthal lines). Botulinum toxin injections provide temporary relief by relaxing stiff or hyperactive muscles in certain conditions such as

• Cervical dystonia (abnormal neck muscle contraction)
• Blepharospasm (involuntary eye twitching)
• Strabismus (crossed eyes)
• Limb spasticity (limb muscle stiffness)
• Neurogenic bladder (loss of bladder control)
• Migraine headache
• Axillary hyperhidrosis (excessive armpit sweating)
• Sialorrhea (drooling caused by cerebral palsy)

The mainstay of pain management therapy for chronic pain conditions is rest, physical therapy and painkillers. Researchers are increasingly investigating the use of botulinum toxin for pain relief (analgesia), with fewer side effects than conventional painkillers.

The exact mechanism of botulinum toxin’s analgesic effects is not fully understood. Some amount of indirect pain relief may be from the relaxation of taut muscles which can improve blood supply and release compressed nerves.

Ongoing studies show that botulinum toxin also blocks certain pain transmitting neurotransmitters such as glutamate and substance P, reducing the intensity and duration of pain. Further studies are required to establish the direct and/or indirect analgesic effects of botulinum toxin.

Several studies have found botulinum toxin to be effective for temporary pain relief from painful neuromuscular conditions. People treated with botulinum toxin for muscle contraction have also reported pain reduction in those muscles. Botulinum toxin A has FDA approval for use in migraine headaches and pain from cervical dystonia.

Botulinum toxin for myofascial pain syndrome (muscle pain) is considered only when a patient does not respond to traditional forms of treatment. Some studies have reported that botulinum toxin has been effective in myofascial pain caused by trigger points.

Clinical trials have indicated that use of botulinum toxin A for pain management is effective in conditions that include:

• Chronic migraine headache
• Cervicogenic headache
• Tension headache
• Medication overuse headache
• Whiplash associated neck pain
• Temporomandibular joint disorder
• Nerve pain such as
  • Trigeminal neuralgia
  • Postherpetic neuralgia
  • Neuropathic pain (pain from nerve damage)
• Chronic lower back pain
• Piriformis muscle syndrome
• Chronic prostatic pain
• Chronic anal fissure
• Myofascial pain syndrome
• Postoperative pain and spasm in cerebral palsy
• Postoperative pain from mastectomy
• Postoperative pain from hemorrhoidectomy
• Tennis elbow (lateral epicondylitis)
• Knee pain
• Shoulder pain

Botulinum toxin therapy is individualized depending on the patient’s needs. Depending on the condition treated, botulinum toxin injection may be administered

• Into the inner layer of the skin (intradermal)
• Into the tissue under the skin (subcutaneous)
• Into the affected muscle (intramuscular)
• Into the bladder for neurogenic bladder
• Into the salivary glands for sialorrhea

For certain muscular injections, the doctor may use electromyography or electrical muscle stimulation for needle guidance. The doctor may also give a muscle relaxant to prevent short-term pain or discomfort from the injection.

Botulinum toxin’s effects on the targeted nerve terminals are irreversible, but new nerve terminals normally sprout within about three months, returning sensation and function to the muscle. . Botulinum toxin injections are usually repeated every three to four months, but the period between injections may increase, because the muscle atrophies to some extent with each injection.

The use of botulinum toxin A for pain relief has FDA approval only for:

• Pain related to cervical dystonia
• Chronic migraines

The FDA-approved botulinum toxin drugs are:

• OnabotulinumtoxinA (Botox, Botox Cosmetic)
  • Botox is approved for
    • Cervical dystonia
    • Axillary hyperhidrosis
    • Strabismus
    • Blepharospasm
    • Neurogenic detrusor hyperactivity
    • Chronic migraine
    • Upper limb spasticity
  • Botox Cosmetic is approved for
    • Glabellar lines
    • Canthal lines
• AbobotulinumA (Dysport)
  • Approved for
    • Upper and lower limb spasticity
    • Cervical dystonia
    • Glabellar lines
    • Lower limb spasticity in children aged 2 years or older
• IncobotulinumtoxinA (Xeomin)
  • Approved for
    • Upper and lower limb spasticity
    • Cervical dystonia
    • Blepharospasm
    • Glabellar lines
    • Chronic sialorrhea
• PrabotulinumtoxinA (Jeuveau)
  • Approved for moderate to severe glabellar lines.
• RimabotulinumtoxinB (Myobloc)
  • Approved for cervical dystonia

Side effects of botulinum toxin are few and usually resolve on their own. Potential side effects when used for pain relief include:

• Injection site reactions such as
  • Pain
  • Redness
  • Bruising
  • Infection
  • Hematoma
• Flu-like symptoms such as
  • Fever
  • Chills
  • Lightheadedness
  • Headache
• Muscle soreness
• Hypertension
• Nausea
• Diarrhea
• Abdominal pain
• Swallowing difficulties (dysphagia)
• Respiratory problems
• Pain or weakness in neighboring muscles
• Neck weakness
• Fatigue and lethargy
• Dizziness
• Dry mouth
• Hoarse voice (dysphonia)