An Update on Diagnosis and Pharmacologic Therapy for Headache in the Oral and Maxillofacial Surgery Practice

Headaches are synonymous with neurovascular pain (cephalalgias), which comprise a heterogeneous group of pain disorders that share a common anatomic region (head and neck). Headaches are often a “universal” disease presentation that is evaluated by the oral and maxillofacial surgeon. Pharmacologic therapy of headaches is most often based on the severity of symptoms and the degree of disability experienced by the patient. This article describes the epidemiology of neurovascular headaches, their pathophysiologic mechanisms/presentation, the workup of patients, and an up-to-date overview of pharmacologic approaches that can be applied in the oral and maxillofacial surgical practice to treat this patient population.

Key points

  • The World Health Organization characterizes headaches among the major etiologies of disability that are underestimated and undertreated throughout the world.

  • The International Classification of Headache Disorders provide the most recent description of headache type and diagnosis based on the individual pathologic presentations of primary and secondary headaches.

  • Primary headaches refer to those without a clear causation due to pathology, trauma, or systemic etiology. These headaches include migraine, tension-type, and trigeminal autonomic cephalgias.

  • Medication overuse headache from either prescribed or over-the-counter drugs is very common in patients with chronic migraine. Preventive strategies and education remain the most important treatment modalities.

  • Research into the pharmacology of headache has led to several highly effective new treatments that are targeting the central nervous immune system with less adverse effects and more specific neuron-directed targets for pain relief.


The World Health Organization characterizes headaches among the major etiologies of disability with a global prevalence rate of 47%. Almost one-half of the adult population have had a headache at least once per year, and as such, headaches have been underestimated and undertreated throughout the world. , Ancient descriptions of headaches date back to 1200 bc and archeologic skull artifacts exhibit areas of surgical exposure for headache treatment in the writings of Hippocrates. The contemporary worldwide prevalence of a chronic daily headache can vary from 3% to 5% diagnosed and most likely represents chronic migraine. ,

Headaches are synonymous with neurovascular pain (cephalalgias), which comprise a heterogeneous group of pain disorders that share a common anatomic region, that is, the head and neck. The oral and maxillofacial surgeon (OMFS) receives consults from many of their medical colleagues to evaluate the chief complaint of a headache. Headaches are often a “universal” disease presentation that is evaluated by the OMFS because many referral physicians equate symptomatology with either an odontogenic nidus or temporomandibular disorder (TMD). There is a new paradigm shift in the understanding of the pathophysiology of headaches based on neuropathic mechanisms that warrant traditional and innovative pharmacologic management strategies. The objective of this article is to describe the epidemiology of neurovascular headaches, their pathophysiologic mechanisms/presentation, the workup of patients, and an up-to-date overview of pharmacologic as well as nonpharmacologic approaches that can be applied in the oral and maxillofacial surgical practice.

Literature search

A literature search was undertaken using Medline within the PubMed Portal to choose articles within the last 25 years. Only articles in English were chosen for inclusion. Each article’s bibliography was evaluated for relevant publications and reviewed by the authors for inclusion. The keywords chosen include “Headache,” “Primary and secondary headaches,” “International Classification of Headache Disorders (ICHD),” “Neurovascular headache/pain,” “Migraine,” “Adult and pediatric headache,” “Pharmacologic therapy for headaches,” Non-pharmacologic headache therapy,” “Pathology of headaches,” “medication headache overuse,” and “medications for headache treatment.” The level of evidence chosen was based on Sacket’s hierarchy of evidence and was predominantly level 1A, 2A, 3A, 4, and 5. Sixty articles that were relevant to this review were chosen. Additional references were chosen to support a paradigm shift in the pharmacology of headache therapy moving forward.


The lifelong prevalence of headaches is at 96% in men and women are disproportionately affected 3:1. The global prevalence rate of a tension-type headache (TTH) is 40% followed by the migraine at 15% to 18%. The common neurovascular headache type of migraine occurs more commonly in women (3:1) between the ages of 23 and 55 years. , Approximately, 44.5 million adults in the United States have experienced a migraine and the cost of treatment is at 17 billion dollars and 13 billion dollars in lost productivity. , The trigeminal autonomic cephalgias (TACs; ie, cluster headaches [CHs]) are the third most common type of headache with a prevalence rate of 0.1% and a gender ratio of male to female at 3:5 to 7:1. The International Classification of Headache Disorders (ICHD) provide the most recent description of headache type and diagnosis based on the individual pathologic presentations. The ICHD are further classified into primary versus secondary headaches. A primary headache is without a known underlying cause. The most common types of primary headaches include migraine, CHs, and TTHs. Secondary headaches are most often the result of another etiology, that is, inflammation, infection, trauma, vascular diseases, psychiatric disorders, and drugs ( Box 1 ). , A timely diagnostic workup is of the urgency if the patient’s clinical presentation is significant for a secondary headache. The latter aids in preventing a serious misdiagnosis because management strategies rely on time from initial presentation (see below). Painful cranial neuropathies that include other facial pains and other headaches comprise the third group of headaches classified by the ICHD (the reader is referred to references for further interest).

Box 1
Primary and secondary headache classification
Data from Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808.

  • Primary Headache Classification:

    • Migraine type

    • Tension type

    • Trigeminal autonomic hemicrania: cluster type and paroxysmal hemicrania

    • Other: unilateral neuralgiform type

    • Stimulus-induced headache: “ice-cream headache”

    • Thunderclap headache:

      • Primary; idiopathic

  • Secondary Headache Classification:

    • Trauma

    • Infection

    • Disorders of the sinus/teeth/eyes/ears/facial structures

    • Vasospasm/vascular diseases of the cranium

    • Withdrawal from substance abuse

    • Disorders that originate from psychiatric disease

    • Thunderclap headache: subarachnoid hemorrhages

    • Giant cell arteritis/Temporal arteritis

    • Medication overuse headache

Pathophysiologic mechanisms of headaches

Contemporary reviews define a headache as encompassing the entire head including the orofacial region. This evidence has important implications for the OMFS practitioner when patients present with orofacial symptoms. An example is a common neurovascular presentation of a “toothache” in patients with a history of migraine. , Neurovascular pain can arise in extracranial tissues via a pathway through the dental pulp, which is characterized as a “vascular toothache.” ,

All somatosensory information from craniovascular structures including nociceptive reflex arcs are relayed through anatomic connections of the trigeminovascular pain pathway, specifically through the trigeminal nucleus caudalis and its cervical extensions. Fig. 1 depicts pathways for innervation by the trigeminal sensory system. This complex network of reflex arcs function based on the properties of trigeminal afferents innervating distinct target tissues. Most are transmitted by somatic, motor, and autonomic nerve networks. These target tissue interactions with trigeminal neuron terminals contribute to the awareness and degree of pain perceived. Trigeminal pain conditions can arise from injury secondary to dental procedures, infection, neoplasia, or other diseases/dysfunction within the peripheral and/or central nervous system. Neurovascular disorders, such as primary headaches, can present as chronic orofacial pain, such as in the case of facial migraine, where the pain is localized in the second and third division of the trigeminal nerve. Cranial nerves 7, 9, and 10 also contribute to afferent input of the head and neck precipitating and/or exacerbating orofacial pain. Their afferent pathways converge on the trigeminal system at the level of the brainstem. This complex network can cause dilemmas in diagnosing the origin of pain. The clinician must differentiate heterotopic pain, source of pain not localized at the site of pain, or from referred pain; pain at one area that is supplied by afferents from another source of nociception. This explains why a patient may complain of shoulder and neck pain when describing intraoral pain. Examples of these pathways include peripheral connections, central and ascending connections, brainstem modulation, and hypothalamic modulation. All communicate with the trigeminovascular pain pathway via specific neuropeptides that contribute to autonomic, cognitive, endocrine, and affective symptoms. These pathways exhibit the pathology seen with headaches such as migraine and cluster types ( Box 2 and the reader is referred to reference 9 for an in-depth review of the physiologic mechanisms described earlier).

Fig. 1
Sagittal depiction of the trigeminovascular pathway for headache pain.

Box 2
Craniovascular nerve fibers and vasoactive neuropeptides in primary headaches
Adapted from Hoffmann J, Baca SM, Akerman S. Neurovascular mechanisms of migraine and cluster headache. J Cereb Blood Flow Metab. 2019 Apr;39(4):573-594.

Nerve Fiber Location Neuropeptide/Neurotransmitter
Trigeminal sensory nerve Calcitonin gene-related peptide
Substance P/Neurokinin A/Pituitary adenylate
Cyclase activating/Nitric oxide synthase
Parasympathetic fibers Vasoactive intestinal peptide
PACAP/Neuropeptide Y/Acetylcholine/Nitric
Sympathetic nerve fibers Noradrenaline/Neuropeptide Y/Adenosine triphosphate

Patient history and workup

Pain associated with a headache is a common presenting symptom seen every day and so the physical examination should include paradigms based on anatomic and physiologic correlations. The history of the present illness (HPI) will give the practitioner an accurate diagnosis 90% of the time, and therefore it is essential to allow the patient to describe his/her symptomatology. The common algorithm—chief complaint/HPI/medical history, physical examination, radiologic images, and a psychosocial profile—will facilitate ruling out certain pathology and hone in on specific patterns of pain onset. Other medical disorders, lifestyle features such as diet, caffeine, sleep habits, work, and personal stress provide useful risk predictors. Frequency of headache duration, location, triggering factors, severity, and alleviating features can lead to a well-thought-out differential and definitive diagnosis. The physical examination follows a generalized neurologic approach. Head and neck examination includes palpation of superficial scalp and other vessels of the head and neck, an orofacial examination that includes temporomandibular function, examination of the occlusion, bite, and an in-depth examination of the musculature for evidence of any myofascial pain dysfunction. The latter is most often associated with TTHs ( Box 3 ).

Box 3
Diagnostic elements in a history of headache
Adapted from Rizzoli P, Mullally WJ. Headache. Am J Med. 2018 Jan;131(1):17-24.

  • 1.

    Family history of primary and/or secondary headache symptoms

  • 2.

    Childhood symptoms of car sickness/Migraine symptoms/Gastrointestinal symptoms

  • 3.

    Features of an aura

  • 4.

    Comorbid diseases

  • 5.

    Age of onset of the first headache

  • 6.

    Therapies either prior or current to treat symptoms

  • 7.

    Lifestyle, ie, diet, drugs, alcohol, tobacco

  • 8.

    Frequency of headache events

Radiologic imaging can be a valuable adjunct depending on the HPI and associated “red flags,” that is, new-onset headache in geriatric patients, an abnormal neurologic examination with cranial nerve testing, associated systemic illness with fevers or stiff neck, “worst headache” of one’s life or first headache, headaches triggered by coughing, Valsalva upon exertion, and patients who suffer from immunocompromised disease states like HIV. Dodick (2003) introduced the SNOOP mnemonic to characterize “red flags,” which may help distinguish primary and secondary headaches. , These criteria were further revised and adapted to the emergency room setting by Nye and Ward to include systemic illness (eg, fever, chills, human immunodeficiency virus, history of cancer), neurologic signs (eg, change in mental status, asymmetric reflexes), onset (eg, acute, sudden or split second thunderclap headache), older patients (eg, >50 years with new or progressive headache), previous headache history (eg, first headache or different headache changing in frequency, severity, or clinical features), headache in children younger than 5 years, and headache worsening under observation. Some investigators also use an additional expression entitled “yellow flags.”

The application of neuroimaging to diagnose the aforementioned diseases can be costly and there have been several studies that report a low rate of identifiable intracranial pathology in patients presenting with headaches. A retrospective review by Ifediora examined the rate of intracranial findings following imaging of headache symptomatology over a 7-year period in a catchment of patients seen at a general practice medicine clinic. All forms of headaches and migraines with variations were examined with a mean patient age of 38 years and no gender predilection. This study concluded that regardless of imaging type, that is, CT or MRI, positive intracranial findings were uncommon following imaging. Larger studies, however, are needed especially when comorbidities of psychological disease are also present to validate the findings in this study. Several national and international guidelines exist and most agree that neuroimaging is usually not indicated in patients with a normal neurologic examination in the setting of migraine, CH, and TTH presentation.

Pharmacologic management of headaches by prescription

Pharmacologic therapy of headaches is most often based on the severity of symptoms and the degree of disability experienced by the patient. The practitioner must be judicious in his/her approach because drug therapy forms a part of an overall algorithm in patient management. Triggers of headache onset are often precipitated by lifestyle issues such as sleep patterns, inadequate hydration, and stress. Correction of these risk predictors can avoid the need for medication, especially in patients who suffer from TTHs. The latter may also be treated by over-the-counter (OTC) medications (see below). Drug therapy, however, can become the mainstay for the treatment of headaches based on the principles of proper diagnosis and subsequent effective choices of medication. The use of prescription medication, as such, is predicated upon whether its use will be abortive during an acute attack or preventive to reduce the frequency and severity of attacks. This preventive therapy can also decrease or avoid medication overuse headaches (MOHs; see below).

Acute and preventive medications have a broad spectrum of effect, and are specific to particular types of headaches. Abortive (acute) is often administered when symptomatology is mild and often is used in combination with antinausea medications. There is, however, a high potential for medication overuse (see below). Preventive treatment reduces severity, frequency, and avoids medication overuse and is often the treatment applied in patients whose attacks result in disability lasting 3 days or more, patients where acute therapy may be contraindicated or when there exists a combination of headache presentation, that is, hemiplegic migraine or CHs. The latter may require both abortive and preventive therapy.

The following sections focus on current prescription medications for the treatment of acute and chronic headaches (HA). The main types of headaches include migraine, cluster, and tension-type headaches. Each headache type described will aid the provider in determining the proper medications that are evidence-based such as triptans and ergotamine derivatives, as well as OTC medications. The following common primary headache disorders are presented with respect to pharmacologic and nonpharmacologic management. Fig. 2 provides an algorithm to guide the provider in determining the type of medication(s).

Fig. 2
Algorithm for the type of headache and medication choices.


Migraine is a common primary headache that affects 10% to 12% of the adult population; 6% of men and 18% of women that peaks between ages 35 and 45 years. The cost of treatment can exceed 19.6 billion dollars per year , Symptomatology is preceded by triggers such as stress, foods, loss of sleep, and menstruation. Clinical presentation is separated into 4 phases: (1) prodromal, (2) an aura or without aura, (3) the actual headache, and (4) postdrome phase. , , A careful differential diagnosis includes tension headache, orodental pain, other vascular disorders, and intracranial tumors. Although the pathophysiology is not completely clear, it originates from the trigeminovascular system that receives nociceptive afferents from the dura, meningeal blood vessels, and innervation from V1. Cervical innervation also forms part of this network and migraines pain is most often referred to the neck. These afferents cause release of inflammatory mediators (substance P, calcitonin-gene-related peptide, and neurokinins; see Box 2 ) that facilitate the pain transmission. ,

The therapeutic interventions of migraine headaches are either nonpharmacologic (biofeedback, hypnosis, and psychological therapies) or pharmacologic and are predicated upon whether the migraine has an aura phase (A) or not (WA). , Facial migraines (WA) present with a typical migraine that is localized to the face and is unilateral, associated with nausea, phonophobia, and photophobia. Once diagnosed, pharmacologic treatment can be either abortive or preventive based on the timeline of the headache symptomatology. Migraines that occur less than 2 times/mo can be treated with abortive medications, whereas those that occur more frequently need preventive therapy.

Abortive medications

Box 4 lists the pharmacologic abortive agents by type and mechanism of action. Abortive treatment is for acute symptomatic events as well as supplemental therapy for preventive medications during a migraine event. Nonsteroidal anti-inflammatory drugs (NSAIDS) and selective COX-2 inhibitors—naproxen sodium, ibuprofen, and rofecoxib—are effective but not over an extended daily regimen due to adverse systemic effects. , Ergotamine derivatives (DHE) have been quite effective for severe acute migraine episodes because of their significant effect on vasoconstriction of blood vessels. DHE can be administered intranasally, intravenously, and subcutaneously. ,

Box 4
Pharmacologic abortive agents based on type and mechanism of action

  • Triptans—5-HT1B and 5-HT1D serotonin receptor agonist

    • Includes alomtriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatruptan, and zolmitriptan

  • Ergot derivatives—5HT1 and 5HT2 serotonin receptor agonist

    • Ergotamine and dihydroergotamine

  • Midodrine—α1-receptor agonist

    • Midrin

    • FDA approval withdrawn in 2017, no longer in use

Drug Indication Dose Adverse effects
Sumatriptan (Imitrex) Migraine, cluster Oral: 25, 50, 100 mg capsule, maximum dose 200 mg in 24 h. Subcutaneous: 1–6 mg SC, maximum dose 12 mg in 24 h period, Intranasal: 5 mg, 10 mg, 20 mg, spray into one nostril, maximum dose 40 mg in 24 h period Coronary artery spasm
Dihydroergotamine (DHE) Migraine, cluster 1 mg IM/IV/SC, additional 1 mg dose given at hourly intervals as needed, maximum daily dose: IV; 2 mg/24 h, IM/SC 3 mg over 24 h Nausea/Vomiting
Only gold members can continue reading. Log In or Register to continue

Stay updated, free dental videos. Join our Telegram channel

Aug 14, 2022 | Posted by in Oral and Maxillofacial Surgery | Comments Off on An Update on Diagnosis and Pharmacologic Therapy for Headache in the Oral and Maxillofacial Surgery Practice

VIDEdental - Online dental courses

Get VIDEdental app for watching clinical videos