19 Craniofacial pain

Craniofacial pain, excluding the headache disorders, comprises a heterogeneous group of conditions. Some fall within the sphere of the neurologist, but many call for other specialist skills in diagnosis and management. The site of pain is not always a good guide to either the nature of the pain or the tissue of origin. Patients with craniofacial pain are frequently referred to the neurologist on an assumption that the pain is neuralgic, and for this reason neurologists need to be aware of the many potential causes and be prepared to collaborate closely with other specialists, including the ear, nose, and throat surgeon, ophthalmologist, dental surgeon, oral medicine physician, and psychiatrist. An accurate and detailed history is essential, because in many patients with facial pain, there will be no abnormal physical signs and the diagnosis rests entirely on the history. The causes of craniofacial pain are listed in Table 19.1, in a classification partly anatomical and partly pathological.

The somatosensory innervation of craniofacial structures is through the sensory components of the trigeminal, facial, glossopharyngeal, and vagus nerves, and the upper cervical roots, C2 and C3. The trigeminal innervation is extensive, involving deep tissues as well as skin (Table 19.2). Pathological processes affecting non-cutaneous tissues innervated by the trigeminal nerve can cause pain that is localized to the affected area, or diffuse pain radiating onto the face, leading to diagnostic difficulty. However, processes affecting trigeminal innervated structures cause facial pain that is usually experienced within the confines of trigeminal territory. Furthermore, with a few exceptions, facial pain with a serious underlying cause, calling for neurological or other investigations, is nearly always strictly unilateral. Pain that extends beyond trigeminal territory or is bilateral is much less likely to have an underlying neurological basis.

Accurate diagnosis of craniofacial pain can be either very straightforward or extremely challenging; liaison with specialists in the relevant fields listed above is frequently advisable. The neurologist must be aware of the broad range of causes of craniofacial pain, should take a comprehensive and detailed history, and perform a careful physical examination. The examination should include not only a full neurological assessment, but additionally, depending on the context and distribution of symptoms, the following may also require assessment:

In patients presenting with localized cranial pain posterior to the trigeminal territory, scalp tenderness, movements of the cervical spine, and posterior nuchal muscle tenderness should be assessed. The many causes of craniofacial pain (Table 19.1) emphasize the importance of such a broad and comprehensive approach to examination.

Trigeminal neuralgia, or tic douloureux, has unique and distinctive characteristics. It is pain of abrupt onset, occurring unilaterally in severe brief paroxysms, in the distribution of one or more branches of the trigeminal nerve (Section 20.2.4). In the great majority of patients there are no physical signs and the diagnosis rests entirely on an accurate history. There is a tendency for trigeminal neuralgia to be over-diagnosed, as a result of failure to recognize and apply the strict clinical criteria for the diagnosis. Erroneous diagnosis has major implications for treatment, leading potentially to unsuitable medical and worse still, surgical treatment.

Trigeminal neuralgia is sometimes referred to as ‘idiopathic trigeminal neuralgia’, but as described below, there is now good evidence from imaging, surgical, and pathological studies that subtle vascular compression can be demonstrated or inferred in the majority of patients.

‘Symptomatic trigeminal neuralgia’. This refers to clinically indistinguishable pain which is shown to be due to structural lesions of the trigeminal root other than subtle vascular compression, such as tumours and arteriovenous malformations. In fact, it is rare for lesions of this type to cause neuralgia which truly has the characteristics of ‘idiopathic’ trigeminal neuralgia, and there are frequently other clues to the presence of a gross lesion in patients with ‘symptomatic’ trigeminal neuralgia, in particular facial sensory loss. Trigeminal neuralgia also occurs in multiple sclerosis. In this setting, in the early stages, pain is often indistinguishable from ‘idiopathic’ neuralgia, but tends to occur in younger patients, to change over time, and responds progressively less well to treatment.

‘Atypical trigeminal neuralgia’ is a term sometimes used to describe pain that has some but not all the characteristic features of the condition. However, although there may be unusual or additional features in some patients, one should guard against making a diagnosis of trigeminal neuralgia on inadequate grounds, for the reasons stated above. The term ‘atypical trigeminal neuralgia’ can be unclear in its meaning and thus misleading, so that care is needed when assessing reports of patients included under this diagnosis.

Estimates of the incidence of trigeminal neuralgia vary. It increases with age, being commonest at age 75 years and above, at 11 per 100 000, with a female to male ratio of 1.17:1.0 in one study (Rothman and Monson 1973). Another investigation identified an annual incidence in women of 5.7 per 100 000 and in men of 2.5 per 100 000 (Katusic et al. 1990). In a population study in the United Kingdom, a lifetime prevalence of 0.07 per 1000 was calculated (MacDonald et al. 2000). The condition occurs rarely in young adults, and although the appearance of trigeminal neuralgia in those aged in the third to fifth decades should increase the suspicion of symptomatic trigeminal neuralgia, as defined above, many younger patients fall into the ‘idiopathic’ category. The overall relative risk of trigeminal neuralgia in multiple sclerosis, not age related, has been calculated as 20 (95 per cent confidence interval 4.1–58.6) (Katusic et al. 1990).

The International Headache Society (2004) has suggested that the five key characteristics of trigeminal neuralgia are:

These clinical features are elaborated in further detail in Table 19.3. Trigeminal neuralgia is unilateral in all but 4 per cent of patients, and in the latter, bilateral simultaneous neuralgia is rare (Loeser 1989). The pain is nearly always felt within the second and third divisions of the trigeminal, the two most common sites being the upper lip and nares radiating over the medial cheek towards the eye, and the angle of the mouth radiating along the mandible towards the ear. In some patients, the pain is perceived to originate in the teeth of the upper or lower jaw; these patients are likely to present initially to a dentist. Pain may also be felt along the side of the tongue and in the buccal mucosa and gingiva. Trigeminal neuralgia affecting the ophthalmic division is very uncommon; pain in this area, unless characteristic of trigeminal neuralgia should always raise suspicion of an alternative cause.

Paroxysms of pain in trigeminal neuralgia occur either unprovoked or triggered by a variety of innocuous cutaneous and oral stimuli, including touching and washing the face, shaving, wind blowing on the face, facial movement, chewing, and hot or cold liquids in the mouth (Rasmussen 1991). Paroxysms usually last 15–60 s, but sometimes as long as 2 min. A history of triggering of pain varies between patients, but it is always present.

If asked whether the pain is continuous, some patients will reply that it is, but in trigeminal neuralgia this refers to the fact that there may be very short pain-free intervals between numerous, but distinct paroxysms. Careful elucidation of this feature of the history is needed. The quality of the pain is most often described as shooting, shock-like, like lightning or like electricity, and it is very often severe. During a bout of neuralgia, patients are often reluctant to eat or drink, for fear of provoking the pain, they lose weight and may sometimes become severely dehydrated.

Particularly in the early stages, neuralgia occurs in bouts lasting days to weeks, then may remit for months or even years (Kurland 1958). Over time, there is a tendency for bouts to last longer and for periods of remission to become shorter, so that eventually for some patients, the symptoms become chronic and persistent. Severe pain at night is unusual (Rasmussen 1990 , 1991).

Facial flushing occasionally accompanies trigeminal neuralgia, and appears to be particularly a feature of ophthalmic division neuralgia (Nurmikko et al. 2000).

Another symptom commonly reported by patients with long-standing neuralgia is a milder continuous pain between paroxysms, occurring particularly following a series of rapidly repeated paroxysms with very brief pain-free intervals. This continuous pain may have a burning or dull aching quality, and is felt in the same distribution as the paroxysmal pain. Such pain is not a diagnostic feature of trigeminal neuralgia and indeed the presence of continuous pain at an early stage of the condition should always cause the clinician to question the diagnosis. However, in patients who have undoubtedly suffered from trigeminal neuralgia for several years, a background milder continuous pain is a fairly common feature (Zakrzewska et al. 1999). It does not negate the diagnosis in patients with otherwise typical symptoms and response to treatment.

Depression is a common comorbidity of chronic trigeminal neuralgia (Zakrzewska and Thomas 1993).

Examination. In idiopathic trigeminal neuralgia, there should be no sensory loss on standard clinical testing, though paroxysms of pain may be provoked during facial and oral sensory examination. The obvious severity of the pain and its duration usually leave the examiner in little doubt about the diagnosis. Patients in an active phase of the condition may be reluctant to allow an examination.

Quantitative sensory testing reveals subtle sensory impairment in more than 50 per cent of patients, both in the affected division and in the adjacent division (Nurmikko 1991). Patients should be re-examined periodically; although rare, symptomatic trigeminal neuralgia may be associated with an initially normal sensory examination and sensory loss may not become evident for up to several years (Cheng et al. 1993).

Ideally, all patients presenting with trigeminal neuralgia should be investigated with MRI. This is sensitive in detecting blood vessels in contact with the nerve root, but about one-third of patients will be found to have a similar change on the asymptomatic side (Patel et al. 2003); this change is frequently reported in the scans of patients without trigeminal neuralgia. This emphasizes the fact that the diagnosis of trigeminal neuralgia is made on clinical grounds. MRI is obviously of importance when a diagnosis of multiple sclerosis is being considered. In patients with a short-lived initial bout of neuralgia, it is reasonable to not investigate and to await recurrence, which may not occur for several years.

The place of laser-evoked potentials and other quantitative methods in the assessment of patients with trigeminal neuralgia remains uncertain (Cruccu et al. 2002).

Dandy (1934) identified compression of the trigeminal root entry zone in more than 40 per cent of patients with trigeminal neuralgia coming to operation. The abnormalities causing compression included arterial loops and less commonly, tumours, cysts, aneurysms, or arteriovenous malformations. Later, Gardner and Miklos (1959) drew attention to decompression of the trigeminal root as a treatment for trigeminal neuralgia. However, it was not until Jannetta (1976) reported subtle vascular abnormalities in the root entry zone in 88 out of 100 consecutive patients that the importance of vascular compression in the aetiology of trigeminal neuralgia became widely appreciated. Among the remaining 12 patients in Jannetta’s series, 4 had tumours and 2 had arteriovenous malformations compressing the trigeminal root. Of the 6 patients with multiple sclerosis, 4 had identifiable plaques and 2 had atrophic areas in the trigeminal root entry zone.

Vascular compression is usually caused by the superior cerebellar or anterior inferior cerebellar arteries; the ability of veins to produce compression sufficient to cause trigeminal neuralgia remains controversial. Not all reported series have found such a high incidence of identifiable structural lesions, with estimates of vascular compression ranging from about 65 to 85 per cent (Bederson and Wilson 1989; Loeser 1989).

The importance of vascular compression in the aetiology of trigeminal neuralgia is strongly supported by the success of microvascular decompression, also known as the Jannetta procedure, described below.

Control observations for the intra-operative findings reported in trigeminal neuralgia are hard to obtain. Direct comparison with post-mortem appearances is difficult because the blood vessels collapse, and there is distortion of the contents of the posterior fossa. Histological studies have revealed small areas of demyelination in the trigeminal root and ultrastructural changes in the Gasserian ganglion (Beaver 1967; Kerr 1967). More recent studies have confirmed and expanded these findings. Using electron microscopy, focal demyelination, dysmyelination, and close apposition of demyelinated axons has been observed in biopsies from the region of root compression in patients with trigeminal neuralgia (Love and Coakham 2001). Similar changes are present in patients with multiple sclerosis and trigeminal neuralgia (Love et al. 2001).

Hypotheses of the pathophysiology of trigeminal neuralgia rely heavily on experimental models of nerve injury, though bursting activity in trigeminal axons has been recorded at the time of operation in man (Baumann and Burchiel 1997). Ectopic impulse generation in damaged sensory fibres and dorsal root ganglion cell bodies with damaged peripheral axons is a well-established property (Devor 2005; and see Section 17.4). This may occur as an ongoing phenomenon or triggered by stimulation, either physical or chemical. Such triggered activity may lead to prolonged bursts of impulse activity, termed afterdischarges. These discharges may in turn recruit similar activity in neighbouring damaged afferent fibres, either by tight electrical transmission between adjacent axons, known as ephapses, or by a non-synaptic, non-ephaptic coupling that occurs at sites of nerve injury and in sensory ganglia, so-called crossed afterdischarge (Lisney and Devor 1987). Crossed afterdischarge probably depends on release of neurotransmitter substances or potassium ions into the narrow interstitial spaces between adjacent demyelinated axons (Amir and Devor 1996). Crossed afterdischarge occurs both at sites of nerve damage and in dorsal root ganglion cells with damaged peripheral axons (Devor and Wall 1990). Ephaptic transmission occurs between relatively few axons in areas of nerve injury (Seltzer and Devor 1979). It has often been inferred as a mechanism of neuropathic pain in man, though never directly demonstrated.

Crossed afterdischarge, causing mass recruitment of activity in sufficient numbers of trigeminal axons, is a more likely mechanism to explain the paroxysmal pain of trigeminal neuralgia. This property forms the basis of the ignition hypothesis (Devor et al. 2002).

Both ephaptic crosstalk and crossed afterdischarge lead to excitation of small nociceptive axons by low threshold A beta afferents (Amir and Devor 2000). This would explain the characteristic triggering of painful paroxysms of pain by innocuous peripheral stimuli such as brushing the skin. Interestingly, painful stimuli in trigger areas are less likely to induce painful paroxysms in trigeminal neuralgia (Kugelberg and Lindblom 1959). This clinical finding is matched by the experimental observation that crossed afterdischarge in sensory ganglia is more easily produced by A beta fibre than by C fibre stimulation (Devor and Dubner 1988; Devor and Wall, 1990).

Paroxysms of trigeminal neuralgia are brief, usually lasting 20–30 s, though occasionally as long as 2 min. During a burst of high frequency firing, calcium ions enter the axon, activating calcium- activated potassium channels. Potassiums ions flow out through these channels leading to a hyperpolarized state in which the bursting activity ceases and the axon is refractory for a period (Amir and Devor 1997). This mechanism is likely to explain the short-lived nature of each paroxysm of neuralgia.

In a minority of patients coming to posterior fossa surgery, no vascular or other trigeminal root compression is found. The ignition hypothesis outlined above depends on pathophysiological changes in both the trigeminal root and ganglion. It is possible that in patients in whom no macroscopic root pathology is observed at operation, the major pathology is situated in the ganglion rather than the root. This is supported by observations from the era before treatment with microvascular decompression, when trigeminal ganglionectomy was a standard surgical procedure for the treatment of trigeminal neuralgia; pathological changes in the ganglion were reported in virtually all cases (Beaver 1967; Kerr 1967).

The pathophysiological basis for the remissions that occur in the majority of patients in the earlier course of the condition is more difficult to explain. It is possible that partial remyelination of root axons could raise the thresholds sufficiently to prevent ectopic impulse generation and afterdischarges, but this is speculative. Furthermore, with vascular compression that is presumably fixed, it is difficult to envisage the conditions under which remyelination might occur.

Numerous drugs have been advocated for the treatment of trigeminal neuralgia. With the exception of carbamazepine, for which a systematic review is possible, only single trials of other drugs are available, many of these including relatively few patients. Comparison of the results of these trials is difficult, for the reasons outlined in relation to the drug treatment of neuropathic pain (Section 17.6.3). Medical treatment of trigeminal neuralgia is reviewed by McQuay et al. (1995), Wiffen et al. (2000), and Zakrzewska and Lopez (2004).

By far the most effective drug is carbamazepine (Blom 1963), particularly in the early course of the condition. Overall, the drug relieves trigeminal neuralgia partially or completely in about 70 per cent of patients. Treatment should start with low doses in the region of 300 mg daily, because in many patients the pain responds to low doses and some of the adverse effects are minimized. Drug blood levels are often helpful in determining therapeutic dosage and adverse effect sensitivity. Slow release preparations provide sustained therapeutic blood levels and reduce adverse effects; this is particularly helpful in older patients, who are more prone to develop adverse effects. An allergic rash develops in up to 10 per cent of patients; other serious adverse effects are less common. The latter include blood dyscrasias, a low white cell count being the commonest, abnormal liver function, fluid retention, and hyponatraemia. A systematic review, including reports of 315 patients, calculated a number needed to treat, NNT, of 2.6, with a number needed to harm, NNH, of only 3.7, emphasizing the potential for the drug to produce unacceptable adverse effects, particularly in the elderly (Wiffen et al. 2000).

A common pattern in trigeminal neuralgia is for periods of remission to become shorter and in many patients to disappear. In addition, progressively larger doses of carbamazepine are frequently required to control pain.

Lamotrigine, baclofen, and tizanidine have been assessed in single controlled trials, including only small numbers of patients. Their efficacy remains unproven. Although effective in trigeminal neuralgia, tocainide was withdrawn due to serious adverse effects (Lindstrom and Lindblom 1987). Other drugs advocated for use in trigeminal neuralgia, but never subjected to adequate clinical trials include phenytoin, oxcarbazepine, clonazepam, sodium valproate, gabapentin, and topiramate (Zakrzewska and Lopez 2005). Pimozide is effective, but causes unacceptable adverse effects (Lechin et al. 1989).

Improvements in the surgical treatment of trigeminal neuralgia mean that patients should be considered for one of the procedures described below when carbamazepine begins to lose its effect, when the adverse effects of the drug impair quality of life, and in some patients, as primary treatment. Exhaustive trials of the drugs discussed above, prior to consideration of surgical treatment are no longer appropriate.

Surgical approaches to the treatment of trigeminal neuralgia include several neuroablative procedures and one operation aimed at treating the cause.

Three procedures performed at the level of the Gasserian ganglion, via an approach through a needle introduced into the foramen ovale, have been shown to relieve trigeminal neuralgia:

All these procedures have the advantage of being minimally invasive, but none offers the prospect of permanent pain relief and all are associated with sensory loss, of variable severity, together with a variable degree of weakness of the masseter muscle. Repeat procedures can be performed, but increase the risk of sensory loss, with all the attendant problems including the development of anaesthesia dolorosa. A systematic review found that overall, 40–50 per cent of patients treated by these methods have recurrent neuralgia at 36 months (Lopez et al. 2004). There appears to be little to choose between the procedures, though neuroparalytic keratitis is more common after radiofrequency lesioning, and experience of gamma knife gangliolysis is limited.

Surgical treatment for trigeminal neuralgia is usually considered only when medical treatment fails to control the pain adequately, or is associated with sufficiently unpleasant adverse effects. However, in younger otherwise fit patients, surgery may be considered at an early stage. The choice of procedure depends on the patient’s age, fitness for general anaesthesia, presence of medical comorbidities, and patient choice. Microvascular decompression offers the best prospect of long-term pain relief, with a low incidence of complications, and is usually now recommended for younger patients and those fit to undergo a posterior fossa craniectomy. Of the neuroablative procedures, radiofrequency lesioning is most often performed. It is particularly suitable for the very elderly and those with associated severe medical problems, which can include multiple sclerosis.

Glossopharyngeal neuralgia is a paroxysmal pain occurring in the distribution of the glossopharyngeal nerve, with many similarities to trigeminal neuralgia (Section 20.3.3). It is a rare condition, with an incidence of 0.8 per 100 000, and an average age of onset of 50 years. It is bilateral in about 5 per cent of patients (Rushton et al. 1981; Katusic et al. 1991).

The pain is felt in the posterior part of the tongue, tonsillar fossa, pharynx, or beneath the angle of the jaw, or in the ear. It is paroxysmal, lasting from seconds to 2 min, and is triggered by swallowing, chewing, talking, coughing, and yawning. Attacks are stereotyped in individual patients. Some report a sensation of a foreign body in the throat. Examination reveals no neurological deficit. Glossopharyngeal neuralgia is episodic, in the same way as trigeminal neuralgia, though spontaneous remissions are common (Katusic et al. 1991). It is sometimes associated with sick sinus syndrome, syncope, severe bradycardia, and occasionally asystole (Ferrante et al. 1995).

The distribution of the pain and the associated autonomic features are explained by the complex anatomy of this region. The glossopharyngeal nerve contains motor, somatosensory, visceral sensory, and parasympathetic components, and communicates with the facial and vagus nerves and the sympathetic trunk. The somatosensory innervation provided by the nerve has two parts: the auricular/tympanic branch, supplying the external auditory meatus and tympanic membrane, part of the pinna and the mastoid; and the pharyngeal branch, innervating the pharynx. There is variable communication between pharyngeal and vagal afferents, leading to varying territories of innervation, but together, these nerves supply the soft palate, tonsil, and posterior part of the tongue. The primary sensory afferents from this distribution terminate in the spinal nucleus of the trigeminal, and there are connections between this nucleus and autonomic centres in the medulla. The glossopharyngeal nerve emerges from the anterior part of the jugular foramen, medial to the styloid process, and then curves around the posterior border of the process at the level of the origin of the stylohyoid muscle.

There are similarities to trigeminal neuralgia in relation to the cause of glossopharyngeal neuralgia. High-resolution MRI often reveals vascular compression (Patel et al. 2002; Fiscbach et al. 2003), but other compressive causes such as tumour or an elongated styloid process are sometimes found, and glossopharyngeal neuralgia can also occur in multiple sclerosis (Bruyn 1983).

The characteristic paroxysmal nature of the pain in glossopharyngeal neuralgia, including triggering, in the absence of neurological deficit may lead to a confident diagnosis. However, when the history leaves doubt, a careful otorhinolaryngological assessment is mandatory, to exclude the many other important potential causes of pain in this region. MRI is the best form of imaging, though of unknown sensitivity and specificity (Zakrzewska and Lopez 2005).

Because of the rarity of the condition, there have been no randomized controlled trials of any modality of treatment. However, it is generally accepted that carbamazepine is often effective; in addition, phenytoin, baclofen, gabapentin, and lamotrigine have all been advocated (Nurmikko and Jensen 2005). Surgical treatments reported to be effective include microvascular decompression (Patel et al. 2002) and rhizotomy of glossopharyngeal and sometimes also vagal roots (Kondo 1998), though with perioperative mortality rates of up to 5 per cent and complications including dysphagia and dysphonia.

The ophthalmic division of the trigeminal nerve and the mid- thoracic sensory roots are by far the most common dermatomes affected by acute herpes zoster, known as shingles (Section 21.14.5). The maxillary and mandibular trigeminal divisions may be involved together with the ophthalmic division, but uncommonly in isolation. In other dermatomes on the head and neck, C2 and C3 shingles is unusual. The following sections describe the clinical features, pathology and treatment of postherpetic neuralgia in general. Geniculate herpes zoster, the Ramsay–Hunt syndrome, is described in Section 19.2.4.

The incidence of herpes zoster in immune competent people is about 0.2 per cent in those younger than 50 years and about 1 per cent in those older than 80 years (Kost and Straus 1996). Women are affected more often than men in a ratio of approximately 3 to 2 (Hope-Simpson 1965; Watson et al. 1988a). Postherpetic neuralgia is defined as pain that persists after healing of the acute rash, but it decreases and resolves gradually in many patients over time. At 3 months following the acute eruption, about 10 per cent of patients will experience postherpetic neuralgia (Jackson et al. 1997). Stratification by age in a large study of postherpetic neuralgia revealed that in more than 400 patients, 3 months after the onset, postherpetic neuralgia was present in fewer than 2 per cent of patients younger than 60 years, and in 10 per cent of patients over 60 years. At 1 year following the acute eruption, none of the patients under 60 years had postherpetic neuralgia, and in those older than 60 years, only 3 per cent had postherpetic neuralgia.

At even longer intervals, there is a continuing gradual resolution of postherpetic neuralgia. In a large follow-up study in which more than half of the patients recruited had experienced postherpetic neuralgia for more than 1 year, at a median follow up of 3 years with a range of 3 months to 12 years, 56 per cent of patients had either no pain or pain which had decreased to an intensity of being no longer troublesome (Watson et al. 1988a).

These studies demonstrate the tendency for postherpetic neuralgia to improve in many patients even at long intervals after the acute eruption. This under-appreciated natural history has confounded the design of trials of treatment for postherpetic neuralgia and emphasizes the need for recruitment of large numbers of patients to trials in order to reach valid conclusions about treatment efficacy. In contrast to the general trend towards gradual improvement in postherpetic neuralgia over time, some patients’ pain worsenes with time, despite all efforts to relieve the pain (Watson et al. 1991a).

Pre-eruptive pain is a frequent symptom of acute herpes zoster, usually of 1–2 days’ duration, but on occasions lasting as long as 7 days, and rarely longer than this, leading to delay in diagnosis. The appearance of the characteristic vesicular rash in an appropriate anatomical distribution establishes the diagnosis. The rash is variable in severity and there is a poor correlation between rash severity and either acute neuralgia or postherpetic neuralgia. Making a diagnosis of acute zoster neuralgia in a patient without a rash at any stage should be resisted; it is extremely rare and difficult to prove. Alternative diagnoses should always be considered in such patients.

The pain of acute shingles is often severe and associated with systemic upset, including marked general malaise, anorexia, and sometimes fever. An associated myelitis is an uncommon but well-recognized feature. The painful symptoms of acute shingles and postherpetic neuralgia are qualitatively indistinguishable, the one merging into the other.

Although the primary focus of zoster reactivation is the dorsal root ganglion, and the consequences are predominantly sensory, anterior horn cells are often involved at the same spinal segmental level. This is not clinically obvious when zoster affects mid-thoracic dermatomes, but on the relatively uncommon occasions that upper or lower limb dermatomes are affected, it is not unusual for weakness, wasting and, at relevant levels, reflex loss to occur. The recovery of such motor features tends to take place over weeks or a few months following an episode of acute shingles. When acute shingles affects an abdominal dermatome, motor involvement may be manifest by bulging of the abdominal wall, best seen when the patient is standing.

The ongoing, stimulus-independent pain of postherpetic neuralgia is most often described as burning, raw, gnawing, or tearing. Superimposed stabbing, shock-like paroxysmal pains are common. In addition, evoked stimulus-dependent pains are frequently worse than the ongoing pain. The lightest brushing of clothes against the skin can produce pain of such intensity that patients become immobilized and avoid skin contact in the affected area.

Careful examination reveals that there is hypoaesthesia in scarred, often hypopigmented areas of skin, and severe allodynia in normal appearing skin. The allodynia comprises three types of mechanical hyperalgesia: touch-evoked pain is usually the most evident, but pin prick hyperalgesia and pressure hyperalgesia may also be present (Pappagallo et al. 2000). Mechanical hyperalgesia is common in neuropathic pain from many different causes, but it is particularly severe in postherpetic neuralgia (Scadding and Koltzenburg 2005; Section 17.4).

Comorbidities, particularly depression and sleep disturbance, are major accompaniments of postherpetic neuralgia.

Early investigators documented the pathological changes in the dorsal root ganglion, sensory roots, and peripheral nerves, with demyelination, axonal loss, and lymphocytic infiltration (Head and Campbell 1900; Lhermitte and Nicholas 1924; Denny-Brown et al. 1944; Zachs et al. 1964). Noordenbos (1959) reported a relative loss of large myelinated fibres in intercostal nerves in affected dermatomes in patients with postherpetic neuralgia. This finding supported the idea that an imbalance between activity in small and large fibre sensory input might lead to pain, further elaborated in the gate control theory of Melzack and Wall (1965).

These pathological observations have been extended in two more recent studies. Watson et al. (1988b) reported the autopsy findings in a 67-year-old man who had experienced postherpetic neuralgia in a right T7-8 distribution for 5 years before death. There was right-sided dorsal horn atrophy of the cord from T4 to T8 and fibrosis of the T8 dorsal root ganglion and dorsal root. Unmyelinated fibres appeared normal and this was supported by biochemical marker measures, transmitter levels, and receptor densities. In a subsequent autopsy study, Watson et al. (1991b) examined five patients affected in vivo by acute shingles. Of these, three had experienced postherpetic neuralgia and two had had no pain. Dorsal horn atrophy was present in the three subjects who had had postherpetic neuralgia, while in all five subjects, the peripheral nerve in the affected segment showed severe loss of myelinated axons, particularly larger axons. Staining for substance P and calcium gene-related peptide, CGRP, was absent in the dorsal root ganglia of two subjects with postherpetic neuralgia, but normal in the dorsal horn; however, quantification of unmyelinated fibres was not performed. In one subject who had experienced postherpetic neuralgia for 22 months before death, inflammatory changes and lymphocytic infiltration were found bilaterally in the dorsal root ganglia of four adjacent spinal segments and in their peripheral nerves. This raises the interesting possibility that a chronic inflammatory process can develop following zoster reactivation in some patients, and could provide an explanation for the gradual worsening of pain in a small minority of patients, as reported by Watson et al. (1988a).

In summary, no single pathological change has been identified that is unique to patients with postherpetic neuralgia. The nature and extent of the damage due to zoster reactivation indicate both peripheral and central pathology, and it is thus likely that there are both peripheral and central generators contributing to the neuropathic pain of postherpetic neuralgia (Section 17.4). In a minority of patients with severe sensory loss, indicating marked deafferentation and loss of peripheral sensory nerve fibres, dorsal root ganglion cells, and dorsal root fibres, postherpetic neuralgia is predominantly of central origin. However, in the great majority, severe skin sensitivity is a prominent feature, indicating partial, albeit abnormal peripheral input.

Psychophysical studies in patients with postherpetic neuralgia and severe touch-evoked pain, using measures of afferent C fibre function and density of innervation determined by skin biopsy, have demonstrated chronic abnormal sensitization of unmyelinated nerve fibre terminals in some patients. However, in other patients, pain is associated with marked loss of small fibre functions and partially preserved large fibre functions (Fields et al. 1998). These observations indicate that mechanisms of pain in postherpetic neuralgia are heterogeneous, both peripherally and centrally.

Demonstration of the efficacy of treatments in preventing the development of postherpetic neuralgia following acute shingles must take into account the natural history of the condition. Many studies undertaken prior to the full elucidation of this natural history are flawed for this reason. For example, it was suggested that topical idoxuridine in DMSO applied in the acute stage prevented the development of postherpetic neuralgia (Juel-Jensen et al. 1970). Two trials suggested effectiveness of corticosteroids (Eaglestein et al. 1970; Keczkes and Basheer 1980), though there is a risk of viral dissemination (Merselis et al. 1964). Hopes that acyclovir would prevent the development of postherpetic neuralgia have not been realized, though this treatment may shorten the period of acute zoster neuralgia and promote more rapid healing of the acute rash (Bean et al. 1982; Esman et al. 1982; Balfour et al. 1983), so the drug is indicated in acute shingles. A report that postherpetic neuralgia could be prevented by sympathetic blockade performed during acute shingles (Colding 1969) has not been substantiated.

In a recent study, more than 38 000 immune-competent people over the age of 60 years were immunized with a live attenuated zoster vaccine (Oxman et al. 2005). The results indicate a reduction both of the incidence of acute shingles and subsequent postherpetic neuralgia. Analysis of the data from this large study indicates that approximately 60 individuals need to be treated to prevent one episode of acute shingles, and more than 350 individuals need to be immunized to prevent one person developing postherpetic neuralgia.

Treatment is along the lines set out for the treatment of neuropathic pain in general (Section 17.6). The mechanical hyperalgesia component presents a major therapeutic challenge. Application of cold packs is often helpful, though the partial analgesia produced is shortlived. Topical lignocaine and capsaicin offer partial relief to some, though patients should be warned that initial applications of capsaicin may temporarily exacerbate their pain. Capsaicin is contraindicated near the eye and is thus inappropriate for ophthalmic postherpetic neuralgia. Acupuncture is ineffective (Lewith et al. 1983), and transcutaneous electrical nerve stimulation, TENS, helps some patients but is unpredictable in its effect (Portenoy et al. 1986; Watson et al. 1988a).

Systemic drug therapy should be tried (Section 17.6.3). Surgical treatment has a poor record: dorsal rhizotomy will relieve the peripheral mechanical hyperalgesia, but carries the considerable risk of increasing the component of central neuropathic pain, due to exacerbation of deafferentation, with an overall increase in the intensity of pain.

The effect of intrathecal methyl prednisolone, given once weekly for 4 weeks, to patients with postherpetic neuralgia of at least 1 year’s duration, was reported in a recent controlled trial (Kotani et al. 2000). Pain relief in the treated group of 89 patients was reported as being ‘good’ or ‘excellent’ at follow up 2 years after this treatment. This strikingly good therapeutic effect requires confirmation in other studies.

For ophthalmic postherpetic neuralgia, several surgical procedures have been advocated, including trigeminal rhizotomy, trigeminal tractotomy, cryocoagulation, or alcohol injection of the supraorbital nerve, but none consistently relieves the pain (Loeser 1986; Portenoy et al. 1986). There is also a substantial risk of producing permanent anaesthesia dolorosa with trigeminal rhizotomy and tractotomy, as discussed in relation to the treatment of trigeminal neuralgia. Other treatments which have been helpful in some patients, but not subjected to controlled clinical trials, include thalamic stimulation (Loeser 1986) and nucleus caudalis dorsal root entry lesioning (Bernard et al. 1987) (Section 17.6.8).

Acute herpes zoster affecting the geniculate ganglion causes severe pain deep in the ear, often with retro-auricular radiation. There is continuing debate as to the exact site of the infection, and this may vary between patients. Clinically, the neurological deficit is frequently more extensive than can be explained by involvement solely of the geniculate ganglion, and it has been suggested that the focus of infection may be in the brainstem in some patients.

The sensory root of the geniculate ganglion, the nervus intermedius, supplies the middle and inner ear, the posterior wall of the external auditory canal, part of the pinna, the eustachean tube, and the mastoid air cells. Geniculate zoster is predominantly a condition of late middle and old age. As with zoster elsewhere, pre-eruptive pain may precede the appearance of a rash by several days, often leading to diagnostic difficulty in this situation. The rash affects the external auditory canal and part of the pinna, but is often discreet and is easily missed. Other parts of the facial nerve are affected: facial palsy occurs in almost all patients, with loss of taste on the anterior two-thirds of the tongue due to involvement of the chorda tympani. Involvement of the eighth cranial nerve causes deafness and vertigo. Marked general malaise and a low grade fever are common.

A high index of suspicion is needed to make the diagnosis at an early stage. Acyclovir should be given, but because the syndrome is rare, it is unknown whether or not early treatment leads to a better outcome. Recovery of the facial palsy is often incomplete.

The distribution of sensation supplied by the nervus intermedius is described in Section 19.2.4. Nervus intermedius neuralgia, also known as geniculate neuralgia, is extremely rare. It is characterized by paroxysms of pain lasting for a few seconds or minutes felt deep in the ear, and sometimes also in the posterior pharynx. There is often a trigger area on the posterior wall of the external auditory canal (Furlow 1942). The underlying cause is unknown, and the diagnosis is established by the clinical features, the absence of signs other than a trigger zone in some patients, and exclusion of other causes of otalgia. The condition is sufficiently rare that there are no controlled trials of treatment, which should be along the lines recommended for peripheral neuropathic pain (Section 17.6). In view of the paroxysmal nature and triggering of the pain in some patients, a trial of carbamazepine is reasonable. Various surgical approaches have been reported, with variable success; these include procedures to the nervus intermedius and branches of the glossopharyngeal and vagus nerves (Lovely and Jannetta 1997).

The C2 spinal nerve root runs adjacent to the lateral atlanto-axial joint. It may become involved in inflammatory conditions affecting the joint, by tumours, usually neurofibromas or meningiomas, angiomas, arterial loops, and in subluxation of the atlanto-axial joint, most often seen in rheumatoid disease. Pain due to C2 root compression is felt within the distribution of the root, over the back of the head. It may be intermittent, occurring as hemicranial attacks, or persistent (Jansen et al. 1989a, b), and there is associated sensory impairment.

C2 neuralgia. This describes a condition of unknown cause, which presents with a characteristic clinical picture. There is intermittent, lancinating unilateral occipital pain, often associated with ipsilateral lacrymation and redness of the eye. The pain may occur several times per day and remissions lasting for months are common. Imaging and other investigations are normal. The diagnostic test is a C2 root block using local anaesthetic, which temporarily abolishes the pain. Longer term relief of the pain with root thermocoagulation has been reported (Jansen et al. 1989a, b), but there are no controlled trials.

Occipital neuralgia. This is assumed to be due to damage to or entrapment of the greater or lesser occipital nerves. It can follow whiplash-type neck injuries and may also result from chronic contraction of the posterior nuchal and scalp muscles, though the basis for the condition in many patients is uncertain (Behrman 1983). Pain may be intermittent or persistent, described as a shooting pain starting in the occipital region and radiating towards the vertex, or as a dull, deep, aching pain. It is sometimes provoked by neck movement. There may be local tenderness over the occipital nerves together with nuchal muscle tenderness and mild occipital sensory impairment. Local anaesthetic injections temporarily relieve the pain and in some patients prolonged relief may be obtained with injected corticosteroid.

Neck–tongue syndrome. In the neck–tongue syndrome, sudden turning of the head can produce backwards subluxation of the lateral atlanto-axial joint, stretching the C2 nerve root. This causes episodes of pain in the occipital region lasting seconds or minutes, associated with numbness or paraesthesiae on the ipsilateral side of the tongue, the latter symptoms being due to compression of proprioceptive afferent fibres from the tongue, passing from the ansa hypoglossi to the C2 ventral ramus (Lance and Anthony 1980; Bogduk 1981). The condition usually occurs in normal subjects, but also in patients with rheumatoid disease or congenital joint laxity (Lance and Anthony 1980; Bertoft and Westerberg 1985).

The supraorbital and infraorbital nerves may be damaged by direct trauma to the face, with or without frontal and maxillary fractures. The inferior alveolar nerve is occasionally damaged during wisdom tooth extractions, and the lingual nerve may also be damaged as a result of dental procedures. Pain in all these situations is not paroxysmal, as in trigeminal neuralgia, but is usually continuous, fluctuating in severity, with associated numbness and tingling paraesthesiae within the nerve territory. There is often tenderness and a Tinel sign at the site of damage to the affected nerve. Treatment is as for other peripheral neuropathic pain (Section 17.6).

Painful ophthalmoplegia is the term preferred to include all conditions in which there is some form of ophthalmoplegia associated with pain. In all these conditions pain is felt in the orbital region, but may radiate widely onto the face and the head. The cavernous sinus is densely populated by a number of important structures including the carotid artery, first division of the trigeminal nerve, third, fourth, and sixth cranial nerves, and the sympathetic and parasympathetic supply to the eye. Painful ophthalmoplegia can be produced by a wide range of pathological causes affecting one or more of these structures, including vascular, neoplastic, granulomatous, and infective processes (Table 19.4).

Various terms have been employed to describe these conditions, including superior orbital fissure syndrome, orbital apex syndrome, cavernous sinus syndrome, parasellar syndrome, and Tolosa–Hunt syndrome. While the individual anatomical descriptors remian appropriate, the eponymous title is no longer justifiable. The all-embracing term painful ophthalmoplegia recognizes the frequent anatomical overlap that occurs in individual patients and the lack of pathological specificity previously implied for some of the conditions. It also encourages a logical and systematic approach to diagnosis.

The Tolosa–Hunt syndrome was thought to be exclusively the result of granulomatous infiltration of the cavernous sinus (Hunt et al. 1961; Tolosa 1965) (Section 13.4.3). It is still listed in the International Headache Society taxonomy (Headache Classification, IHS 2004), with clinical diagnostic criteria as follows:

Although previously regarded as a clinically and pathologically distinct condition caused by presumed granulomatous infiltration of the cavernous sinus, the criteria for clinical diagnosis include failure to demonstrate a structural cause, a relapsing course, and a response to corticosteroids. However, although these clinical limits of the syndrome seem to be clearly defined, several variants have been described which cast doubt on the nosological separation of Tolosa–Hunt syndrome as a distinct entity. These include Raeder’s syndrome (Raeder 1924) (Section 18.7.3), the combination of Horner’s syndrome, pain and parasellar cranial nerve involvement, and Gradenigo’s syndrome, a sixth cranial nerve palsy with pain due to lesions at the apex of the petrous temporal bone. In Tolosa–Hunt syndrome itself, optic nerve involvement has been described, indicating anterior extension of the lesion responsible from the cavernous sinus, and the involvement of the maxillary division of the trigeminal nerve in some cases indicates posterior extension of the causative lesion (Smith and Taxdal 1966). Seventh cranial nerve involvement has also been described (Swerdlow 1980), and occasionally the eighth, ninth, tenth, or twelfth cranial nerves (Bogduk 2005).

Furthermore, there are uncertainties about the granulomatous pathological specificity of Tolosa–Hunt syndrome and about the specificity of CT, angiographic, and phlebographic abnormalities said to be characteristic of the condition (Bogduk 2005). Finally, a rapid response to corticosteroid treatment is not unique to Tolosa–Hunt syndrome; it has been reported in patients with painful ophthalmoplegia caused by aneurysms and tumours, including lymphoma, nasopharyngeal carcinoma, pituitary tumours, and metastases, and by fungal infection in the cavernous sinus (Bogduk 2005). For all these reasons it seems appropriate to include all the previously described syndromes under the heading of painful ophthalmoplegia.

Anaesthesia dolorosa refers to pain felt in an area of decreased sensation, due to denervation from either peripheral or central lesions. Thus strictly speaking, central poststroke pain is an example of anaesthesia dolorosa, affecting the face in about 35 per cent of patients (Boivie 2005). However, anaesthesia dolorosa is a term usually used to denote pain due to loss of peripheral sensory input, that is, deafferentation pain. Loss of sensation in the face is particularly likely to lead to anaesthesia dolorosa, compared to other body areas. The pain is described as deep, often diffuse, burning, gnawing, or raw in nature, and when present is often severe. Trigeminal anaesthesia dolorosa now occurs relatively infrequently, as it was seen largely as a result of ablative procedures performed for the treatment of trigeminal neuralgia, including trigeminal rhizotomy and medullary tractotomy, operations now superseded by microvascular decompression. However, as discussed above, it can occur following radiofrequency lesioning (Lopez et al. 2004), and is related to the degree of sensory impairment produced by the lesion.

Pain in the region of the temporomandibular joint is common and is usually transient. In two population surveys conducted by questionnaire, the prevalence of temporomandibular joint pain has been reported as 9.1 and 12 per cent, and associated symptoms of limitation of jaw opening and clicking or popping noises are common (Agerberg and Carlsson 1972; Locker and Grushka 1987).

Terminology. Costen (1934) provided an early description of temporomandibular joint pain and the diagnostic term Costen’s syndrome is still used today. However, three other non-eponymous diagnostic terms are now more commonly employed to describe the syndromes of teamporomandibular joint pain; these are temporomandibular pain and dysfunction syndrome (International Association for the Study of Pain 1994), oromandibular dysfunction (International Headache Society 1988), both of which are associated with dysfunction of the teamporomandibular joint, as their names suggest; and facial arthromyalgia, in which dysfunction is a variable feature (Harris 1974).

Clinical features. In the context of neurological practice, the clinical features of the three temporomandibular joint pain syndromes can be considered together. There is aching in the muscles of mastication, exacerbated by chewing, associated with restriction of jaw movement and clicking or popping sounds. Other associated features include jaw clenching and gnashing of the teeth, jaw locking on opening, and other oral ‘parafunction’, including biting of the tongue, lips, or cheek (International Association for the Study of Pain 1994; International Headache Society 1988). In facial arthromyalgia, temporomandibular joint pain is not necessarily associated with dysfunction or oral parafunction (Harris 1974). Among those seeking medical attention, women outnumber men, and the conditions may present at any age during adult life.

The pain in all these conditions is similar: it is dull and aching and centred on the temporomandibular joint and masticatory muscles, but can radiate widely over the face, to the ear, and occasionally onto the neck. Pain may have been present for weeks to years, it is unilateral or bilateral, it is usually described as continuous and is often, but not always, exacerbated by jaw movement. Mental stress may provoke the pain in some patients. Signs include tenderness of the temporomandibular joint and masticatory muscles, trismus, clicking of the joint on movement, subluxation, and evidence of bruxism.

Pathology. Three main pathophysiological mechanisms have been proposed: psychogenic, meniscal displacement, and malocclusion. It is possible that these are not mutually exclusive.

The psychogenic theory proposes that psychological factors including adverse life events, sleep disturbance, anxiety, and stress, lead to masticatory muscle overactivity and pain (Schwartz 1959; Laskin 1980), and it has been suggested that facial arthromyalgia is more common in those with vulnerable personality types (Feinmann et al. 1984).

The lateral pterygoid muscle alters the position of the meniscus within the temporomandibular joint. It has been proposed that psychological stressors provoke hyperactivity of this muscle, causing the meniscus to be displaced anteromedially in the joint, with loss of attachment to the lateral pole of the condyle, leading to instability in the joint and the development of pain (Juniper 1984). However, anterior displacement of the meniscus, as demonstrated by MRI, is present in 32 per cent of asymptomatic subjects (Kircos et al. 1987), casting doubt on this hypothesis.

Costen (1934) proposed that malocclusion causes pain in the temporomandibular joint. It was later reported that occlusal equilibration relieved pain (Ramijford 1961; Magnusson and Carlsson 1983), though this was based on uncontrolled observations. Subsequent controlled studies have not demonstrated any clear therapeutic effect (Goodman et al. 1976; Dao et al. 1994), and there is no difference in the incidence of malocclusion in patients with facial arthromyalgia and control subjects (Thomson 1971).

Treatment. Many treatments including physical, pharmacological, and psychological measures have been advocated for the treatment of the temporomandibular joint pain disorders (Zakrzewska and Harrison 2003). Of these, there is evidence from randomized controlled trials of a therapeutic effect with antidepressants (Feinmann et al. 1984), diazepam (Jagger 1973), and cognitive behavioural therapy (Harrison et al. 1997).

Hemifacial spasm (Section 20.2.4) is sometimes painful, and patients with longstanding facial palsy sometimes complain of pain on the affected side of the face. This is particularly likely when contracture develops following lower motor neurone palsy, or when hemifacial spasm develops. Oro-facial dyskinesia affecting facial, jaw, and occasionally lingual muscles may also be painful.

Otalgia due to otitis externa and otitis media will usually not present to neurologists, though chronic otitis media can cause widely radiating pain. Malignant otitis media, a condition virtually always occurring in patients with diabetes mellitus, is a chronic condition caused by pseudomonas aeruginosa. It presents with otalgia, followed at intervals of up to 3 months by facial palsy and sometimes other cranial nerve palsies.

Cholesteatomas lead to destructive changes in the middle and inner ear, with secondary infection and bone erosion. They are sometimes painful.

Otalgia as the presenting symptom of geniculate herpes zoster has already been discussed (Section 19.2.4).

Lesions of the temporal bone may present with poorly localized pain in the region of the ear, together with conductive deafness if the middle ear is involved, as for example with glomus jugulare tumours (Section 27.6.3). Occasionally, metastatic deposits in this region of the skull lead to otalgia; this occurs particularly with prostatic cancer, though any of the malignancies commonly metastasizing to bone can cause painful skull deposits. Paget’s disease of bone involving the skull bones may cause localized pain, with a characteristic external appearance and radiological features (Section 27.6.6).

Sinusitis is by far the commonest cause of sinus pain. Bacterial maxillary sinusitis, unilateral or bilateral, usually follows viral upper respiratory infections, associated with nasal obstruction and discharge. Pain is localized over the maxillary antrum and is sometimes also felt in the upper jaw teeth, with tenderness on chewing. Maxillary sinusitis is occasionally caused by a periapical dental abscess. Frontal sinusitis causes pain and tenderness in the supraorbital region. Sphenoid and ethmoid sinusitis produce pain between or behind the eyes. Pain is characteristically exacerbated by bending, and relieved by spontaneous or surgical drainage of the infected sinus. Plain skull radiographs, or with greater sensitivity, CT scans show opacification of the affected sinuses and sometimes a fluid level.

Fungal infection of the sinuses is most frequently, but not exclusively, seen in immunocompromized patients. In the rhinocerebral syndrome there is fungal infection progressively involving the sinuses, orbits, and brain, occurring most often in patients with diabetes mellitus (DeShazo et al. 1997) (Section 43.2.7).

Tumours within the sinuses lead to sinus pain, and nasal polyps and severe allergic rhinitis can lead to obstruction of the sinuses causing pain in the absence of infection. A markedly deviated nasal septum can obstruct sinus drainage and also cause pain due to pressure on one of the bony turbinates.

Toothache is the province of the dental surgeon. However, although dental pain is usually well localized, it can be diffuse and lead to diagnostic difficulty. Neurologists should be aware of the leading causes of odontalgia (International Association for the Study of Pain 1994; Zakrzewska and Harrison 2003).

Dentinoenamel defects, due to caries or trauma, cause shortlasting and sometimes diffuse orofacial pain. Local dental stimuli evoke the pain, which does not usually occur in the absence of stimulation.

Pulpitis is infection of the tooth pulp due to deep caries. Pain may again be diffuse and occurs without local stimulation. A history of exacerbation by chewing and hot and cold liquids may lead to an erroneous diagnosis of trigeminal neuralgia and the pain in the upper jaw may also mimic maxillary sinusitis. Without treatment, pulpitis can progress to periapical periodontitis and abscess.

Periapical periodontitis and abscess cause severe pain in the affected tooth and adjacent gingiva, and sometimes widely radiating pain. Cursory examination of the teeth may not reveal obvious disease, but the gingiva are often inflamed and a gum boil may discharge into the mouth.

Gingival pain due to local trauma or infection can usually be easily identified but when associated with pericoronitis, a bacterial infection affecting supporting tissues surrounding an impacted or erupting tooth, may lead to diffuse pain.

Cracked tooth syndrome, due to a crack in a tooth, causes local pain provoked by chewing; part of the tooth cusp may fracture.

Dry socket refers to a painful condition following tooth extraction, usually from the lower jaw. It is due to localized osteitis and there is often associated submandibular lymphadenitis. After tooth extraction, clotted blood normally fills the socket, but this is inhibited if excessive adrenaline is used with the local anaesthetic. If the clot is washed out or broken down by infection, this may also result in a dry socket. Food impaction in the socket causes severe pain and halitosis. Treatment consists of washing out and packing the socket.

Atypical odontalgia occurs predominantly in women and is defined as severe throbbing pain in a tooth or teeth in the absence of major pathology. In the condition, teeth become both spontaneously painful and hypersensitive to stimuli, particularly heat and cold. Pain may radiate widely, as far as the temporomandibular joints, and associated oral dysaesthetic symptoms are common. The condition is considered to be of psychological origin, akin to atypical facial pain (Section 19.6), with which there is overlap clinically, associated either with depression or representing a monosymptomatic hypochondriacal disorder (Rees and Harris 1979).

Burning mouth syndrome, also known as glossodynia, burning tongue, or oral dysaesthesia, is characterized by burning pain, present predominantly on the tip and lateral borders of the tongue, but also sometimes on the palate, alveolar mucosa, and lips. It nearly always affects post-menopausal women over the age of 50 years. Associated symptoms include xerostomia, dysgeusia, and thirst. Anxiety and depression are common comorbidities. Symptoms are exacerbated by emotion, fatigue, and hot drinks. Temporary relief is obtained by sleeping, eating, consuming cold drinks, and alcohol.

It is important to exclude treatable conditions that can cause diffuse pain in the mouth, including bacterial and fungal infection, allergies, oesophageal reflux, xerostomia as part of Sjogren’s syndrome, iron, vitamin B12, and folate deficiencies, and diabetes mellitus.

Until recently, the pathogenesis of the condition has been obscure and trials of treatment on the basis of presumed vitamin deficiency or infection have been disappointing; these treatments include iron, vitamins, zinc, and antifungal drugs. However, tongue biopsies in patients with burning mouth syndrome have shown lower densities of unmyelinated epithelial nerve fibres compared with controls, with evidence of axonal degeneration (Lauria et al. 2005). This evidence suggests that burning mouth syndrome may be a trigeminal small fibre neuropathy.

Tricyclic antidepressant drugs are often given, but a recent Cochrane review did not find convincing evidence of a therapeutic effect for these or any other class of drug in burning mouth syndrome (Zakrzewska et al. 2005).

Submandibular gland disease includes duct obstruction, inflammation, infection, and rarely tumour. These all lead to local pain, swelling, and tenderness of the gland, causing few diagnostic problems. Lesions of the parotid can be more difficult: pain is often diffuse, affecting most of the side of the face. In addition, mild to moderate gland swelling may not be clinically obvious. The development of a facial palsy suggests a mixed parotid tumour. Painful symmetrical swelling of the salivary glands occurs in mumps infection, and enlargement of one or both parotids is a feature of sarcoidosis. When facial pain is considered to be due to a parotid lesion, imaging with CT or MR is helpful and a surgical opinion should be obtained.

Pain is often the first symptom of both internal carotid and vertebral artery dissection and may precede the onset of symptoms and signs of cerebral ischaemia by hours or days (Section 35.4.4). In carotid dissection, pain is usually ipsilateral to the dissection and is felt in the face, head or neck. In a minority, pain is bilateral. In vertebral artery dissection, unilateral or bilateral neck pain and headache occur, sometimes with facial pain, though the last may be a specific localizing symptom of brainstem ischaemia produced by the dissection. Typically, focal symptoms and signs develop at an interval following the onset of neck pain and headache.

Eagle (1937, 1958) described a constellation of symptoms resulting from elongation of the styloid process or calcification or ossification of the stylohyoid ligament, now known as Eagle’s syndrome. Although rare, neurologists should be aware of this condition, particularly as recognition leads to surgical treatment that is often successful. The styloid process originates from the temporal bone medial and anterior to the stylomastoid foramen. The process points anteromedially and is bordered on medial and lateral sides by the internal and external carotid arteries respectively. Three muscles are attached to the process: stylopharyngeus inervated by the glossopharyngeal nerve, stylohyoid, the facial nerve, and styloglossus, the hypoglossal nerve. The stylohyoid and stylomandibular ligaments also originate from the process. The internal jugular vein and the glossopharyngeal, vagus, and hypoglossal nerves lie medial to the process.

Patients with Eagle’s syndrome are typically aged 30–50 years, with a slight female preponderance. Symptoms may be intermittent or continuous and include pain in the throat, sensation of a foreign body in the pharynx, dysphagia, otalgia, mandibular and facial pain, vertigo, and syncope. Head turning towards the side of the pain, with the neck flexed, may provoke the pain, and is a symptom well worth enquiring about in patients with pharyngeal pain of obscure origin. Less commonly, symptoms arise due to mechanical irritation of the external and internal carotid arteries, carotidynia, with a wide distribution of pain. With external carotid artery irritation, the pain radiation includes the eye, ear, mandible, face, soft palate, and nose; when the internal carotid artery is involved, pain may radiate to the whole head (Correll et al. 1979).

The symptoms can often be provoked by palpation of the styloid process, which may be obviously elongated. Head turning towards the side of the pain, with neck flexion may elicit the pain. Plain X-rays or CT scans demonstrate an elongated styloid process, allow measurement of length, and may also show mineralization of the stylohyoid complex.

The cause of elongation of the styloid process and abnormal bone mineralization in Eagle’s syndrome is unknown in the majority of patients. It is considered by some otorhinolaryngologists that trauma from tonsillectomy may induce bone formation, leading to an elongated styloid process or ossified stylohyoid ligament. Recurrent trauma to the stylohyoid ligament due to neck movement is thought to be an aetiological factor in some patients (Salamone et al. 2004).

The wide distribution of symptoms and their non-specific nature can make diagnosis of this uncommon condition difficult. The differential diagnosis is extensive and can include chronic pharyngotonsillitis, otitis media, mastoiditis, dental pain, pharyngeal foreign body, submandibular salivary gland disease, and tumours of the pharynx or base of the tongue. It is common for patients to be seen by several doctors, including psychiatrists, before the diagnosis is established (Beder et al. 2005).

Treatment is excision of the elongated part of the styloid process, and this is curative in the majority of patients (Beder et al. 2005; Mendelsohn et al. 2006).

The term atypical facial pain is used in the United Kingdom to refer to pain of psychological origin (Section 4.7.9). However this usage is not universally adopted, and the term is sometimes used in the clinical literature to denote atypical forms of organically determined conditions. The International Headache Society defines atypical facial pain as persistent facial pain that does not have the characteristics of the cranial neuralgias and is not associated with physical signs or a demonstrable organic cause. Pain may be initiated by an operative procedure or injury to the face, teeth, or oral tissues (International Headache Society 1988). While this definition indicates an absence of organic disease, it does not go as far as stating positively that the condition has a psychologically determined basis.

There is a history of previous dental treatment or injury prior to the onset of symptoms in about 50 per cent of patients (Mock et al. 1985). Some studies have drawn attention to the frequency of depression and anxiety in atypical facial pain (Lesse 1956; Moore and Nally 1975).

Atypical facial pain is commonest in women, usually presenting in middle age. However, robust epidemiological data are lacking. Patients present with poorly localized pain affecting non-muscular parts of the face. There is a tendency for the pain to spread over time, and symptoms may persist for years. Pain usually starts on one side of the face, but often becomes bilateral and frequently extends beyond trigeminal territory on the head and upper neck. It may be provoked by fatigue and psychological stressors, and physical provoking factors are described by some patients, though without the characteristic features of triggering as found in trigeminal neuralgia. The pain is often described as deep, aching, and throbbing. It is frequently severe and may markedly restrict normal activities. Symptoms of anxiety and depression are commonly present, though patients often deny feeling depressed. There may be a history of repeated dental treatments, undertaken in attempts to relieve the symptoms. The overlap with atypical odontalgia has already been mentioned.

Examination reveals no physical signs except deep tenderness of the face in some patients. Patients may appear agitated and distressed and there may be obvious depressive features. All investigations are normal.

Treatment with antidepressant medication is often effective (Lascelles 1966; Harrison et al. 1997), and psychiatric assessment is advisable for the majority of patients. Diagnostic review is essential for those patients not responding to medication.

Ophthalmic disease causes pain that is usually centred on the eye, but which can radiate widely onto the face and head. Cervical spine degenerative disease frequently leads to pain both in the spine and in the head, particularly posteriorly, often associated with nuchal muscle tenderness. Myocardial ischaemia may present with pain in the lower jaw, anterior neck, and throat, in the absence of the usual distribution of central chest pain, with radiation to the left arm. In thoracic outlet syndrome (Section 22.5.3) pain in the root of the neck, radiating down the arm is the characteristic distribution, referred pain may be experienced on the ipsilateral side of the face and head by a minority of patients.