Central neuropathic facial pain

INTRODUCTION — Central facial pain is a syndrome characterized by intermittent or continuous neuropathic pain caused by a lesion or dysfunction in the central nervous system. Pain may be accompanied by sensory loss and can develop weeks to months or even years after the onset of the central lesion.

The International Classification of Headache Disorders (ICHD) recognizes two entities that are central causes of facial pain [1]:

●Central neuropathic pain attributed to multiple sclerosis

●Central poststroke pain

This topic will discuss the clinical features, diagnosis, and management of central neuropathic facial pain. Other causes of neuropathic facial pain, including persistent idiopathic (atypical) facial pain, cranial neuralgias, and painful cranial neuropathies, are discussed separately. (See "Overview of craniofacial pain".)

Other manifestations of pain associated with multiple sclerosis and stroke are discussed elsewhere. (See "Symptom management of multiple sclerosis in adults", section on 'Pain' and "Neuropalliative care of stroke", section on 'Pain'.)

PATHOPHYSIOLOGY

Anatomy — Central neuropathic pain is due to dysfunction in the central nervous system. Neuropathic facial pain may be caused by a lesion at any level of the central nervous system involved in facial sensation, from the spinal trigeminal nucleus or spinal dorsal horn rostral up to the cerebral cortex. Common sites include the lateral aspect of the medulla, pontine base, and lateral or posterior thalamus [2,3]. The risk for developing central pain may be higher when the spinothalamic and quintothalamic pathways are affected compared to suprathalamic lesions involving other pathways [4].

Pathogenesis — The underlying pathogenesis of central neuropathic facial pain is uncertain. The pathophysiology may be similar to neuropathic pain elsewhere in the body or due to other types of lesions, due to overlapping features and associated conditions [5]. Several peripheral and central mechanisms have been implicated in neuropathic pain pathophysiology (brain, spinal cord, and descending modulating systems) [6]. However, the certainty in the underlying mechanisms of central neuropathic facial pain is limited by observed variability in clinical features and localization within the central nervous system.

Although the mechanisms of central neuropathic facial pain remain poorly understood [7], two general mechanisms have been implicated:

●Irritative lesion hypothesis – An "irritative lesion" has been posited to lead to excess activity in otherwise normal somatosensory pathways. Lesion-induced hyperactivity may impair physiologic balance of facilitation and inhibition [8,9].

●Postdenervation sensitization hypothesis – Neurons remote from the lesion site may become hyperactive and hypersensitive after losing regulatory synaptic inputs through denervation [4]. This release from inhibition may result in an abnormal, sensitized state of central structures leading to persistent pain in the absence of ongoing tissue injury [10].

CAUSE-SPECIFIC EPIDEMIOLOGY — The overall prevalence of central neuropathic facial pain is uncertain, as rates vary by underlying cause and because available epidemiologic data are limited.

●Central neuropathic pain from multiple sclerosis – In a meta-analysis of 24 observational studies of neuropathic pain among patients with multiple sclerosis, the overall prevalence of neuropathic pain was approximately 27 percent [11]. However, the proportion of patients with neuropathic facial pain in these patients was not specified. General facial pain has been reported to occur in up to 5 percent of patients with multiple sclerosis, but many of these cases appear to be due to trigeminal (peripheral) neuralgia [12]. In one study of 377 patients with early multiple sclerosis (mean disease duration 4.2 years), the prevalence of neuropathic pain was 4.2 percent [13]. Of these 16 patients, only one patient had isolated facial pain (trigeminal neuralgia), five had facial pain combined with pain in extremities, and the rest had other locations of neuropathic pain.

●Poststroke pain – Central facial pain affects from 0.5 up to 8 percent of patients following stroke [14-17]. Among patients with stroke producing sensory deficits, the prevalence of central poststroke pain may be as high as 18 percent [16].

CLINICAL FEATURES

Facial pain — Clinically, the presentation of central neuropathic facial pain can vary significantly in severity, character, and location.

●Severity – Pain intensity can range from mild to excruciating [4]. The pain can be a great burden in some patients due to severity and refractoriness, leading to severe depression or even suicide [18].

●Character of pain – The character of central neuropathic facial pain is variable [19,20]. Patients may report muscle pain, felt as cramping, constriction, or crushing. Others may feel a burning- or freezing-type dysesthesia or circulatory-like pain (pins and needles, stings, jabs).

Nevertheless, central pain can often be difficult for patients to describe, and many patients report more than one type of pain [4]. Bizarre, vague terms such as troublesome, annoying, or tiring might be utilized by patients attempting to explain what they are feeling [19,21].

Internal and external stimuli can exacerbate or trigger central pain. Common triggers include cold, movement, light touch, or emotional distress [4]. These triggers may produce allodynia (interpretation of nonpainful stimuli as painful) and/or hyperalgesia (a heightened response to noxious stimuli).

●Temporal features – Neuropathic facial pain can be constant or intermittent and may occur spontaneously or in response to a stimulus. Most patients report constant (non-neuralgic) pain that is associated with spontaneous or triggered exacerbations. Other patients have intermittent (neuralgic) pain that is paroxysmal, episodic, and shooting/lancinating in quality (similar to the pain with trigeminal neuralgia) [7,22]. Neuropathic facial pain that is exclusively neuralgic is uncommon but has been reported in some patients with pontine ischemic infarction [23,24].

Central neuropathic facial pain is typically a persistent, chronic condition. (See 'Prognosis' below.)

●Location – Central neuropathic facial pain can occur in a discrete area or the entire side of the face/head. Pain can also more broadly involve the entire craniocervical region [4].

Additional sites of neuropathic pain symptoms may be present elsewhere in the body depending on the localization of the underlying central lesion [25,26].

Attributable central lesion

Sensory symptoms — Central neuropathic facial pain results from ischemic or demyelinating central nervous system lesions that produce initial or persistent sensory loss. Patients frequently have hypoesthesia, anesthesia, and/or hypoalgesia associated with the pain. Abnormalities in temperature sensation may be reported by patients [27]. However, central pain can also occur after minor or clinically silent brain lesions, including those that leave no permanent, clinically detectable sensory loss [7]. In some patients, the causal central lesion may be identified by imaging performed following the onset of facial pain symptoms.

Relation to onset of pain — Onset of central neuropathic facial pain typically occurs weeks to months following the onset of transiently lost or impaired sensation from a lesion affecting somatosensory pathways [27]. However, in some patients, the onset of facial pain may coincide with the acute central lesion. In others, the onset of the pain may be delayed for years after the insult [4,16,27]. In a systematic review of 16 studies that reported the incidence of central poststroke pain, symptoms occurred with stroke onset in 26 percent of patients, within one month in 31 percent, between one month and one year in 41 percent, and more than 12 months after the stroke in 5 percent of patients [28].

DIAGNOSIS — The diagnosis of central neuropathic facial pain should be considered in patients with unilateral or bilateral facial pain that occurs following onset of a demyelinating or ischemic lesion of the central nervous system. The diagnosis is made in patients who fulfill diagnostic criteria for either central neuropathic pain attributed to multiple sclerosis or central poststroke pain. Diagnostic testing, including neuroimaging, is required to identify a causal lesion and exclude alternative causes of pain.

The diagnosis of central neuropathic pain conditions from demyelinating or ischemic lesions that do not involve the head/face is discussed separately. (See "Symptom management of multiple sclerosis in adults", section on 'Pain' and "Neuropalliative care of stroke", section on 'Pain'.)

Diagnostic criteria

Central neuropathic pain attributed to multiple sclerosis — Central neuropathic pain attributed to multiple sclerosis is described as unilateral or bilateral craniocervical pain of varying presentation, with or without sensory changes, attributed to a demyelinating lesion of the central connections of the trigeminal nerve in an individual with multiple sclerosis [1].

Diagnostic criteria, according to the International Classification of Headache Disorders, 3^rd edition (ICHD-3), require all of the following [1]:

●Facial and/or head pain

●Multiple sclerosis has been diagnosed with magnetic resonance imaging (MRI) demonstration of a demyelinating lesion in the brain stem or ascending projections of the trigeminal nuclei

●Pain has developed in temporal relation to the demyelinating lesion or led to its discovery

●Not better accounted for by another ICHD-3 diagnosis

The pain may be continuous or paroxysmal. Other associated sensory disturbances may include dysesthesia, hypoesthesia, anesthesia, hypoalgesia, and paresthesia [1].

Patients with multiple sclerosis who have unilateral pain with the characteristics of (secondary) trigeminal neuralgia due to a multiple sclerosis plaque affecting the peripheral trigeminal nerve root should be classified instead as having trigeminal neuralgia attributed to multiple sclerosis [1]. (See "Trigeminal neuralgia", section on 'Mechanisms'.)

Central poststroke pain — Central poststroke pain is described as usually unilateral facial and/or head pain, with variable presentation, involving part or the whole of the craniocervical region and associated with impaired sensation that is caused by stroke [1]. It is not caused by a lesion of the peripheral trigeminal nerve or other cranial or cervical nerves. Depending on the specific site of the lesion, the ipsilateral trunk and/or limbs may also be affected.

Diagnostic criteria for central poststroke pain according to the ICHD-3 require all of the following [1]:

●Facial and/or head pain

●Ischemic or hemorrhagic stroke has occurred

●Evidence of causation demonstrated by both of the following:

•Pain has developed within six months after the stroke

•Imaging (usually MRI) has demonstrated a vascular lesion in an appropriate site

●Not better accounted for by another ICHD-3 diagnosis

The pain is usually persistent but can also be paroxysmal [18].

In several studies and the author's experience, the onset of central poststroke pain may be delayed months or even years after the stroke, in contradistinction to the ICHD-3 diagnostic criteria [4]. (See 'Relation to onset of pain' above.)

Evaluation — The evaluation may be straightforward for patients with facial pain in the distribution of a known, recently preceding history of a demyelinating or ischemic event that produced sensory deficit. However, attributing facial pain symptoms with a central lesion may be more difficult when symptoms are atypical or a history of preceding central event is either absent or remote (eg, >6 months).

●Examination – For patients who present with clinical features suggestive of central neuropathic facial pain, evaluation begins with a general and neurologic examination. Direct inspection of the face, ear, mouth, and neck may identify swelling or a rash that would suggest an alternative condition. (See 'Differential diagnosis' below.)

Patients with central facial pain may also report allodynia or hyperalgesia on sensory testing. (See 'Facial pain' above.)

●Neuroimaging – Neuroimaging is required to identify an underlying demyelinating or ischemic causal lesion for central pain symptoms, to evaluate for acute lesions that may require cause-specific treatment, and to exclude alternative conditions. Brain MRI with gadolinium contrast is the preferred imaging modality. In addition, vascular imaging with magnetic resonance (or computed tomography [CT]) angiography of the head is also performed for patients with neuralgic pain to evaluate for neurovascular compression associated with trigeminal neuralgia.

Head CT with contrast may be performed as an alternative for patients unable to undergo a brain MRI. However, head CT is less sensitive than MRI for many central lesions that produce central neuropathic facial pain due to their small size, demyelinative etiology, and/or brain stem location.

MRI findings in central neuropathic facial pain include acute and chronic ischemic or demyelinative lesions that involve trigeminal nuclei or ascending projections, spinothalamic pathways, and/or associated cortical regions. Lesions producing central facial pain may be found in the medulla, pons, thalamus, or cerebral hemispheres [24-26,29]. Specific imaging findings in multiple sclerosis and stroke are discussed elsewhere. (See "Evaluation and diagnosis of multiple sclerosis in adults", section on 'Magnetic resonance imaging' and "Neuroimaging of acute stroke".)

●Other testing – Neurophysiologic testing has limited diagnostic utility but may be performed for selected patients with nondiagnostic imaging or atypical features or features of uncertain relation to a central lesion on imaging. Somatosensory evoked potential testing may show abnormalities in patients with poststroke pain [3,30]. Trigeminal reflex testing may be used to localize facial symptoms to the peripheral trigeminal nerve.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of central neuropathic facial pain includes other conditions that produce facial pain. These include cranial neuralgias such as trigeminal neuralgia and secondary causes of facial pain such as dental pain or giant cell arteritis. These conditions may be distinguished by specific clinical features and/or neuroimaging findings.

Specific alternative conditions vary by the site and character of pain. (See "Overview of craniofacial pain".)

TREATMENT — Pharmacotherapy is the mainstay of the treatment of central neuropathic facial pain. Interventional and surgical treatments may be used for refractory cases. Therapy for central pain can be challenging. Symptoms may be severe, persistent, and often refractory to multiple treatment modalities.

Referral for specialty care should be pursued if the diagnosis is uncertain or if the patient fails to respond to usual management.

Limited scientific evidence is available regarding pharmacotherapy for central neuropathic facial pain [22]. Treatment is mostly based on evidence for other types of neuropathic pain, expert opinion, and consensus statements [4]. Various guideline groups have recommended similar although somewhat different treatment strategies for neuropathic pain [31-34]. However, it is unknown whether a treatment that is effective in one central pain syndrome will be effective in another [31]. It is therefore difficult to apply available guidelines for neuropathic or central pain management to facial pain specifically [32].

Initial treatment options for most patients — For most patients with central neuropathic facial pain, we suggest tricyclic antidepressants as initial pharmacologic therapy based on limited data for central facial pain as well as efficacy in other forms of neuropathic pain. Amitriptyline is the most studied tricyclic for central pain. We use gabapentinoids for patients with an intolerance, contraindication, or suboptimal response to tricyclic antidepressants.

Some patients who have neuropathic facial pain that is both neuralgic (episodic, lancinating) and non-neuralgic (constant) may benefit from combining carbamazepine (for neuralgic pain) with amitriptyline or gabapentin/pregabalin (for steady, non-neuralgic pain). (See 'Carbamazepine for patients with neuralgic pain' below.)

Referral for specialty care, including evaluation for interventional options, should be pursued if the diagnosis is uncertain or if the patient fails to respond to usual management.

Tricyclic antidepressants — For most patients with central neuropathic facial pain, we use amitriptyline as initial pharmacologic therapy. Alternative agents in this class may be used for patients with intolerance to amitriptyline, including nortriptyline or protriptyline.

Amitriptyline is started at 10 to 25 mg nightly and titrated as needed and tolerated by 10 to 25 mg steps every one to three weeks up to a maximum dose of 150 mg nightly is reached.

Amitriptyline and most other tricyclics are sedating. Additional side effects of tricyclics include dry mouth, constipation, tachycardia, palpitations, orthostatic hypotension, weight gain, blurred vision, and urinary retention. Confusion can occur, particularly in older adults. These agents should be avoided or used with caution in patients with cardiovascular disease (including stroke).

Amitriptyline has been shown to be effective in several small randomized controlled trials of patients with central poststroke pain [18,35,36]. However, other meta-analyses and systematic reviews have not found a benefit for amitriptyline [37].

Gabapentinoids — We use gabapentinoids as initial treatment of central neuropathic facial pain for patients with an intolerance or contraindication to tricyclic antidepressants, such as those with cardiovascular disease (including stroke). Gabapentinoids are also used for patients with a suboptimal response to tricyclic antidepressants. Options in this class include gabapentin or pregabalin.

●Gabapentin – Gabapentin is started at 100 to 300 mg daily and titrated as needed and tolerated for pain relief. In patients who are poorly tolerant of side effects, the titration can be as low as 100 mg daily. Adequate relief is typically achieved with gabapentin doses ranging from 900 to 2400 mg daily, given in three divided doses [38]. Doses as high as 3600 mg daily are tolerated by most patients.

The most common adverse effects of gabapentin include somnolence, diarrhea, mood swings, ataxia, fatigue, nausea, and dizziness.

●Pregabalin – Pregabalin is typically started at 25 to 50 mg once daily then increased as needed and tolerated by 50 to 150 mg/day (given in two to three divided doses) at weekly intervals up to a maximum total daily dose of 600 mg daily.

Common side effects of pregabalin include dizziness, somnolence, dry mouth, peripheral edema, and weight gain. Pregabalin can also cause sedation and confusion. It is designated as a schedule V controlled substance in the United States because it has been reported to cause euphoria. When stopping the drug, it should be tapered over a week since withdrawal symptoms may occur.

A network meta-analysis of 13 studies that assessed medications for poststroke pain suggested that pregabalin and gabapentin were the most effective (compared with amitriptyline, carbamazepine, and others) but also caused the most frequent adverse events [36]. Certainty of these conclusions were limited by small number and size of studies, low quality of data with risk of bias, and short-term outcome assessments. Other studies have also suggested that gabapentin and pregabalin are effective for central poststroke pain [18,39].

Carbamazepine for patients with neuralgic pain — For patients with neuralgic (brief, recurring, lancinating attacks of) facial pain attributed to multiple sclerosis or stroke, we suggest carbamazepine as initial therapy. Evidence is from expert opinion and largely based on efficacy for neuralgic pain due to secondary trigeminal neuralgia [4,40].

Carbamazepine is started at 100 to 200 mg daily; the dose can be increased over several weeks by 200 mg increments as needed for pain relief up to a maximum total dose of 1200 mg/day.

Carbamazepine is associated with rare but serious side effects, including agranulocytosis and aplastic anemia. The Stevens-Johnson syndrome and toxic epidermal necrolysis are additional rare complications, particularly during the first eight weeks of therapy, and are significantly more common (estimated incidence of 5 percent) among patients with the HLA-B*1502 (human leukocyte antigen) allele [41]. This allele occurs almost exclusively in patients of South Asian ancestry. Screening for this allele is recommended in patients of these ethnic groups prior to starting carbamazepine. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'HLA polymorphism and pharmacogenetics'.)

Limited evidence in patients with poststroke pain suggests a possible but uncertain benefit for carbamazepine [36,37].

Alternative treatments — We add or switch to an alternative agent for patients with an inadequate response or contraindication to initial therapy. Several other agents have been used for central neuropathic facial pain and other forms of central pain. Limited evidence from small trials and cohort studies suggests a benefit for lamotrigine, duloxetine, and venlafaxine [18,36,39,42-44].

●Lamotrigine – Lamotrigine is typically started at 25 mg daily for the first two weeks of therapy. The dose can then be increased as needed and tolerated to 50 mg daily for weeks 3 and 4, then by 50 mg increments every one to two weeks up to a daily maximum of 400 mg.

Rash is the most common adverse effect associated with lamotrigine treatment and requires discontinuation of the drug since a hypersensitivity reaction may result and lead to life-threatening complications such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Other common adverse effects include nausea and dizziness. Lamotrigine should be tapered slowly over weeks to reduce the risk of withdrawal symptoms.

●Duloxetine – Duloxetine is started at 30 mg daily and can be increased to 60 mg daily as needed and if tolerated. Common adverse reactions with duloxetine include nausea, drowsiness, and weight loss.

●Venlafaxine – Venlafaxine is typically started at 37.5 mg daily. The dose may be increased as needed and tolerated to 75 mg after one week then by an additional 75 mg each subsequent week up to a maximum dosage of 225 mg. Nausea and dizziness are common adverse effects with venlafaxine.

Other drugs that have been used in case series and reports of patients with neuropathic facial pain include [22,45-47]:

●Phenytoin

●Clonazepam

●Valproate

●Prochlorperazine

●Mexiletine

●Baclofen

Avoid opioids — We do not use opioids to treat central neuropathic facial pain. Importantly, a position statement from the American Academy of Neurology (AAN) regarding opioid use for chronic noncancer pain stated that "there is no substantial evidence for maintenance of pain relief or improved function over long periods of time without incurring serious risk of overdose, dependence, or addiction" [48]. While there is evidence for short-term pain relief using opioids (if used), these should only be part of the pain management strategy. The risks of chronic opioid therapy for chronic conditions such as headache, fibromyalgia, and chronic low back pain likely outweigh the benefits [48]. It is unclear if the same applies to chronic central neuropathic face pain, but the possibility exists, warranting judicious opioid use if at all.

Interventional treatment options for refractory cases — Neuromodulation and invasive procedures to treat central neuropathic facial pain are reserved for patients with significant disability who have failed noninvasive measures [22,49]. Options include:

●Transcutaneous electrical nerve stimulation [4,50]

●Motor cortex stimulation [51,52]

●Spinal cord stimulation [53-55]

●Repetitive transcranial magnetic stimulation [56,57]

The evidence of efficacy for central neuropathic facial pain is limited to case reports and series as well as data for other forms of central pain. In a systematic review of case series that included 210 patients with poststroke pain who underwent motor cortex stimulation procedures, the rate of favorable response (≥40 percent pain relief) was reported in 45 percent at one year. The durable effect is uncertain; relief after motor cortex stimulation has been reported to subside with time [22,58].

Deep brain stimulation and destructive lesions, such as radiofrequency ablation or thalamotomy, are last-resort procedures only considered after other alternatives have failed and only in specialized centers [4]. Though they may provide pain relief in a subset of patients, pain may recur after these procedures as well [59-61].

Neuromodulatory and interventional options for neuropathic pain are discussed in greater detail separately. (See "Approach to the management of chronic non-cancer pain in adults", section on 'Physical modalities' and "Approach to the management of chronic non-cancer pain in adults", section on 'Interventional therapy for chronic pain'.)

PROGNOSIS — Central neuropathic facial pain is a chronic, often lifelong condition that is variably responsive to treatment [62,63]. Severity of pain typically remains stable throughout the course of symptoms. Some patients are effectively managed with initial pharmacotherapy, while many others require multiple medication trials to achieve sustained pain relief. For some patients, symptoms may be partially or completely refractory to therapeutic options.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neuropathic pain".)

SUMMARY AND RECOMMENDATIONS

●Definition and causes – Central facial pain is characterized by intermittent or continuous neuropathic pain caused by a lesion or dysfunction in the central nervous system. Subtypes are identified by underlying causes (see 'Introduction' above):

•Central neuropathic pain attributed to multiple sclerosis

•Central poststroke pain

●Pathophysiology – A lesion at any level of the central nervous system from the spinal trigeminal nucleus or spinal dorsal horn rostral to the cerebral cortex has the potential to cause central neuropathic facial pain. (See 'Anatomy' above.)

Mechanisms that have been hypothesized to cause central neuropathic pain include an "irritative lesion," affecting somatosensory pathways that lead to excess activity, and postdenervation sensitization, where neurons remote from the lesion site become hyperactive and hypersensitive after losing regulatory synaptic inputs. (See 'Pathogenesis' above.)

●Clinical features

•Facial pain – Central neuropathic facial pain can cause muscle pain, felt as cramping, constriction, or crushing; burning- or freezing-type dysesthesia; or circulatory-like pain (pins and needles, stings, jabs).

Internal and external stimuli can exacerbate or trigger central pain and include cold, movement, light touch, or emotional distress.

Neuropathic facial pain can be constant or intermittent and may occur spontaneously or in response to a stimulus. (See 'Facial pain' above.)

•Associated sensory loss – Central neuropathic facial pain results from central nervous system lesions that typically produce initial or persistent sensory loss. Patients frequently have hypoesthesia, anesthesia, and/or hypoalgesia associated with the pain. (See 'Sensory symptoms' above.)

•Relation to causal central lesion – Onset of central neuropathic facial pain may coincide with, or shortly follow, the return of transiently lost or impaired sensation related to a lesion affecting somatosensory pathways. However, the onset of the pain may be delayed for years after the insult. (See 'Relation to onset of pain' above.)

●Diagnosis – The diagnosis of central neuropathic facial pain is made in patients who fulfill diagnostic criteria for either central neuropathic pain attributed to multiple sclerosis or central poststroke pain. Diagnostic neuroimaging is required to identify a causal lesion, to evaluate for an acute lesion that may require cause-specific treatment, and to exclude alternative conditions. (See 'Diagnosis' above.)

●Management

•Initial treatment options – For most patients with central neuropathic facial pain, we suggest amitriptyline as initial pharmacologic therapy (Grade 2C). We use gabapentinoids for patients with an intolerance or contraindication to tricyclic antidepressants, such as those with cardiovascular disease (including stroke). (See 'Tricyclic antidepressants' above and 'Gabapentinoids' above.)

For patients with neuralgic (brief, lancinating attacks of) facial pain attributed to multiple sclerosis or stroke, we suggest carbamazepine as initial therapy (Grade 2C). This preference is based on efficacy for trigeminal neuralgia (eg, secondary trigeminal neuralgia). (See 'Carbamazepine for patients with neuralgic pain' above.)

•Alternative treatment options – We add or switch to an alternative agent for patients with an inadequate response or contraindication to initial therapy. Options include lamotrigine, duloxetine, and venlafaxine. (See 'Alternative treatments' above.)

•Refractory treatments – Neuromodulation and invasive procedures to treat central neuropathic facial pain are reserved for patients with significant disability who have failed noninvasive measures. (See 'Interventional treatment options for refractory cases' above.)

●Prognosis – Central neuropathic facial pain is a chronic, often lifelong condition that is variably responsive to treatment. Some patients respond to initial pharmacotherapy, while many others require multiple medication trials and/or long-term therapy for sustained pain relief. (See 'Prognosis' above.)