Migraine Deep-Dive — Mechanism → Pain Relief

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Give a tight mechanistic explainer that **closes the loop from receptor → pathway → less pain** for both **acute** and **preventive** migraine options. Keep it plain-language, no tables. **First, the shared pain pathway (brief):** trigeminovascular activation → CGRP release → meningeal vasodilation + sterile neurogenic inflammation → peripheral/central sensitization → pain perception. **Acute mechanism → relief (map binding site → cellular → network effects):** • **Triptans** (5-HT1B/1D agonists) • **Lasmiditan** (5-HT1F agonist) • **Gepants** (CGRP-receptor antagonists) • **Riboflavin / Vitamin B2** (include here as a mechanistic contrast even though preventive) For each: say if it **causes vasoconstriction (Y/N)** and why that matters; connect to **time-to-relief** and **route** choices (oral/ODT/nasal/SC) in nausea/vomiting or severe attacks; give **one key safety/contra**; and note **MOH tendency/neutrality** if relevant. **Acute “bundle” / clinic-ED migraine cocktail (briefly, mechanism-linked):** Explain how combining a **dopamine-antagonist antiemetic** (e.g., prochlorperazine/metoclopramide) + **NSAID** (e.g., ketorolac) + **IV fluids ± magnesium** can act on different nodes of the pathway (nausea centers, inflammatory mediators, CGRP-linked vasodilation/sensitization, dehydration). Note typical **synergy**, common **adverse effects** (e.g., akathisia) and the rationale for **diphenhydramine co-use** to mitigate it. *(If details extend beyond the session content, label them as general clinical practice.)* **Preventive mechanism → fewer attacks (map class → core MOA → how sensitization/cortical hyperexcitability is reduced):** • **Beta-blockers** (metoprolol, propranolol, atenolol) • **ARB** candesartan • **Anti-seizure**: topiramate, valproate • **Antidepressants**: amitriptyline, nortriptyline, venlafaxine • **CGRP monoclonal antibodies**: erenumab, fremanezumab, galcanezumab; **eptinezumab** IV • **Preventive gepants**: rimegepant (qod), atogepant (daily) • **OnabotulinumtoxinA** (q12 weeks), **nerve blocks/devices** (mechanism sketch) • **Riboflavin/Vitamin B2**: tie mitochondrial electron transport support → improved neuronal energy homeostasis → less cortical hyperexcitability → fewer attacks. **Close with 3–5 rules-of-thumb** that tie mechanism to **who benefits & when to choose** (e.g., vascular disease → avoid vasoconstrictors; prominent nausea → non-oral routes/antiemetic-forward; high attack frequency → prevention threshold and which class to try first vs CGRP-targeted options). Keep it concise (≈12–18 bullets total) and make every step explain *how the mechanism yields less pain or fewer attacks*.

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