This article on headache disorders is part of a 12-part series on the most commonly billed diagnoses in primary care outpatient settings. A list of the top 12 billed diagnoses was compiled from information obtained from the CDC and the Centers for Medicare and Medicaid Services (CMS).1,2 Each article explores the pathophysiology of disease to gain an in-depth understanding of the process. Disease pathophysiology helps NPs understand the whys: why certain clinical manifestations are present, why specific diagnostic tests are ordered, and why treatments are chosen. This article will review the pathophysiology, clinical manifestations, diagnostic testing, and treatment options for the three most common types of headache disorders in adults.
Headache disorders are among the most common syndromes of the nervous system, but remain underestimated, underdiagnosed, and undertreated.3,4 Primary headache disorders include migraines, tension-type headaches, and trigeminal autonomic cephalgias including cluster headaches. Although usually benign, headaches can be a symptom of a more serious structural abnormality or systemic disease. Secondary headaches are caused by underlying medical conditions such as brain tumor, meningitis, sinusitis, giant cell arteritis, and cerebral vascular disease.4 The pathophysiology, clinical manifestations, and treatment for secondary headaches is outside the scope of this article.
Headache disorders are estimated to affect up to 50% of the global population. Additionally, up to 4% of the world's adult population suffers from a headache on 15 or more days each month.3 In the US, 14.2% of adults reported having a migraine or severe headache in the past 3 months, and headache complaints led to 3.1% of all ED visits from 2009 to 2010.5 Episodic tension-type headaches are reported to affect almost 80% of the total population, whereas chronic tension-type headaches occur in less than 5% of the population.6 Cluster headaches are relatively rare, occurring in only 0.1% of the population, but can be quite severe.7 Recurrent headaches whether migraine, tension-type, or cluster are associated with decreased quality of life, financial burden, and increased levels of disability. In fact, headache disorders are the third leading cause of years lived with disability.3
Migraines. The pathophysiologic basis of a migraine is not well established; however, it involves complex neurologic processes and affects multiple areas and functions (autonomic, affective, cognitive, and sensory) of the brain. Migraines are associated with multiple genetic and environmental factors; additionally, current theories suggest neurologic, vascular, and hormonal aspects, as well as neurotransmitter-mediated changes in the brain.4
Migraines are often precipitated by triggers such as chemicals (alcohol or nitrates) and changes in sleep patterns, diet, and hormones.4 Migraine attacks often begin with a prodromal phase and aura. The direct mechanism by which the prodromal period initiates the headache is unclear. The pain associated with a migraine is thought to occur from the excitation of the nociceptors in the meninges.8,9 Migraine aura is suggested to be caused by a gradual depolarization or excitation in cortical neurons and glia followed by hyperpolarization or inhibition.9 Pain-producing inflammatory substances are released during a migraine. These elements affect the nerves and blood vessels of the brain.3 Interestingly, the brain of a person who has migraines has been found to have structural, functional, and chemical differences from the brain of a person who does not have migraines.9,10
Cluster headaches. Although there is currently no clear understanding of the source related to cluster headaches, the trigeminovascular system, the parasympathetic nerve fibers of the trigeminal autonomic reflex, and the hypothalamus are involved.7,11 Trigeminovascular activation leads to the release of vasoactive neuropeptides and the formation of neurogenic inflammation, which initiates the pain cycle.4,12 Activation of the parasympathetic nervous system during a cluster headache activates the trigeminal autonomic reflex. This leads to clinical manifestations such as lacrimation, nasal congestion, and rhinorrhea.12 Hypothalamic involvement is under investigation as a related source, since there appears to be a natural internal process that stimulates interval recurrence of cluster headaches.7,11 Research studies report other possible causes are related to dysregulation of the autonomic nervous system or a defect in the central pathway of pain control.7
The genetic component has many possible sources such as PER3 (a circadian rhythm gene), orexin-B (neuropeptide that regulates arousal), and pituitary adenylate cyclase-activating peptide (PACAP) (a receptor gene, its main role is vasodilation).7,12 Orexin-B is involved in the modulation of nociceptive neurotransmission and therefore associated with the physiologic processes involved in pain transmission.7,12
Tension-type headaches. Tension-type headaches are caused in part by neurobiologic stimuli. The pathophysiologic process involves the central nervous system and the hypersensitivity of pain fibers originating from the trigeminal nerve.4,6 This leads to deficits in the descending inhibitory pain pathways located in the brainstem.4 A peripheral component also plays a role in the development of tension-type headaches as muscular sensitivity may be caused by the peripheral sensitization of myofascial sensory afferents.4 Central mechanisms expressed as central sensitivities have also been implicated to play a role in chronic tension-type headaches.13 Other associative influences include: psychological, environmental, and genetic factors.6,13 Recent studies on genetics suggest a familial tendency with an inherited susceptibility.13
History, physical exam, and diagnosis
A patient's history is an important component in determining the diagnosis. The onset, timing, duration, location, quality, and severity of headache symptoms should be documented as well as associated symptoms and precipitating or aggravating factors.14,15 A thorough history should include the presence of environmental or other known risk factors for headache disorders, such as family history of headache disorders, tobacco use, diet, alcohol consumption, recreational drug use, and stress at home or work. The APRN must be cognizant of secondary causes of headache that may include hypertension, space-occupying lesions, vascular issues or malformations, and hemorrhagic or ischemic stroke, among others. The first article in this series provides information on hypertension. Finally, current and previous treatment regimen(s), response to treatment(s), and medication adherence must be documented.15
The physical exam should focus on a thorough neurologic assessment and areas identified as abnormal in the history. The patient's vital signs should be obtained and documented. If a patient has an elevated BP, a second reading from the opposite extremity must be taken. The neurologic exam is essential and includes the evaluation of mental status; cranial nerves; tenderness with palpation of head, neck, or cervical muscles; nuchal rigidity; limitations with mobility or motor function; decreased sensation, coordination, or reflexes; and any gait abnormalities. A fundoscopic exam must be conducted and any abnormalities such as papilledema or acute glaucoma documented. The temporomandibular joint can be palpated to determine any dysfunction. Red flags that warrant referral to the ED for emergent diagnostic testing to rule out secondary causes of headache include: vision changes, thunderclap onset (abrupt onset of severe headache), fever, neck stiffness, papilledema, focal neurologic deficits such as weakness, paresthesias, speech changes, reduced level of consciousness or confusion, acute glaucoma, temporal arteritis, head injury, or seizure activity.14-16 Other symptoms that require close follow-up in office, possible diagnostic imaging, and possible referral to neurology include: a headache with new onset after age 50 years, pain that is worse in the morning upon awakening or awakens individual from sleep, auditory changes, pain that occurs with activity, or headaches that do not resolve with medication use.15,16
Migraines. A migraine is described as a unilateral, throbbing pain of moderate-to-severe intensity, which may worsen with activity and generally lasts 4 to 72 hours. Some patients may have prodromal and/or postdromal phases. At least one of the following must be associated with migraine headache and documented: nausea and/or vomiting, or photophobia and phonophobia.4 Migraines can occur with or without aura. Migraine aura generally occurs within 1 hour before the headache begins and may include temporary vision changes (blind spots, zigzag lines, flashes of light, shimmering) or other disturbances such as numbness, speech or language difficulty, or muscle weakness. Migraine aura typically lasts from a few minutes up to 1 hour. Migraines are more common in women due to hormonal influences.3 Onset typically occurs at puberty and is most prevalent in those aged 35 to 45.
Cluster headaches. Cluster headaches occur unilaterally and are excruciatingly severe. Pain is generally orbital, supraorbital, and/or temporal.17 Autonomic manifestations ipsilateral to the side of the pain including lacrimation, conjunctival injection, eyelid edema, ptosis, nasal congestion, or rhinorrhea usually accompany a cluster headache.4,7 During attacks, patients may be restless or agitated.7 The attacks themselves can occur as often as every other day up to eight times daily and often occur around the same time each day.4 Cluster cycles are the periods during which attacks occur and can go on for days to months before a period of remission.4 Men between ages 20 and 50 have the highest incidence rate of attacks, and 85% of all patients diagnosed with a cluster headache are cigarette smokers.4,7 Family history plays a large role in differentiating a cluster headache from other headache types. Patients with a first-degree relative diagnosed with cluster headaches are 18 times more likely to be diagnosed with cluster headaches.7
Tension-type headaches. Tension-type headaches are the most common primary headache disorder and the most common neurologic disease in the world.3,6 Tension-type headaches may begin in one's teenage years and are most common between age 35 to 40, but occur in all age groups.3,4,6 The primary characteristic of a tension-type headache is the sensation of a tight band or pressure around the head.3,4 Pain onset is gradual and typically classified as a mild-to-moderate bilateral headache.4 Episodic tension-type headaches usually will last for a few hours, but may persist longer.3
Because the diagnosis of migraine, cluster, and tension-type headaches is clinical, neuroimaging is not recommended in patients with recurrent headache disorders who have a normal physical exam, do not present with red flags, and exhibit clinical features of migraine.7,15 Patients presenting with red flags requiring emergent diagnostic studies such as head computed tomography (CT) scan, MRI, and vascular imaging should be referred to the emergency room for evaluation.14,16 Vascular imaging studies are used to visualize and evaluate intracranial vascular structures. It is important to note that reevaluation and possible diagnostic studies may be indicated in a patient who reports changes in headache character.18
A headache questionnaire should be completed by patients presenting with a chief complaint of headache.7 A questionnaire for cluster headaches, which inquired about headache duration and autonomic symptoms was found to have a sensitivity of 81% and specificity of 100%.7 There are no definitive lab tests to diagnosis headache disorders, however the following labs are beneficial to rule in/out possible contributing causes, including complete blood cell count, comprehensive metabolic panel, fasting blood glucose, serum creatinine, and thyroid-stimulating hormone.
Treatment for headache disorders is guided by several different guidelines and recommendations.15,19 An overview of the treatment regimen for the three types of headache disorders is provided.
Migraines. Avoiding triggers is an important component of managing migraines. Stress management and lifestyle changes can reduce the incidence of migraines.14 Medications used for acute treatment of migraines include nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, dihydroergotamines, opioids, and antiemetics.14,20 A wide variety of preventive medications are also available for use and include beta-blockers, calcium channel blockers, tricyclic antidepressants, certain antiepileptic drugs, injection of onabotulinumtoxinA (botulinum toxin, Botox), and calcitonin gene-related peptide (CGRP) monoclonal antibodies.14 Some studies have demonstrated that cognitive-behavioral interventions for treatment of insomnia can reduce migraine frequency in patients with chronic migraine.21 Evidence also demonstrates that behavioral interventions, such as relaxation training, stress management, cognitive-behavioral therapy, and biofeedback are effective treatments for migraines.22 Individuals with chronic migraine unresponsive to medical treatment and patients presenting with aura should be evaluated by a specialist.4 Patients presenting with aura should be referred to a neurologist to determine if a more serious condition is present, since there is a mildly increased risk of stroke.14
Cluster headaches. Acute cluster headache treatment includes oxygen and use of subcutaneous or intranasal triptans.11,23,24 Other treatments available for acute cluster headaches include intranasal lidocaine and subcutaneous, I.V., or intranasal dihydroergotamine.23,24 Preventive therapy includes verapamil and may require several weeks of therapy and dose increases until prophylaxis of headache is achieved.11 Several other medications including topiramate, lithium, and melatonin have demonstrated possible benefit for prevention of cluster headaches in limited studies and case series.24 Cluster headaches can be managed by an NP with a number of pharmacotherapies; however, an early specialist referral is recommended because this headache type is uncommon, disabling, and challenging to manage.15 Referral is also necessitated for procedural treatments.15
Tension-type headaches. Tension-type headaches may be treated effectively with ice and NSAIDs as needed.4 Patients experiencing chronic tension-type headaches may benefit from counseling or psychologist referral for cognitive-behavioral and relaxation therapy.4 Daily use of a tricyclic antidepressant has shown benefits in patients with tension-type headaches, however, this is an off-label use.4 A referral to a neurologist or psychiatrist may be warranted for individuals that require medication adjustments or multimodal therapies. Long-term use of analgesics, muscle relaxants, antihistamines, tranquilizers, caffeine, and ergot alkaloids have not shown to be effective for treatment.4
The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) is a morbidity classification published by a joint effort between the CMS and the National Center for Health Statistics.25 The ICD-10-CM is the standard billing code system that is used to submit diagnosis codes for insurance reimbursement.
The ICD-10-CM diagnosis code for headache is R51 and can be used as a diagnosis for reimbursement purposes.25 Migraines are listed under the ICD-10-CM codes starting with G43. Other headaches such as cluster headaches and tension-type headaches are classified with code G44.25 Supportive information documented within the patient's chart provides justification for specificity, which increases reimbursement. (See ICD codes.)
Implications for practice
The role of the APRN in managing primary headache disorder includes:27
- obtaining a thorough history
- performing a physical exam including a complete neurologic assessment
- monitoring for red flags
- initiating appropriate referrals
- initiating and managing prescribed therapy, which includes acute and/or prophylactic medications, as well as monitoring for medication overuse
- educating patients on disease process, controlling triggers, treatment, and lifestyle modifications.
Headache disorders are a common complaint within the primary care setting and are often misdiagnosed or undertreated, causing patients significant burden. NPs play a significant role in providing patients with a collaborative approach to care, increasing follow-up opportunities, and maintaining a judicious focus on cost-effective treatment.28 NPs should consider social, cultural, economic, and psychological aspects when providing holistic care to patients.
1. Centers for Medicare and Medicaid Services. ICD-10 clinical concepts for family practice. 2015. www.cms.gov/Medicare/Coding/ICD10/Downloads/ICD-10FamilyPracticeClinicalConcepts20170324.pdf
2. Rui P, Hing E, Okeyode T. National ambulatory medical care survey: 2014 state and national summary tables. 2014. www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf
4. McCance KL, Heuther SE. Pathophysiology: The Biologic Basis for Disease in Adults and Children
. 8th ed. St. Louis, MO: Elsevier; 2019.
5. Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine
and severe headache in the United States: updated statistics from government health surveillance studies. Headache
6. Sobieski M, Korzeniewska A. Tension-type headache
– most prevalent, still unknown. World Sci News
7. Kandel SA, Mandiga P. Cluster headache
. [Updated 2019 Oct 22]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020.
8. Noseda R, Burstein R. Migraine
pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain
. 2013;154(suppl 1):S44–S53.
9. Burstein R, Noseda R, Borsook D. Migraine
: multiple processes, complex pathophysiology. J Neurosci
10. Borsook D, May A, Goadsby P, Hargreaves R. The Migraine Brain: Imaging Structure and Function
. 1st ed. New York, NY: Oxford University Press; 2012.
11. May A, Schwedt TJ, Magis D, Pozo-Rosich P, Evers S, Wang S-J. Cluster headache
. Nat Rev Dis Primers
12. Buture A, Boland JW, Dikomitis L, Ahmed F. Update on the pathophysiology of cluster headache
: imaging and neuropeptide studies. J Pain Res
13. Mier RW, Dhadwal S. Primary headaches. Dent Clin North Am
15. Becker WJ, Findlay T, Moga C, Scott NA, Harstall C, Taenzer P. Guideline for primary care management of headache in adults. Can Fam Physician
17. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia
18. Evans RW, Burch RC, Frishberg BM, et al. Neuroimaging for migraine
: The American Headache Society systematic review and evidence-based guideline. Headache
19. American Headache Society. The American Headache Society Position Statement on integrating new migraine
treatments Into Clinical Practice. Headache
20. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine
in adults: the American Headache Society evidence assessment of migraine
21. Smitherman TA, Kuka AJ, Calhoun AH, et al. Cognitive-behavioral therapy for insomnia to reduce chronic migraine
: a sequential Bayesian analysis. Headache
22. Rains JC, Penzien DB, McCrory DC, Gray RN. Behavioral headache treatment: history, review of the empirical literature, and methodological critique. Headache
. 2005;45(suppl 2):S92–S109.
23. Obermann M, Holle D, Naegel S, Burmeister J, Diener H-C. Pharmacotherapy options for cluster headache
. Expert Opin Pharmacother
24. Pomeroy JL, Marmura MJ. Pharmacotherapy options for the management of cluster headache
. Clin Med Insights
25. ICD-10-CM Official Guidelines for Coding and Reporting. 2020. www.cdc.gov/nchs/data/icd/10cmguidelines-FY2020_final.pdf
27. Prettyman A, Greco K, Cook C, Padden D, Van Duyn K. Guideline for primary care management of headaches in adults. American Association of Nurse Practitioners
28. Himmelfarb CRD, Commodore-Mensah Y, Hill MN. Expanding the role of nurses to improve hypertension care and control globally. Ann Glob Health