The Role of Allergies and Sinus Disorders in Headache & Facial Pain

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2 The Role of Allergies and Sinus Disorders in Headache & Facial Pain Vincent T. Martin, MD Professor of Medicine Co-director of the Headache & Facial Pain Center University of Cincinnati College of Medicine

3 Disclosures Allergan Speaker Teva Speaker Avenir Speaker Ely Lilly Consultant, Speaker Depomed Speaker Neuroscion Consultant

4 Sinus Headache Patients Fulfilled IHS Criteria for Migraine or Probable Migraine 2991 Patients Enrolled and Evaluated for IHS Diagnosis Migraine With or w/o Aura n= % Probable Migraine n=244 Tension n=239 Other n=112 4% 8% 8% % of Patients Schreiber CP et al. Arch Intern Med. 2004;164:

5 Perplexing Question Why is there such a high prevalence of migraine headaches in patients with sinus headache?

6 What disorders could account for sinus headaches? Migraine and TTH Rhinitis Allergic, non-allergic and mixed Acute and chronic rhinosinusitis Anatomical abnormalities of nose and sinuses Leading to mucosal contact points and/or sinusitis

7 Migraine Headache Activation of Cranial Parasympathetics

8 Ipsilateral Autonomic Symptoms in Migraine Patients from General Population Men Women Conjunctival Injection 31.9% 22.3% Tearing 49.9% 38.2% Nasal Congestion /Rhinorrhea 15.9% 19.1% Eyelid edema 13% 17.2% Miosis or ptosis 26.1% 16.6% Obermann M. Cephalalgia 2007; 27:

9 Activation of the TNC May Result in Reflex Activation of Cranial Parasympathetic Nerves Extending into Sinus Cavities and Tear Ducts

10 Proposed Pathogenesis Allergic and NA Rhinitis, Chronic Rhinosinusitis and Mucosal Contact Points

11 Trigeminal Anatomy and Physiology Sinuses and nares innervated by V1 and V2 distributions of trigeminal nerve Two main sensory nerves are the ethmoidal and nasopalatine nerves Project to spinal nucleus of TN

12 Summary of Wolff s Intranasal Stimulation Studies on Human Volunteers*

13 Pathophysiology Mucosal contact points from anatomic abnormalities of paranasal structures Vacuum headaches Peripheral release of inflammatory mediators (eg. histamine, PG s, leukotrienes) or neuropeptides

14 Allergy and Migraine Mast cell degranulation during a migraine attack Plasma histamine levels are increased in migraine during ictal and interictal time periods Intravenous allergen challenge in rats can induce plasma extravasation in the dural mater, which can be blocked by antihistamines Sicuteri F. Headache 1963; 3: Heatley R. Clinical Allergy 1982; 12: Markowitz S. Cephalalgia 1988; 8: 83-91

15 Theorized Pathogenesis Blood Vessel Nasal Mucosa Substance P CGRP NKA Allergens Mast Cell Histamine Interleukins TNFα C-fibers Trigeminal Nerve Substance P CGRP Gastrin Releasing Peptide

16 Rhinitis and Migraine Epidemiological Studies

17 Subtypes of Chronic Rhinitis Rhinitis Subtypes Allergic Rhinitis (AR) Mixed Rhinitis (MR) Non Allergic Rhinitis (NAR) Atopic Trigger Atopic + Non Atopic Trigger Non Atopic Trigger

18 Common Allergic and Non Allergic Triggers for Chronic Rhinitis Allergic Triggers Tree and Grass Pollens Animal dander (dogs, cats) Dust mites Molds Cockroach Non Allergic Triggers Perfumes Cigarette Smoke Gasoline Paint Cleaning agents (e.g. ammonia)

Controls 35 30 25 Allergy Practice Prevalence of

19 Prevalence of Migraine in Patients with Allergic Rhinitis vs. Controls Allergy Practice Prevalence of Migraine Allergic Rhinitis No Rhinitis Ku M. Ann Allergy Asthma Immunol 2006; 97:

20 Migraine Frequency in Chronic Rhinitis Patients vs. Controls Martin V. Abstract AHS Meeting 2012

21 Degree of Atopy Modulates the Frequency of Migraine in Patients with Allergic Rhinitis <45 years of Age Low Intermediate High Martin V. Headache 2011; 51: 8-20.

22 Immunotherapy Decreases the Frequency of Migraine Headache in Patients with Allergic Rhinitis <45 years of age Variable Risk Ratios (95% CI) P values Allergic Sensitization 45% Positive Allergy Tests >45% Positive Allergy Tests 0.80* (0.65, 0.99) 1.60* (0.11, 2.29) Immunotherapy 0.48 (0.28, 0.83) 0.01 Rhinitis Meds 1.55 (0.72, 3.35) 0.26 Migraine Preventatives 0.98 (0.48, 2.04) 0.97 Gender 0.72 (0.37, 1.38) 0.32 *Risk ratio corresponds to a 10% increase in allergic sensitization Martin V. Headache 2011; 51: 8-20

23 Chemosensation TRPV3 TRPV4 TRPV1 TRPV2 TRPM8 TRPA1 KCNK P2x ASIC Nav Cav Ky ATP 45oC Viana F. ACS Chemical Neurosci. 2011;2: Mechanical deforma2on Chemical s2mula2on Cold Temp 10oC

Dura Trigeminal nerve Mast Cell Inﬂammatory

24 Dura Trigeminal nerve Mast Cell Inﬂammatory mediators An2bodies Allergen Irritant Parasympathe2c nerve branch in the dura Substance P CGRP Trigeminal ganglion VIP Sphenopala2ne Sphenopala2ne ganglion Parasympathe2c nerve ganglion branch in the nose Mosimann BL, et al. J Allergy Clin Immunol. 1993;92: Goadsby PJ, et al. N Engl J Med. 2002;346:

25 Sinus Disorders and Headache Rhinosinusitis

26 Headache Attributed to Chronic or Recurring Rhinosinusitis A. Any headache fulfilling criterion C B. Clinical, nasal endoscopic or imaging evidence of current or past infection or other inflammatory conditions within the paranasal sinuses C. Evidence of causation demonstrated by at least two of the following: 1. Headache has developed in temporal relationship to the onset of chronic rhinosinusitis 2. Headache waxes and wanes in parallel with the degree of sinus congestion, drainage and other symptoms of chronic rhinosinusitis 3. Headache is exacerbated by pressure applied over the paranasal sinuses 4. In the case of unilateral rhinosinusitis, headache is located ipsilataeral to it D. Headache not better accounted for by another ICHD-3 diagnosis ICHD-3 Beta 2013

27 Symptom Outcomes After Endoscopic Surgery for Chronic Rhinosinusitis * * * Preoperatively Postoperatively Facial Pressure Headache Nasal Obstruction *P<0.05 pre vs. post Bhattacharyya N. Arch Otolaryngol Head Neck Surg 2004; 130:

28 Rhinologic Headaches Mucosal Contact Point Headaches

29 Case Presentation 36 y/o male Chronic TTH upon awakening in the left retro-orbital and temporal regions for 10 years Migraine with visual aura occurring 1-2X per week Snoring a/w respiratory infection Nasal steroids alleviated morning headaches

30 Deviated Septum to the Left

31 Scarupa M. Allergy Asthma Proc 2004; 25: Mucosal Contact Points

32 Mucosal Contact Point Headaches Intermittent pain localized to the peri-orbital and medial canthal or temporozygomatic regions Clinical, endoscopic and/or CT imaging evidence of mucosal contact points Evidence that pain can be attributed to mucosal contact points Abolition of pain after topical lidocaine Pain corresponds to gravitational variations in mucosal congestion Pain resolves within 7 days after surgical removal of mucosal contact point.

33 Mucosal Contact Points in Migraineurs Retrospective review of 21 patients Inclusion Refractory or transformed migraine Mucosal contact point Improvement with topical anesthetic All underwent endoscopic sinus surgery Outcome measures Headache days per month 17.7 to 7.7 (p<0.01) Headache severity 7.8 to 3.6 (p<0.001) Headache disability 5.6 to 1.8 (p<0.0001) Behlin F. Cephalalgia 2005; 25:

34 Pathophysiology of Rhinologic Headaches Mechanisms of Headache Mucosal Contact Points Chronic Sinusitis/ Rhinitis Vacuum Phenomenon Direct Activation of Trigeminal Afferents Headache

35 Pathophysiology Modulate other disorders that could affect headaches Obstructive sleep apnea Insomnia Depression

36 Two or Three Hit Theory Migraine Headache Allergies Mucosal Contact Points and/or Chronic Rhinosinusitis

37 Questions Is migraine only a disorder involving V1? Can rhinitis, chronic rhinosinusitis or mucosal contact points be a secondary cause of migraine or TTH? Do these disorders simply modulate underlying migraine or TTH or have no role?

38 Conclusions A diagnosis of migraine headache is very common in those with sinus symptoms. Challenge to audience to ask question: Why? Need to remain open minded about the possibility that nasal and sinus disorders could be modulating headache in your patients!

Headache Master School Japan-Osaka 2016 II. Management of refractory headaches Case Presentation 2. SUNCT/SUNA: concept, management and prognosis

$Headache Master School Japan-Osaka 2016 II. Management of refractory headaches Case Presentation 2. SUNCT/SUNA: concept, management and prognosis$ Headache Master School Japan-Osaka 2016 II. Management of refractory headaches Case Presentation 2. SUNCT/SUNA: concept, management and prognosis Noboru Imai(Department of Neurology, Japanese Red Cross