Facial presentations of primary headache disorders

Abstract

Background

Many patients with mid-face or lower face craniofacial pain are diagnosed, based on accompanying signs and symptoms and features other than location, as either atypical migraines or atypical TACs. Distinguishing features of headache disorders as a cause of facial pain include the temporal pattern of pain, associated symptoms including light and sound sensitivity and nausea, cranial autonomic symptoms, and the lack of local triggering among others.

Results

An intraoral neurovascular pain has been observed, and was termed neurovascular orofacial pain (NVOP). Due to its location, and signs imitating dental pulpitis, it has great diagnostic and therapeutic importance for differentiating NVOP from dental pathology. The hypothesized mechanism is neurogenic inflammatory activation within the space confined by dentine around the dental pulp, expressed in strong paroxysmal pain and typical allodynia to cold foods.

Conclusion

Facial manifestations of headache disorders and primary facial pain disorders share common trigeminal nerve input, yet they are highly distinct disorders. Somatotopic segregation may occur at the level of the trigeminal nucleus, thalamus, and somatosensory cortex, and distinct ionic or neurochemical signaling pathways may be involved. Further investigation of facial presentations of headache disorders has the potential to provide new insight into the interface between headache and facial pain.

Definition

The term neurovascular headache reflects the suspected etiology of the pain, which is considered to result, at least partly, from an interaction between the nervous and vascular systems (1). Although sharing common pathophysiological pathways of activation of the trigeminal vascular system, neurovascular craniofacial pains are clearly classified based on well-defined criteria of location, attack frequency, duration, accompanying signs or symptoms, and treatment response. Primary headache disorders typically affect the frontal, temporal, parietal, or occipital regions of the head, and may also include neck pain in a significant proportion of patients. In some cases, however, migraine head pain extends to the mid face or lower half of the face or occurs there without affecting the head (2,3). The terms “lower facial migraine”, or “neurovascular orofacial pain” have been used by different authors to describe this atypical pain location (4). Facial presentations of headache disorders are often misdiagnosed, and many times mistreated as dental or nasal problems (5). The International Classification of Headache Disorders defines migraine as a headache with associated symptoms including light and sound sensitivity and nausea. Although unilateral location is one of the defining features of the pain, the classification does not otherwise specify the location of the pain (6). In migraine, the pain may occur in any region of the head, face or the neck, and may vary considerably from patient to patient and from attack to attack in a given patient. Cluster headache is strictly hemicranial and typically affects the orbital region, or less frequently the temporal regions, with accompanying unilateral cranial autonomic symptoms.

Symptomatology and epidemiology

There are cases of migraine in which pain extends to, or even more rarely, is solely located in the face. These conditions are challenging, as associated migraine symptoms often remain unrecognized. While pain in the maxillary or mandibular regions may be related to sinus or dental pathology, temporomandibular disorders, or trigeminal neuralgia or neuropathy, the clinical features and examination findings with these disorders help to distinguish them from migraine.

Facial pain in migraine can be subdivided into two categories in which a) migraine head pain is located predominantly in the head and extends to the lower facial region, and b) migraine pain occurs only in the lower face without affecting the head.

The first category is much more frequent. A population-based study investigated a sample of 517 people with migraine and found that in 46 cases (8.9%), migraine pain was focused in the head but extended to the lower half of the face (7).

Another case – facial pain in migraine without headache – is rarer. Lance mentioned lower half headache under the vascular headache of migraine type to separate this group from atypical facial pain (8). Additionally, 6% of 973 patients in a head and neck practice setting described migraine-associated pain isolated to the second trigeminal division (9), and of 100 patients with “sinus headache”, 85% had migraine or probable migraine and 1.6% reported pain confined to the second trigeminal division (10).

Facial pain in cluster headache is also rare but possible. Bahra and Goadsby reported that almost every second cluster headache patient has been seen by a dentist, and that one in five patients erroneously underwent dental treatment (11). Ekbom et al. (12) differentiated an “upper syndrome” and a “lower syndrome” cluster headache, with maximal pain around and below the eye, respectively; the latter was a facial pain syndrome.

Only one patient was identified by Yoon et al. with isolated facial migraine. However, they admitted that this low rate could be due to a biased sampling; and those “having isolated facial pain without any other migraine symptoms could have been neglected” (7).

In1997 Benoliel et al. (13) reported on 55 patients with neurovascular facial pain; 29 patients (53%) presented primary intraoral pain with characteristics of isolated neurovascular craniofacial pain. Based on location and unique characteristics and features, not fitting any of the IHS classifications, they termed the latter “neurovascular orofacial pain” (NVOP). The average age of NVOP patients was 42.6 years. Peñarrocha et al. (14) identified 11 patients with lower-half migraine, mean age 35 years. Obermann et al. (15) studied a cohort of seven patients, mean age 55.4. Recently, an additional 61 patients with NVOP were studied (unpublished data), mean age 40.3. Based on a total of 131 NVOP patients, summarized from the above, the mean age was 40.9 and the female to male ratio was 3.2:1.These data point to a possible later onset age of facial neurovascular pain than in migraine; 50% of patients have migraine before the age of 25, and by 35 years 75% are affected (16), with a female to male ratio of 2:1 (17,18).

In addition to an atypical location, NVOP’s clinical features contain a distinctive combination of signs and symptoms common to both migraine and TACs. Also, due to its intraoral location, it has unique signs imitating dental pulpitis (such as strong, short paroxysmal pain associated with the consumption of cold or hot food); the migraine and TAC-like features have great diagnostic and therapeutic importance for differentiating NVOP from dental pathology (5,13,19,20).

Thus, neurovascular orofacial pain (NVOP) may form a distinct sub-diagnosis of migraine and deserves careful examination. Often, patients report dental hypersensitivity to cold leading to diagnostic confusion (5,20). While teeth may be over-reacting to clinical tests (e.g. cold application), similarly to teeth with pulpitis, the inflammatory process is assumed to be neurogenic rather than locally infective. Clinicians should be very attentive to the patient’s complaint and the lack of local dental pathology that would explain such symptomatology. Pain can be accompanied by various local autonomic signs, specifically tearing (10%), nasal congestion (7%), a feeling of swelling or fullness (7%), particularly in the cheek, and a complaint of excessive sweating (7%) were reported (13). Other phenomena such as photo- or phonophobia (14%) and nausea (24%) are observed (13–15). These are similar to other patients with neurovascular facial pain, who suffer more trigemino-autonomic symptoms than migraine patients with no facial distribution (47.8% vs. 7.9%, p < 0.001) (7). Although the term “lower-half migraine” has historical value (14), it is suggested that when pain occurs in the dental region, the term be updated to neurovascular orofacial pain (NVOP). There are enough differentiating factors to specifically classify NVOP as a distinctive form of migraine, discussed in detail by Sharav et al. (4). The most prominent are the oral and perioral location (9), a neurovascular “pulpitis” with unique pain characteristics (5,13–15,21) and a late age of onset. In addition, migraine is predominantly episodic while NVOP often emerges as chronic. However, while chronic migraine (CM) is mostly bilateral, chronic NVOP is mostly unilateral.

The similarities, in particular local autonomic signs, to the cluster headache (CH) group are limited by the fact that there is an overwhelming female preponderance and treatment response is not similar. Treatment of NVOP with classical antimigraine drugs has been successful, and firmly establishes an association with migraine (5,13–15). In chronic cases, very good results were observed with prophylactic propranolol, divalproex, or, when muscle tenderness is prominent, amitriptyline.

To conclude, although the head and face are intimately related, diagnostic classifications of headache and orofacial pain are not sufficiently integrated. The International Classification of Headache Disorders (ICHD) (6) has limited coverage of a number of currently accepted orofacial pain entities (19). Furthermore, the bibliography of this most recent edition (6), in its section on “Headache or facial pain …” is limited to references no later than 2001and needs updating.

The question regarding whether there is an advantage in giving different names, or definitions, to disease entities with a common etiological mechanism (i.e. neurovascular) in different locations (i.e. mid-face migraine, lower face migraine) remains controversial. We believe there is; different anatomical locations are associated with different clinical expressions (e.g. sinusitis, pulpitis) and many times deserve the diagnostic expertise and treatment by members of different specialties. Therefore, dentists, ENT and headache specialists need to cooperate in order to achieve the best treatment for these patients. Similarly, a group of pain disorders, associated with central neural dysfunction (e.g. fibromyalgia, irritable bowel syndrome or temporomandibular disorders), may fall within a category of similar disorders, yet each disorder clearly warrants a specific name or definition because of different anatomical locations and clinical expression.

Pathophysiology

The potential mechanisms underlying facial presentations of primary headache disorders remain largely speculative. Given that migraine and cluster headache, as well as other primary headaches, are commonly considered to be “trigeminovascular” pain syndromes, it is perhaps surprising that facial involvement of primary headache disorders is the exception rather than the rule. Since both headache disorders and facial pain disorders are presumed to share peripheral input through the trigeminal nerve, what are the mechanisms by which headache and facial pain remain such distinct disorders?

Anatomical considerations

The sensory innervation of intracranial and extracranial structures includes both trigeminal and cervical pathways (22). It has traditionally been assumed that one of the reasons for the distinction between headache and facial pain is the fact that the intracranial structures are predominantly innervated by branches of the first division of the trigeminal nerve (V1), whereas it is unusual for facial pain syndromes to occur in this distribution. However, dural innervation by the V2 and V3 branches has been clearly demonstrated (22), indicating that there is certainly overlap between dural and facial innervation at the level of trigeminal nerve branches as well as at the level of the trigeminal ganglion. Despite this overlap, it is possible that in most cases there is a strict somatotopic segregation of peripheral nerve fibers and cell bodies such that head pain and face pain remain distinct. Similar strict somatotopic segregation may occur at the level of the trigeminal nucleus, thalamus, and somatosensory cortex (23). In cases of primary headache disorders that present with facial pain, one hypothesis is that the normal somatotopic segregation between the cells transmitting pain from the head and face is disrupted either at the level of the trigeminal nerve or ganglion, or at central sites of convergence including the trigeminal nucleus, thalamus, or cortex. Another possibility is that anatomical variations including anastomoses between different nerves, or referred pain phenomena, could play a role. For example, anastomoses between the trigeminal and facial nerves, as well as between the facial nerve and branches of the upper cervical nerves, have been reported (24). This kind of anatomical variation could therefore represent a mechanism by which primary headache disorders could present as facial pain. The upper cervical nerve roots have been shown to extend branches to the region of the mandible in a majority of cadaveric specimens. Since stimulation of the upper cervical nerve roots has been shown to produce both head pain and orbital pain in different patterns in patients with and without migraine (25), it is possible that the C1–C3 nerves could play a role in cases in which primary headache disorders present with facial pain.

Cellular and neurochemical considerations

In addition to anatomical segregation of neuronal pathways of painful input from the head vs. face, there may also be distinct cellular and pharmacological signaling mechanisms of these pathways (26). In this regard, it is important to consider the clearly different responses of primary headache disorders, compared with facial pain disorders, to different therapies. Migraine and cluster headache consistently respond to triptans (5HT 1B, D, and F receptor agonists) as acute therapies, whereas with the exception of some isolated reports (27) these drugs typically have no benefit for trigeminal neuralgia. Similarly, indomethacin, which is an effective therapy for a number of trigeminal autonomic cephalalgias, is not typically effective as a therapy for trigeminal neuralgia. Conversely, carbamazepine, which is often effective as a therapy for trigeminal neuralgia, typically has no benefit as a preventive therapy for primary headache disorders. These differences in response to therapies indicate that there may be distinct ionic or neurochemical signaling pathways involved in the transmission of headache vs. facial pain.

Additionally, activation of 5-HT-1B/1D receptors, by local injection of naratriptan into ventrolateral PAG, produces selective inhibition of trigeminovascular nociceptive afferent input but not facial afferents (28). This finding points to the possible distinctiveness of orofacial neurovascular pain from migraine, and may have important consequences for the treatment of other neurovascular pains located in the orofacial region such as CH and NVOP. Thus, facial pain may be a symptom of primary headache disorders when nerves that transmit facial pain respond atypically to headache neurochemical triggers, or nerves that transmit headache pain respond to what are normally facial pain triggers.

Role of neurogenic inflammation

The pathophysiology of NVOP may be based on antidromic activation causing neurogenic inflammation (NI), similar to that which has been proposed in the past for migraine and/or CH. If so, we need to analyze the possibility that NI occurs in the oral and perioral tissues and consider its possible role in the phenotype of NVOP.

Nerve fibers exhibiting SP and CGRP-positive immunoreactivity are present in the dental pulp and oral mucosa in several species including humans (29). Following antidromic electrical nerve stimulation, neurogenic inflammation has been demonstrated in the dental pulp of dogs and in the dental pulp, lower lip and oral mucosa of rats (30,31). Hypothesized neurophysiological and neurochemical substrates for migraine and cluster headache are therefore also present in the tooth.

In the dental pulp, confinement by the surrounding dental hard tissues may lead to local build-up of pressure that contributes to intrapulpal nociceptor activation. For example, A-δ fibers have been shown to be sensitive to the increased intrapulpal pressure following plasma extravasation (32). However, homeostatic mechanisms limit pressure build up in the pulp following antidromic stimulation (33), probably by re-absorption into the circulation. This may explain clinical observations that in spite of pulpitis-like symptoms in the teeth of patients with NVOP, spontaneous pulp necrosis is rare.

Diagnostic considerations

Primary headache disorders should be considered as a cause of facial pain when the temporal characteristics of the pain and associated features are consistent with migraine or cluster headache. Associated nausea, light and sound sensitivity, and fatigue are significant signs that pain in the face is occurring as part of a primary headache disorder. Similarly, the presence of cranial autonomic features such as lacrimation, conjunctival injection, or rhinorrhea among others should prompt consideration of a primary headache disorder as opposed to a primary facial pain disorder. Given the unusual occurrence of facial pain as a manifestation of headache disorders, it is also important to consider a secondary cause of symptoms in these cases. Imaging of the head is reasonable to consider in unusual cases of a headache disorder presenting with facial pain. Additionally, due to the dental thermal hypersensitivity observed in NVOP, the differential diagnosis should include pulpitis. NVOP associated with strong cold allodynia of teeth is often not limited to one tooth only, and dental pathology (deep caries lesions or extensive restorations) is usually missing. Prolonged gingival cold allodynia should be considered in patients with atypical odontalgia (34). A trial of therapy with triptans should be considered in more complicated cases, and a positive response may have diagnostic value.

Treatment

If the diagnosis of acute facial pain is uncertain, treatment with a migraine and/or TAC-specific therapy may be warranted on a trial basis, especially if there are features suggestive of a primary headache disorder. Facial pain due to migraine or cluster headache may respond to triptans as acute therapy. A trial of inhaled oxygen as acute therapy may be warranted if the features of the attack are suggestive of cluster headache. Similarly, a trial of indomethacin may be warranted if there are features of paroxysmal hemicrania or hemicrania continua. Most patients with NVOP will need pharmacological management, either abortive or preventive. As many cases on NVOP are chronic in nature or, even when episodic, frequent, often daily, or evoked on cold food ingestion, the prophylactic approach is commonly warranted.

Prophylactic treatment guidelines for migraine were updated in 2012 (35), and serve well in the treatment of NVOP.

Questions/future directions

Questions regarding facial headache include:

What are the mechanisms by which head pain is distinguished from facial pain?

If both primary headache disorders and facial pain disorders are trigeminal pain disorders, why is their response to therapies so different?

Structural and functional imaging studies have the potential to provide new information regarding these questions, and have the potential to identify peripheral and central regions that are differentially activated in patients with facial neurovascular pain, as compared with those with typical migraine headache. The development of new therapies for migraine and cluster headache also represents an opportunity to investigate these questions. Novel therapeutic approaches for migraine that target neuropeptides such as CGRP and PACAP should be investigated for facial pain disorders. Investigations of facial presentations of primary headache disorders have the potential to provide new insight into the interface between headache and facial pain.

Clinical implications

Structural and functional imaging studies have the potential to provide new information about the mechanisms of head pain vs. facial pain.