Chronic Migraine — The 15-Day Threshold
Fifteen or more headache days a month defines chronic migraine.
- 15+: Chronic Migraine Threshold (headache days / month)
- 8: Episodic vs Chronic Cutoff (migraine days / month)
- 1–2%: Global Prevalence (of adults)
- #2: Disability Ranking (leading cause worldwide)
Defining chronic migraine
Fifteen-plus headache days monthly, eight migrainous, for three months.
Why prevention matters
Frequent attacks drive disability, medication overuse, and lost function.
PREEMPT Protocol — 31 Fixed Injection Sites
155 units of onabotulinumtoxinA delivered across seven muscle groups.
- 31: Total Injections (fixed sites)
- 7: Muscle Groups (head and neck)
- 155U: Total Dose (onabotulinumtoxinA)
- 12 wks: Session Interval (repeat cycle)
Seven muscle groups
Frontalis, corrugator, procerus, temporalis, occipitalis, cervical, trapezius.
Fixed-site, fixed-dose design
Every session repeats the same 31 sites, same 5U-per-site dose.
Toxin Binds Nerve Terminals — SNAP-25 Cleavage
Botulinum toxin cleaves SNAP-25, blocking acetylcholine vesicle fusion.
- SNAP-25: Target Protein (SNARE complex)
- Cleaves: Mechanism (blocks ACh release)
- 1–2 wks: Onset (clinical effect)
- ~12 wks: Duration (per session)
SNARE complex disruption
Cleaved SNAP-25 stops vesicles from docking and releasing acetylcholine.
Beyond acetylcholine
Toxin also blocks peripheral release of pain neuropeptides like CGRP.
Peripheral Sensitization Reduced
Blocked terminals lower nociceptive input into the trigeminal system.
- ↓: Nociceptor Signaling (peripheral sensitization)
- ↓: Central Sensitization (downstream effect)
- Calmed: Trigeminovascular System (less activation)
- Reduced: CGRP Release (neuropeptide signaling)
Peripheral to central
Less peripheral firing gradually quiets central trigeminal sensitization.
A cumulative effect
Sensitization drops further with each repeated 12-week cycle.
Reduced Headache Days — Cumulative Benefit
Two to three cycles compound the drop in monthly headache days.
- -8.4: PREEMPT Trial Reduction (headache days / month)
- ~70%: Responder Rate (≥50% improvement)
- 2–3: Cycles To Full Effect (12-week cycles)
- 2010: FDA Approval (chronic migraine indication)
Cumulative cycle effect
Each cycle builds on the last — benefit grows through cycle three.
Adherence matters
Skipping sites or delaying sessions blunts the cumulative benefit.