The Genesis of Pain in Migraine Anna Andreou The Headache Centre Wolfson Centre, King’s College London & Guy’s & St Thomas's NHS Foundation Trust Headache Centre

Migraine – More Than a Pain Disorder A clinical syndrome characterised by headache with specific features and associated symptoms Structural Functional Behavioural Environmental Nausea/Vomiting Sensory disturbances Poor Concertation Limited Activities Disability Craving Yawning Fluid retention Heighten Perception Hangover Anorexia Tired Diurisis Visual changes Speech difficulties Confusion Numbness Multifactorial predisposition Multifactorial predisposition Interictal Phase Premonitory Aura Headache Postdrome Interictal phase Adapted from Blau JN. Lancet 1992; 339: 1202–7

How is Migraine Headache Generated Following Hypothalamic Activation? Other brain areas Hypothalamus Migraine pain pathways Premonitory phase Attack progression Migraine Headache

The Hypothalamus- A Brain in the Brain

Our Results: Migraine-Triggering Substances Change the Activity of the A11 Hypothalamic Nucleus Migraine-Triggering Substances in the A11 Hypothalamic Nucleus Facilitate the Migraine Pain Pathway Many hypothalamic chemicals change their activity during experimental induction of a migraine

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Guy’s and St Thomas’ NHS Trust & King’s College London How does Single Pulse Transcranial Magnetic Stimulation (sTMS) Prevent Migraine? Joseph Lloyd Headache Research Lab The Headache Centre Guy’s and St Thomas’ NHS Trust & King’s College London

sTMS in the Acute and Preventive Treatment of Migraine ? Underlying Mechanism of Action in the Treatment of Acute Migraine ? Acute Treatment Lipton et al. Lancet Neurol,2010; 9(4): 373-380 Preventive Treatment Bhola et al., JHP 2015;16:535 Starling et al., Cephalalgia 2018, Vol. 38(6) 1038–1048

GSTT data Demographic and clinical characteristics at baseline of 42 migraine patients treated with sTMS Sex, M/F 5/37 Age (y), mean ± SD 43 ± 19 Aura, N (%) 11 (26.2%) Chronic migraine/High frequency episodic migraine 37/5 Failed Botox, N (%) 20 (47.6) Headache days 14.7 Migraine days 11.1 HIT-6 63.3 MTIS18- 179

? Underlying Mechanism of Action in the Treatment of Acute Migraine ? Non –Invasive Single Pulse Transcranial Magnetic Stimulation – A Cortical Treatment for Migraine ? Underlying Mechanism of Action in the Treatment of Acute Migraine ? The long history of developing a portable sTMS device Future http://www.med.upenn.edu

sTMS Mechanism of Action in Migraine ? Underlying Mechanism of Action in the Treatment of Acute Migraine ? 11 mm rodent sTMS coil Andreou et al, Brain, 2016; 139(7): 2002–2014

sTMS can influence hypothalamic activity in A11 dopaminergic nucleus Our Results: sTMS can influence hypothalamic activity in A11 dopaminergic nucleus sTMS effect on hypothalamic activity is consistent and cumulative

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