Migraine isn't always just a headache. This comprehensive review explores a fascinating and often-misunderstood condition called orofacial migraine, where migraine pain occurs in the face, jaw, or teeth instead of (or in addition to) the head. The authors, Drs. Rafael Benoliel and Arne May, explain that this condition is frequently misdiagnosed as sinusitis or dental problems, leading to unnecessary dental procedures and delayed treatment. The article also covers a related condition called neurovascular orofacial pain (NVOP), which shares many features with migraine but has its own distinct characteristics. Understanding these conditions is crucial because they affect an estimated 1% of the population and can cause significant suffering when left unrecognized.
Migraine is one of the most common neurological conditions worldwide, affecting millions of people. The two most common types are migraine without aura and migraine with aura. The diagnosis of migraine is based on clear criteria outlined in the International Classification of Headache Disorders version 3 (ICHD-3).
Here's something surprising: the ICHD-3 criteria don't specify where the pain must be located. This is different from how other primary headaches are classified, and it reflects the fact that migraine pain can occur in many different locations.
While most people think of migraine as a headache, there are increasing reports of migraine pain occurring in the facial region. These facial presentations of migraine aren't easy to diagnose because they appear in the lower two-thirds of the face, often in the maxillary sinus region (the area behind your cheekbones), around the ear, in the upper or lower jaws, and in the teeth. The symptoms often resemble sinusitis (sinus infection) or dental pathology, which creates significant diagnostic challenges.
In 2024, the International Classification of Orofacial Pain (ICOP) was published, which finally bridged the classification gap for various orofacial pains not included in the ICHD-3. Section 5 of the ICOP specifically deals with orofacial presentations of primary headaches, clearly classifying orofacial presentations of primary migraine and neurovascular orofacial pains.
The ICOP isn't just a classification system—it's also a bridge between the intimately related subjects of oral, face, and head pain. In clinical practice, doctors see three types of patients who typify the overlap between headache and orofacial pain:
The ICOP classification system includes several categories of orofacial pain that resemble primary headaches. These include orofacial migraine (both episodic and chronic forms), tension-type orofacial pain, trigeminal autonomic orofacial pain (including cluster orofacial attacks, paroxysmal hemifacial pain, and short-lasting unilateral neuralgiform facial pain attacks with cranial autonomic symptoms), and neurovascular orofacial pain (both short-lasting and long-lasting forms).
Several reports have documented migraine-like pain in the lower two-thirds of the face. However, there were no clear and consistent criteria for diagnosis, and different terms were assigned, such as orofacial migraine, lower-half migraine, migraine with isolated facial pain, or migraine presenting as isolated facial pain.
This phenomenon isn't new. In 1963, a physician named Woolf wrote: "The sites of migraine headache are notably temporal, supraorbital, frontal, retrobulbar, parietal, auricular, and occipital. However... they may occur as well in the malar region, the upper and lower teeth, at the base of the nose, in the median wall of the orbit, in the neck." Given this long-standing recognition, it's surprising that this presentation has caused so many diagnostic difficulties.
The ICHD-3 footnotes for migraine state: "a subset of otherwise typical patients has facial location of pain, which is called 'facial migraine' in the literature; there is no evidence that these patients form a separate subgroup of migraine patients."
Clinical experience confirms this and further suggests that in addition to an orofacial component in migraine attacks, orofacial migraine can be completely isolated from head pain. Often, these isolated facial pains present with a clinical picture that, other than the location, may be diagnosed as migraine. The unusual location often leads to erroneous diagnoses such as oral pathology or sinusitis.
Interestingly, patients with self-reported sinusitis who actually have migraine pain will respond well to sumatriptan (a migraine medication). This suggests that many cases of "sinusitis" may actually be undiagnosed migraine.
There is limited data on how common orofacial migraine is. Based on existing literature, the authors estimate a prevalence of about 1% of the population.
A population-based study of migraine patients showed that while orofacial migraine wasn't unusual in migraine patients (8.9% had it), isolated orofacial migraine (without any head pain) was exceptionally rare (0.2%). However, this study had limitations—the screening questions only studied migraine sufferers and which ones reported additional orofacial migraine. Patients with isolated orofacial migraine without concomitant or prominent symptoms would have been excluded.
Another study of 1,176 patients with migraine found 58 with isolated orofacial migraine. The cohort in that study seems mixed, with both orofacial migraine and neurovascular orofacial pain patients. Pain location was restricted to intra-oral and/or extra-oral areas. Notably, two-thirds of these patients underwent endodontics (root canals) or multiple tooth extractions, and around 45% had cranial autonomic symptoms (CASs)—symptoms like tearing, eye redness, or nasal congestion that occur on the same side as the pain.
In a recent study including 1,983 migraine patients, 44 had a facial component (2.3%). Only one patient had a totally isolated orofacial migraine, and five had a "relocated" migraine (meaning their headache had been replaced by facial pain). The rest (n=38) had ongoing migraine with an orofacial component. The most common facial involvement was in the maxilla (upper jaw), often involving dental pain. The mandible (lower jaw) was affected in only four cases of facial involvement (9.3%).
Location and Severity. The vast majority of patients report moderate-to-severe unilateral (one-sided) pain. Pain occurs primarily in the midface and may resemble sinusitis. It may also appear in the lower face, over the mandible (jawbone).
Quality and Temporal Pattern. Pain is usually throbbing and mimics inflammatory conditions of the maxillary sinuses and teeth. One would assume that the duration is the same as in migraine (4-72 hours untreated), but the variability hasn't been well described. Although migraine is typically episodic, there are case series showing a chronic course—up to 66% in one study.
Accompanying Phenomena. Research has shown that patients with isolated orofacial migraine report significantly more cranial autonomic symptoms (CASs), including:
These symptoms occurred in 47.8% of orofacial migraine patients compared to only 7.9% of other migraine patients—a striking difference. No aura has been reported in orofacial migraine at this point.
Treatment Response. Migraine therapy should be effective in orofacial migraine, but researchers are still lacking data on this.
Differential Diagnosis. Orofacial migraine is not a straightforward diagnosis and is often masked by its atypical location and features. It may mimic facial forms of cluster headache and a number of atypical facial pains. Confusion with sinusitis and dental pain is common.
The ICOP defines orofacial pains resembling presentations of primary neurovascular headaches under three categories: orofacial migraine, orofacial trigeminal autonomic cephalalgias (TACs), and neurovascular orofacial pain (NVOP). NVOP is subdivided into short-lasting and long-lasting forms.
NVOP shares many migraine signs and symptoms, such as a pulsating quality, often accompanied by nausea and/or vomiting, photophobia (sensitivity to light), and phonophobia (sensitivity to sound). Additionally, NVOP includes signs and symptoms such as toothache and dental sensitivity to cold, while cranial autonomic symptoms include ipsilateral lacrimation (tearing on the same side) and/or conjunctival injection and ipsilateral rhinorrhea (runny nose) and/or nasal congestion.
The clinical data suggest that NVOP includes Type 2 and Type 3 patients who develop migraine-like pain as described earlier. In some cases, a dental intervention such as tooth extraction may result in the "remapping" of an isolated orofacial migraine-type pain at the site of intervention. It should also be noted that in some Type 1 cases (facial pain during a migraine attack), toothache in the same-side area is a common complaint.
The onset of NVOP is typically around 40-50 years of age (mean 43.4 years), with a female-to-male ratio approaching 4:1. Time to diagnosis ranged from 1 to 528 months, indicating significant diagnostic difficulties. In up to two-thirds of cases, the pain was diagnosed as dental pathology, and patients underwent unwarranted dental interventions.
To date, over 199 cases have been published establishing a demographic and clinical database.
Location. Pain is overwhelmingly unilateral (76%). Pain occurs mostly intraorally, involving the teeth and the alveolar process (the bone that holds teeth) in 62% of cases. Mucosal sites are less often affected by pain (32%). Pain referral is roughly one-third to each of the following areas: perioral structures (lips, chin, etc.), the periorbital region (usually infraorbital, below the eye), and the preauricular region (in front of the ear).
Quality and Temporal Pattern. Severe, pulsating pain (rated 7-8 on a 10-point Visual Analog Scale) lasts from minutes to hours and up to 3 days. Most cases are characterized by a high frequency of attacks of short duration (60%), exacerbated by cold food ingestion. NVOP is subdivided into short-lasting and long-lasting (40%) forms. Both are mostly recurrent and chronic in nature.
Accompanying Phenomena. The majority of patients (80%) reported cranial autonomic symptoms, specifically:
Photo/phonophobia (14%) and nausea (24%) may also be present. Very often, patients report dental hypersensitivity to cold, leading to diagnostic confusion with dental pathology.
Low-dose amitriptyline (an antidepressant often used for pain), propranolol (a beta-blocker), and anti-convulsant therapy have been successful preventive treatments in NVOP patients. Triptans (migraine abortive medications) were reported in one study and were effective in all patients. Due to the persistent pattern and the exquisite sensitivity to cold food ingestion, preventive pharmacological treatment is preferable in NVOP.
Because of the dental thermal hypersensitivity observed in NVOP, the differential diagnosis includes dental pulpitis (tooth nerve inflammation) and cold-stimulus (or "ice-cream") headache. Although initially dental pulpitis may resemble NVOP, careful history and examination will differentiate them. A trial of triptan treatment may be considered to confirm or refute migraine-like mechanisms in NVOP.
Cold-stimulus headache occurs particularly in individuals with a history of migraine and is not associated with dental pathology. Pain is evoked by cold material stimulating the palate and posterior pharyngeal wall. The evoked facial pain is in the mid-frontal region or around the ears, referred probably by the trigeminal and glossopharyngeal nerves. No treatment other than sensible caution is needed.
Post-traumatic trigeminal neuropathy (PTTN) may be confused with NVOP due to the prolonged gingival (gum) cold allodynia (pain from a normally non-painful stimulus) that often accompanies PTTN. However, PTTN's history of trauma, the sensory deficits on examination, and the pain quality and pattern are very different from those of NVOP.
NVOP vs. Orofacial Migraine. NVOP and orofacial migraine show great similarity, particularly their response to preventive pharmacological treatment. In a recent study, researchers found that these entities were similar in age, sex distribution, and pain intensity. However, orofacial migraine patients presented with more cranial autonomic symptoms, more migraine symptoms (nausea, photophobia), and significantly more pain-related awakening from sleep. Orofacial migraine pain was more frequently associated with headache. NVOP patients have, by definition, pain that mimics toothache, which is rare in orofacial migraine.
In summary, the diagnostic features of orofacial migraine and NVOP indicate that there are many similarities between the two. However, unique features suggest that orofacial migraine and NVOP remain distinct diagnostic entities, in accordance with the ICOP. This is important for both clinical and research purposes.
Migraine headache reflects an altered brain excitability state that can activate the system in genetically susceptible individuals. The hypothalamus and its functional connections to brainstem nuclei and cortical regions underlie the premonitory phase (the early warning signs before the pain starts), whereas the headache phase involves increased sensory processing within peripheral and central trigeminovascular (TMV) pathways.
Current data indicate that cortical spreading depolarization (a wave of electrical activity that spreads across the brain) and activation of the TMV system and its constituent neuropeptides (resulting in neurogenic inflammation), as well as neuronal and glial ion channels and transporters, contribute to the putative cortical excitatory/inhibitory imbalance that makes those with migraine susceptible to an attack.
The various symptoms and neurological disturbances observed during all phases of migraine are complex and wide-ranging. Disturbances of sensory function, sensory affect, cognitive and autonomic function may be experienced, suggesting the involvement of multiple neural networks.
The mechanisms underlying facial pain presentations of neurovascular headache disorders are suspected to involve the mechanisms described above but remain unclear. A common hypothesis implicates innervation patterns of the intracranial and extracranial trigeminal nerve.
The dura mater (the tough outer layer of the membranes surrounding the brain) is a pain-sensitive intracranial structure and is primarily innervated by the V1 branch (the ophthalmic branch) of the trigeminal nerve, with little arising from V2 and V3 (the maxillary and mandibular branches). The intra- and extracranial innervations of the trigeminal nerve communicate the presence of pain. Intracranial fibers exit the skull to innervate the periosteum (the membrane covering bones) and extracranial tissues, such as the pericranial muscles (muscles around the skull).
This connection provides a route for how TMV activation of the dura extends to the extracranial counterpart—the V1 dermatome in the face. In the posterior cranium, the dura is innervated by intracranial fibers from V2, V3, and cervical (neck) branches. Their activation is more likely to cause posterior head pain. Activation of intracranial V1 would evoke frontal headache.
Neurogenic inflammation induced by intranasal administration of capsaicin (the active component in chili peppers) and formalin increased plasma protein extravasation (leakage of fluid from blood vessels) not only in the nasal mucosa but also in the dura mater. Thus, extracranial activation of the trigeminal nerves leads to intracranial activation of their counterparts.
Based on the anatomical and functional connection between different branches of the trigeminal system, facial presentations of headache should be more prevalent. Migraine in the lower two-thirds of the face accompanied by systemic and cranial autonomic symptoms raises mechanistic challenges. The pathophysiology of NVOP may be based on migraine. If so, researchers need to analyze the possibility that neurogenic inflammation occurs in the oral and perioral tissues and consider its possible role in the phenotype of NVOP.
The dental pulp (the innermost part of the tooth containing nerves and blood vessels) is innervated by unmyelinated C-fibers, autonomic nerves, and myelinated A-δ and A-β fibers. Also present in the dental pulp and oral mucosa in several species including humans are SP- and CGRP-positive immunoreactive fibers (substance P and calcitonin gene-related peptide, both involved in pain signaling).
The levels of two sensory neuropeptides (SP and CGRP) and two endogenous opioids (methionine-enkephalin and β-endorphin) were studied in human dental pulps. After 24 hours of an intrusive stimulus associated with discomfort, only SP significantly increased, clarifying the role of neurogenic inflammation in early injury response.
The human dental pulp has high expression of CGRP, SP, and VIP (vasoactive intestinal peptide), and this expression is higher in permanent teeth than in deciduous (baby) teeth. This possibly explains the lack of NVOP reported in children. Antidromic electrical nerve stimulation (stimulation that goes in the opposite direction of normal nerve signaling) induces neurogenic inflammation in the dental pulp of dogs and in the dental pulp, lower lip, and oral mucosa of rats, which reduces after sympathectomy (surgical removal of sympathetic nerves). Possible collateral C-fiber innervation in the same quadrant may explain the symptomatology in adjacent teeth. This phenomenon may underlie the referral patterns in primary NVOP. The anatomical substrate for neurovascular tooth pain is therefore present.
Neurogenic inflammation in the TMV system seems to play a central role in the genesis of headache and facial pain, so the same mechanism could function in the oral mucosa and teeth.
Activation of 5-HT-1B/1D receptors (serotonin receptors), through local injection of naratriptan (a triptan medication) into the ventrolateral PAG (periaqueductal gray, a brain region involved in pain modulation), produces selective inhibition of TMV nociceptive afferent input but not facial afferents. It is possible that this finding underlies the sparse reports of successful treatment of orofacial neurovascular counterparts (orofacial migraine, NVOP, and TACs).
The central somatotopy (the mapping of body parts in the brain) is onion-ring shaped, with the center being the perioral region (around the mouth). However, fibers from the V1 branch project more to the caudal (lower) part of the trigeminal nucleus caudalis (TNC), whereas those from the V2 and V3 branches project more to the rostral (upper) part of the TNC.
This distribution also provides the anatomical basis for why cervical modulation, such as greater occipital nerve block (an injection of anesthetic near the back of the head), may be effective in aborting headache disorders, since the V1 dermatome projects to the most caudal part of the TNC and is located directly adjacent to the secondary sensory neurons of the C2/C3 branches in the spinal cord.
Capsaicin stimulation of the V1 dermatome modulated the pain threshold in the V2, V3, and greater occipital nerve dermatomes. Stimulation at the greater occipital nerve was able to change the pain threshold on all three branches of the trigeminal nerve, but with a stronger effect on V1 compared to V2/V3. Thus, functional interactions between different branches of the trigeminal nerve take place at the pontomedullary level (in the brainstem).
There is a functional connection between the limbic system (the brain's emotional center) and the ophthalmic branch. This functional connection explains why such attack-like pain in migraine is predominantly in the ophthalmic dermatome (the forehead area). Following this thought, the facial presentations would be a simple "spread" of pontomedullary activation in Type 1 and Type 2 facial presentations of headache, whereas the isolated facial attacks resembling headaches (Type 3) are due to rare functional connections between the limbic system and the maxillary or mandibular brainstem nuclei. Further studies into this subject are needed.
This review article has several important limitations that patients should understand:
If you experience facial pain that might be orofacial migraine or NVOP, here are some important recommendations:
Orofacial migraine is a type of migraine where pain occurs in the face, jaw, or teeth instead of or in addition to the head. It is often misdiagnosed as sinusitis or dental problems. The pain is typically throbbing, one-sided, and may be accompanied by nausea, light sensitivity, or autonomic symptoms like tearing or nasal congestion.
Based on existing literature, the estimated prevalence of orofacial migraine is about 1% of the population. In a population-based study, 8.9% of migraine patients had orofacial migraine, but isolated orofacial migraine without any head pain was very rare, occurring in only 0.2% of migraine patients.
Symptoms include moderate-to-severe one-sided pain in the midface, upper jaw, or teeth, often throbbing and resembling sinusitis or dental pain. Attacks may last 4-72 hours. Many patients also experience cranial autonomic symptoms like eye redness, tearing, nasal congestion, or drooping eyelid. No aura has been reported.
NVOP is a related condition that mimics toothache and shares migraine features like pulsating pain, nausea, and sensitivity to light or sound. It often includes dental sensitivity to cold and autonomic symptoms like tearing or nasal congestion. NVOP can be short-lasting or long-lasting and is frequently misdiagnosed as dental pathology.
Because the pain is located in the face, jaw, or teeth, it is commonly mistaken for sinusitis or dental problems. Up to two-thirds of NVOP patients undergo unnecessary dental procedures like root canals or tooth extractions. The unusual location leads to delayed diagnosis and treatment.
Migraine therapies, including triptans, may be effective. For NVOP, preventive treatments such as low-dose amitriptyline, propranolol, or anti-convulsant medications have been successful. In one study, triptans were effective in all NVOP patients treated. Preventive medication is often preferred due to the persistent pattern and cold sensitivity.
Consider migraine as a possible cause if you have throbbing, one-sided facial pain with nausea, light sensitivity, or autonomic symptoms. Seek evaluation from a headache specialist, orofacial pain specialist, or neurologist. Be cautious about dental procedures; get a second opinion if imaging is normal. Keep a pain diary and discuss preventive treatment and triptans with your doctor.
Original Article: "Orofacial Migraine—A Narrative Review"
Authors: Rafael Benoliel and Arne May
Journal: Journal of Clinical Medicine, 2024, Volume 13, Article 5745
Publication Date: September 26, 2024
DOI: 10.3390/jcm13195745
This patient-friendly article is based on peer-reviewed research. It has been adapted to make the scientific content more accessible to patients and the general public while preserving all key data, findings, and conclusions from the original publication.
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