Botulinum toxin type A (BoNT-A, ‘Botox’) is one of the most extensively studied drugs in neurology and pain medicine. At our Centre we use it in accordance with FDA and EAN guidelines for chronic migraine (PREEMPT protocol), bruxism, dystonias, spasticity and selected pain syndromes.

  • Botulinum toxin – 100 units (various indications)
  • Chronic migraine – full PREEMPT protocol 200 units
  • AZALURE 125 units – cosmetic-analgesic facial indications
  • Bruxism – individual dose

Mechanism of Action

Botulinum toxin type A is produced by Clostridium botulinum. The molecule consists of two chains (heavy and light) connected by a disulphide bridge. After intramuscular or subcutaneous administration, the heavy chain binds to receptors on nerve endings, then the light chain enters the neuron and cleaves the SNAP-25 protein, which is critical for fusion of synaptic vesicles with the cell membrane.

The clinical effects of botulinum toxin in pain are multidirectional:

  • BLOCKADE OF ACETYLCHOLINE RELEASE at the neuromuscular junction – muscle paralysis (effect: 3 months)
  • REDUCTION OF PAIN NEUROTRANSMITTER RELEASE (CGRP, substance P, glutamate) at C-fibre endings – the key analgesic mechanism
  • MODULATION OF PAIN RECEPTORS (TRPV1, P2X3) on nociceptors
  • RETROGRADE TRANSPORT of toxin to the brainstem – modulation of central pain pathways
  • REDUCTION OF PERIPHERAL AND CENTRAL SENSITISATION – critical in chronic pain
  • Effect lasts 10–12 weeks, until new nerve endings regenerate

CHRONIC MIGRAINE – PREEMPT Protocol

Botulinum toxin was approved by the FDA for preventive treatment of chronic migraine (≥15 headache days per month, pain lasting ≥4 hours) in 2010, based on the PREEMPT 1 and PREEMPT 2 clinical trials (Phase III REsearch Evaluating Migraine Prophylaxis Therapy). It is currently the only botulinum toxin registered exclusively for chronic migraine prevention.

Standard PREEMPT protocol

155–200 units in 31–39 injection points:

  • FRONTALIS muscle – 20 units at 4 points (5 units per point)
  • GLABELLAR muscles (corrugator + procerus) – 15 units at 3 points
  • TEMPORALIS muscles – 40 units at 8 points (5 units each)
  • OCCIPITALIS muscles – 30 units at 6 points
  • CERVICAL PARASPINAL muscles – 20 units at 4 points
  • TRAPEZIUS muscle – 30 units at 6 points (5 units each)
  • OPTIONAL (‘follow-the-pain’ technique) – additional 40 units in the most painful areas

At our Centre we routinely use the full dose of 200 units (dilution: 100 units in 2 ml saline, 5 units/0.1 ml per point) – the literature indicates that the full dose gives better results than the minimum 155 units, particularly in patients with severe pain and pronounced trigger points.

Efficacy of botulinum toxin in chronic migraine:

  • Reduction in migraine days by 8.4 days/month vs 6.6 days in the placebo group (PREEMPT studies)
  • 47.1% of patients achieve ≥50% reduction in headache days (responder rate)
  • After 12 months, 70% of responders achieve ≥50% reduction
  • After 60 months (5 years), 90% of responders achieve significant reduction
  • Drop from 22.7 headache days/month (baseline) to 5.5 days/month after 5 years of systematic treatment
  • Significant reduction in acute medication use (from 33.4 doses/month to 5.7 doses)
  • Treatment cycle: every 12 weeks (quarterly). Full effect: after 2–3 cycles (6–9 months)

BRUXISM – Excessive Tooth Clenching

Bruxism (conscious or involuntary tooth clenching/grinding) leads to chronic facial and head pain, temporomandibular joint dysfunction, tooth fractures and dental complications. Botulinum toxin injected into the masseter and temporalis muscles effectively reduces clenching force without completely eliminating chewing function.

Standard dose: 25–50 units per masseter muscle (50–100 units total). Effect lasts 4–6 months, can be repeated. Additional cosmetic effect – narrowing of the lower face (reduction of masseter hypertrophy). Efficacy in bruxism-related facial pain: 70–90% of patients experience significant relief.

AZALURE 125 units – Cosmetic-Medical Preparation

AZALURE is an alternative botulinum toxin type A preparation, available at our Centre in 125 unit doses at a competitive price. Used for smaller indications (episodic migraine, tension headaches, partial dystonias, bruxism) and for aesthetic-analgesic facial indications.

Other Pain Indications

  • Cervical dystonia (spastic torticollis)
  • Hemifacial spasm
  • Post-stroke spasticity
  • Refractory occipital neuralgia
  • Painful shoulder syndrome with a muscular component
  • Piriformis syndrome
  • Difficult-to-treat trigger point pain

Procedure Sequence (using the PREEMPT migraine protocol as an example)

  • Qualifying consultation with a headache diary (confirming ≥15 headache days/month, including 8 days meeting migraine criteria).
  • Patient in a sitting or supine position, skin disinfection.
  • Dilution of 100 units of toxin in 2 ml saline (5 units/0.1 ml).
  • Performance of 31–39 injections with an ultra-fine 30–32G needle at 7 muscle groups according to the PREEMPT map.
  • Each injection is a gentle prick – patients describe it as a ‘pin prick’.
  • The entire procedure takes 10–15 minutes.
  • Brief post-procedure observation; discharge. The patient may return to normal activities.
  • First effect: 7–14 days. Full effect: 4–6 weeks. Repeat: in 12 weeks.

Preparation

  • Headache diary from the past 1–3 months (confirming indications in migraine)
  • No need to fast
  • Avoid aspirin and NSAIDs for 24h before the procedure (reduces bruising risk)
  • Keep normal hairstyle – avoid aggressive massage after the procedure
  • Immediately after: do not bend the head downward for 4 hours; do not lie down for 4 hours
  • Contraindications: pregnancy, myasthenia gravis, Lambert-Eaton syndrome, toxin allergy, injection site infection, confirmed endogenous antibodies against the toxin

Possible Side Effects

  • Minor pain at the injection site
  • Small bruises
  • Transient headache in the first 24–48h (paradoxically in 5–10% of patients)
  • Eyelid ptosis – rare, resolves within a few weeks
  • Neck muscle weakness (usually with excessively high doses at paraspinal injection sites)
  • Very rarely: distant toxin spread (at doses >600 units, well beyond the migraine protocol)

FAQ

When will I feel the effect of botulinum toxin for migraine?

First effect: 7–14 days after the first injection. Full effect: 4–6 weeks. A full assessment of efficacy requires 2–3 cycles (6–9 months of systematic treatment). Some patients experience significant improvement only after the second cycle – it is worth being patient.

Is botulinum toxin addictive? Does the effect weaken over time?

No – botulinum toxin is not addictive. On the contrary, long-term studies show CUMULATIVE efficacy – after each successive cycle the effect is often stronger or longer-lasting. After 5 years of systematic treatment, 90% of patients achieve significant headache reduction.

Can I continue other migraine medications alongside botulinum toxin?

Yes – botulinum toxin does not interact with acute medications (triptans, NSAIDs, gepants). It can also be combined with anti-CGRP antibodies (erenumab, fremanezumab, galcanezumab) in patients resistant to monotherapy.