Headache Disorders PDF

Headache Disorders Marissa Hakala, PharmD Recognize components of the trigeminovascular system Explain the role of CGRP and the trigeminovascular system in mi...

Headache Disorders Marissa Hakala, PharmD Recognize components of the trigeminovascular system Explain the role of CGRP and the trigeminovascular system in migraine Objectives Recognize the role of pain sensitivity in tension headache Describe the three structures involved in cluster headaches Differentiate between clinical signs and symptoms of migraine, tension headache, and cluster headache. Trigeminovascular System Trigeminal Nerve Cranial nerve V Three divisions: Ophthalmic division (V1) Maxillary division (V2) Mandibular division (V3) Touch, proprioception, pressure, vibration, and nociception from face Nociception from meninges and brain blood vessels Trigeminovascular System Contained within V1 division Innervates brain blood vessels and meninges Joins with somatosensory peripheral neurons that innervate periosteum and muscles Associated with headaches Neuropeptides: calcitonin gene-related peptide (CGRP), substance P, neurokinin A Role in cerebral blood flow Activated unipolarly 5 https://www.researchgate.net/figure/A-schematic-illustration-of-potential-sites-of-CGRP-secretion-from-trigeminal- 6 ganglion_fig1_305732362  Migraine Migraine Phases Postdrome Aura Phase* Neck pain Pain Phase Fatigue Nausea and Visual disturbance* vomiting Tiredness Mood/cognitive effects Numbness and Sensory sensitivity Concentration tingling impairment Food cravings Mumbling or slurred speech Premonitory Headache Phase Phase 9  https://americanmigrainefoundation.org/resource-library/understanding-migraine-aura/ 10 https://www.tfw2005.com/boards/threads/scintillating-scotoma-ocular-migraine-retinal- https://americanmigrainefoundation.org/resource-library/understanding-ocular-migraine/ migraine.1116225/ Cortical Spreading Depolarization Transient wave of neuronal depolarization Hyperexcitability due to glutamate and/or extracellular potassium Associated with aura symptoms 11 Neuropeptides and Neurotransmitters CGRP, substance P, neurokinin A Released at vascular terminals of trigeminal nerve Stimulate mast cells  release histamine and prostaglandins Promote vasodilation and dural plasma extravasation Neurogenic inflammation  activation of pain receptors Serotonin Involved in cortical excitability and vasoconstriction Decreased levels in migraine  vasodilation 12  Trigeminovascular System in Migraine o Trigeminovascular input from meningeal vessels o Passes through trigeminal ganglion o Synapses on trigeminocervical complex (TCC)  thalamus o Results include: o Photosensitivity o Cutaneous allodynia 13 Brain Activity Changes and Related Symptoms Premonitory changes in hypothalamic function  polyuria, mood change, appetite change Increased activity in occipital cortex  photosensitivity Activation of brainstem  nausea 14 Clinical Features Tension-type Migraine Cluster headache headache Usually 4-6 hours, up 5 min – 3 hours Duration 4-72 hours to 1 week Up to 8 episodes/day Location Unilateral Bilateral Unilateral Pain severity Moderate-severe Mild-moderate Severe Band-like, non- Stabbing, burning, Pain description Pulsatile pulsating sharp Rhinorrhea, lacrimation, 15 Other symptoms Nausea, vomiting, aura conjunctival hyperemia,  Medications Abortive Therapies Preventative Therapies Analgesics Aspirin, diclofenac, ibuprofen, naproxen, Antiseizure Valproate, divalproex, topiramate, and NSAIDs celecoxib, acetaminophen, medications carbamazepine, gabapentin acetaminophen/aspirin/caffeine Triptans Sumatriptan, zolmitriptan, naratriptan, Antidepressants Amitriptyline, venlafaxine rizatriptan, almotriptan, frovatriptan, eletriptan Ergots Ergotamine tartrate and Beta blockers Metoprolol, propranolol, timolol, dihydroergotamine atenolol Antiemetics Metoclopramide and prochlorperazine Anti-CGRP Erenumab, fremanezumab, antibodies galcanezumab, eptinezumab Ditans Lasmiditan CGRP Atogepant, rimegepant antagonists CGRP Ubrogepant, rimegepant, zavegepant NSAIDs * For migraines with predictable antagonists pattern, such as menstrual migraines Opiates Codeine or tramadol + acetaminophen, Miscellaneous Lisinopril, candesartan, verapamil,16 butorphanol botulinum toxin type A Tension-Type Headache (TTH) Triggers MUSCLE SLEEP DEHYDRATION STRESS TIGHTNESS DEPRIVATION 18 Origin of Pain Muscular nociceptors Input from myofascial structures via trigeminal ganglion and dorsal horns of spinal cord at C1 to C4 ** Little effect from cerebral vasculature ** 19 20 Increased Pain Sensitivity In chronic pain, there may be abnormal sensitivity of A-beta fibers Hyperalgesia – exaggerated response to painful stimuli Allodynia – pain response to non-painful stimuli Seen in chronic TTH Myofascial trigger points Muscle areas with hypersensitivity to pressure Cause referred pain Seen in pattern consistent with TTH Central sensitization Trigeminal nucleus, dorsal horn, thalamus Hypersensitivity at non-head/neck areas 21 https://openbooks.lib.msu.edu/neuroscience/chapter/somatosensory-systems/  Molecular Mechanisms Nitric oxide Induces headaches Inhibition of nitric oxide synthase  reduced headache intensity Thought to cause central sensitization at trigeminal nucleus Serotonin, CGRP, substance P, etc also may be involved 22 Clinical Features Tension-type Migraine Cluster headache headache Usually 4-6 hours, up 5 min – 3 hours Duration 4-72 hours to 1 week Up to 8 episodes/day Location Unilateral Bilateral Unilateral Pain severity Moderate-severe Mild-moderate Severe Band-like, non- Stabbing, burning, Pain description Pulsatile pulsating sharp Rhinorrhea, lacrimation, 23 Other symptoms Nausea, vomiting, aura conjunctival hyperemia, Medications Abortive Therapies Preventative Therapies Analgesics Acetaminophen, aspirin, diclofenac, Antidepressants Tricyclic antidepressants, mirtazapine, and NSAIDs ibuprofen, naproxen, ketoprofen, venlafaxine ketorolac Barbiturates Butalbital + aspirin or acetaminophen Antiseizure Topiramate, gabapentin medications Opiates Codeine + acetaminophen Muscle relaxers Tizanidine Injections Lidocaine, botulinum toxin 24  Cluster Headache 26 Hypothalamus Attacks have circadian and seasonal pattern Activation of ipsilateral inferior hypothalamic gray matter Stimulation of hypothalamus  remission of attack Patients with cluster headache have reduced melatonin peak Orexin may be involved in trigeminal pain modulation 27 Trigeminovascular System CGRP released Activates parasympathetic system through the superior salivatory nucleus 28 Parasympathetic Activation Pass through sphenopalatine ganglion  periphery Conjunctival injection, lacrimation, rhinorrhea, cranial and extracranial vasodilation Release vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) PACAP – vasodilating effects 29 30  Clinical Features Tension-type Migraine Cluster headache headache Usually 4-6 hours, up 5 min – 3 hours Duration 4-72 hours to 1 week Up to 8 episodes/day Location Unilateral Bilateral Unilateral Pain severity Moderate-severe Mild-moderate Severe Band-like, non- Stabbing, burning, Pain description Pulsatile pulsating sharp Rhinorrhea, lacrimation, 31 Other symptoms Nausea, vomiting, aura conjunctival injection, restlessness Medications Abortive Therapies Preventative Therapies Oxygen Calcium channel Verapamil blockers Triptans Sumatriptan, zolmitriptan Anti-CGRP Galcanezumab antibodies Ergotamine Dihydroergotamine, ergotamine tartrate Mood stabilizers Lithium derivatives Miscellaneous Lidocaine, octreotide Corticosteroids Prednisone Miscellaneous Topiramate, divalproex, melatonin, indomethacin, long-acting triptans, capsaicin 32 Clinical Features - Comparison Tension-type Migraine Cluster headache headache Usually 4-6 hours, up 5 min – 3 hours Duration 4-72 hours to 1 week Up to 8 episodes/day Location Unilateral Bilateral Unilateral Pain severity Moderate-severe Mild-moderate Severe Band-like, non- Stabbing, burning, Pain description Pulsatile pulsating sharp Rhinorrhea, lacrimation, 33 Other symptoms Nausea, vomiting, aura conjunctival injection, restlessness  Marissa Hakala, PharmD PGY2 Psychiatric Pharmacy Questions? Resident Capt James A Lovell FHCC [email protected] 34