L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome

Neuropathic Orofacial Pain

Learning Objectives¹

This module outlines the following aspects of neuropathic orofacial pain conditions:

• Aetiology
• Pathogenesis
• Clinical features
• Diagnosis
• Management

Included Conditions

• Burning Mouth Syndrome

Presenter Information

Dr Amanda Phoon Nguyen
Oral Medicine Specialist
BDS (UniMelb), MRACDS (GDP), DClinDent (Oral Med) (UWA), MRACDS (OralMed), FOMAA, FPFA, FICD, FADI, MAICD, GCHL, MICDA, FDSM

• Speaker: Amanda, Oral Medicine Specialist at the University of Western Australia (UWA) dental school.

Introduction to Pain Mechanisms

Pain Duration and Nature²

• Acute Pain
  • Common in general dental practice; typically protective and resolves once the tissue injury heals.
• Chronic Pain

Transition to Chronic Pain

If a lesion does not heal properly or the nervous system fails to recover after healing, acute pain can transition into chronic, non-protective pain.

- ==Defined as pain lasting for three months or longer.==
- ==Frequent Chronic Orofacial Pain: Occurs more than 15 days per month or lasts for more than two hours a day for at least three months.==

Major Types of Pain

• Nociceptive
• Non-nociceptive
  • Somatic Pain
    • Superficial somatic (Cutaneous pain)
    • Deep somatic (Musculoskeletal pain)
  • Visceral pain
  • Neuropathic pain

Classification of Pain Types

Temporal and Clinical Patterns

• Episodic pain
• Continuous pain
• Neurovascular pain

Nociceptive Versus Neuropathic Pain

Nociceptive Pain (“Good” Pain)³

• Considered “Normal Pain” and serves a protective function.
• Occurs as a consequence of tissue injury or noxious stimuli.
• The site of injury is the source of pain.
• Pain ceases once the noxious stimuli are removed and inflammation resolves.

Neuropathic Pain (“Bad” Pain)

• Classified as chronic pain.
• Results from a lesion or dysfunction of the Peripheral Nervous System (PNS) or Central Nervous System (CNS).
• Serves no protective or reparative role.
• Pain persists after the noxious stimuli have ceased and the tissue has healed.

Clinical Definitions (ICOP 2020)⁴

• Nociception: The neural process of encoding noxious stimuli.
• Nociceptive pain: Pain arising from actual or threatened damage to non-neural tissue due to the activation of nociceptors. It involves a normally functioning somatosensory nervous system.
• Neuropathic pain: Pain caused by a lesion or disease of the somatosensory nervous system, representing an abnormally functioning system.
• Neuralgia: Pain localized in the distribution of a nerve or nerves.
• Neuritis: Inflammation of a nerve or nerves.
• Neuropathy: A disturbance of function or pathological change in a nerve. Neuritis is a specific inflammatory subtype of neuropathy.

Nociplastic Pain and Neural Pathways

Nociplastic Pain⁵

Nociplastic pain addresses cases where patients experience pain without demonstrable tissue damage or a clear lesion/dysfunction of the Peripheral or Central Nervous Systems.

• Presents like neuropathic pain but lacks demonstrable evidence of a lesion or dysfunction (e.g., clear imaging and nerve testing).

The Nociceptive Pathway⁶

1. Injury and Transduction: Nociceptive afferents respond to chemical mediators including:
   • Bradykinin
   • Serotonin
   • Prostaglandins
   • Cytokines
   • H+
2. Transmission:
   • 1st Order Neuron: Cell bodies located in the Dorsal root ganglion.
   • 2nd Order Neuron: Located in the Rexed laminae of the spinal cord; involves spinal interneurons and the ascending spinothalamic tract.
   • 3rd Order Neuron: Located within the ventral posterolateral (VPL) nucleus of the thalamus.
3. Cortical Projection: Neurons project via the posterior limb of the internal capsule to the ipsilateral postcentral gyrus (primary somatosensory cortex).

Orofacial Specifics

Pain ascends via the anterolateral trigeminal thalamic tract to the trigeminal brainstem nuclear complex (TBNC) in the spinal nucleus. Overlap in the TBNC explains referred pain between V1, V2, and V3 branches and the spread of pain.

Trigeminal Brainstem Nuclear Complex (TBNC) Structure⁷

Sensory Inputs to Trigeminal Ganglion (TG):

• V1: Skin, Nasal Mucosa, Cranial Vessels, Cornea, Conjunctiva.
• V2: Skin, Tooth, Oral Mucosa, Nasal Mucosa.
• V3: Skin, Oral Mucosa, Tooth, Temporomandibular Joint, Cranial Vessels, Jaw muscles.

Brainstem Processing:

• Aδ and C fibers travel from the TG to the Trigeminal spinal tract.
• Signals enter the Main nucleus and the Spinal nucleus (comprised of Subnucleus Oralis [Vo], Interpolaris [Vi], and Caudalis [Vc]).

Ascending Projections:

• Projection neurons ascend via the anterolateral trigeminothalamic tract to the Thalamus (Ventral posterior medial nucleus and Posterior nucleus).
• Cortical Targets: Somatic sensory cortex, Insular cortex, Cingulate gyrus, and Frontal cortex.

Components of Postsurgical Pain⁸

• Nociceptive pain: From the activation of nociceptors.
• Inflammatory pain: From the release of inflammatory mediators.
• Neuropathic pain: From the injury of nerves.

Classification of Nerve Injury (Neuropathy)⁹

1. Neuropraxia: A transient blockage of nerve conduction without alteration to the axon.
   • Often caused by direct trauma or local anesthetic injury; not visible on imaging.
2. Axonotmesis: Rupture of axons while the surrounding connective tissue of the nerve remains intact.
3. Neurotmesis: Complete rupture of the nerve trunk where both the axon and connective tissue continuity are severed.
   • Requires immediate surgical repair.

Chronicity and Sensitization

Defining Chronicity¹⁰

• General Definition: Pain lasting for more than 3 months.
• Orofacial Pain Specifics: Pain occurring on more than 15 days per month, lasting for more than 2 hours a day, for at least 3 months.

Peripheral and Central Sensitization

Neuroplasticity and Sensitization¹¹

Repeated pain exposure changes pain pathways in the brain, increasing sensitivity to future stimuli and elevating the risk of developing chronic pain through peripheral and central sensitization.

• ==Neuroplasticity: Repeated pain exposure reinforces pain pathways (like a highway), making them more sensitive.==

Mechanisms of Hypersensitivity¹²

Long-term consequences of noxious stimuli result from both central and peripheral changes. While peripheral sensitization involves reduced thresholds in skin nociceptors, central sensitization involves increased excitability of the central nervous system.

Hallmarks of Central Sensitization:

• Decreased firing threshold.
• Firing in response to non-noxious stimuli.
• Pain spread.

Key Clinical Terms:

• Hyperalgesia: Exaggerated responses to noxious stimuli.
• Example: Extreme pain from a standard local anesthetic injection.
• Allodynia: Pain sensitivity to normally non-noxious mechanical and thermal stimuli.
• Examples: Wind blowing across the face, shaving, or brushing teeth.

The ‘Wind-Up’ Phenomenon¹³

• Repetitive noxious stimulation of primary C-fiber afferents leads to an escalation of nociceptive transmission in the dorsal horn.
• Wide-dynamic range neurons are recruited, resulting in the amplification and prolongation of nociceptive transmission in ascending CNS pathways.
• Central sensitization is primarily mediated via the activation of the N-methyl-D-aspartate (NMDA) glutamate receptor.

Epidemiology and Prevalence

General Prevalence Data¹⁴

• General Community: > 2% prevalence of neuropathic pain.
• Cancer Patients: One-third experience neuropathic pain (either alone or in combination with nociceptive pain).
• Low Back Pain: > 50% of patients have an associated neuropathic component.

Trigeminal Nerve Injury Incidence¹⁵

The incidence of neuropathic pain following injury to peripheral branches of the trigeminal nerve (due to implants, 3rd molar extractions, orthognathic surgery, mid-face fractures, or root canal therapy) is estimated at 3-5% (IASP 2016).

• ==Post-Dental Treatment Specifics: Third molar surgery is noted as the most common cause of these injuries.==
• ==Local Anesthetic Injections: These are also identified as a potential cause of trigeminal nerve injury leading to neuropathic pain.==

Posttraumatic Neuropathy¹⁶

Research regarding the profiling of patients presenting with posttraumatic neuropathy of the trigeminal nerve, specifically following third molar surgery (Renton & Yilmaz, 2011).

Risk Groups¹⁷

Chronic pain can affect anyone.

The Biopsychosocial Model of Pain

Components of the Biopsychosocial Model¹⁸

• Biological (Bio): Partial genetic susceptibility and biological pain processes.
• Psychological (Psycho): Perpetuating psychological factors.
  • ==Catastrophizing: Thinking of the worst-case scenario.==
• Social: Life stressors, work claims, access to care, sleep quality, alcohol use, smoking, and other comorbid pain conditions.
  • ==Work Cover Claims: Patients with active claims often have a poorer prognosis due to the associated stress of the legal/financial process.==

Dual Axis Assessment¹⁹

• Axis I: Somatosensory Input (Acute pain focus).
• Axis II: Psychosocial Input (Chronic pain focus).

Over time, the interaction of these axes leads to suffering and observable pain behavior. Identifying these risk factors helps in predicting the transition from acute to chronic pain.

Axis Dominance

In chronic pain, Axis 2 factors become more dominant over time, impacting suffering and pain behavior.

Pain Vulnerability Predictors

Risk Factors for Pain Vulnerability²⁰

• Female gender
• Stress and Anxiety
• Neuroticism
• Catastrophizing
• Presence of comorbid chronic pain conditions

Chronic Overlapping Pain Conditions

• Fibromyalgia
• Chronic Fatigue Syndrome
• Chronic Migraine
• Chronic Tension-Type Headache
• Interstitial Cystitis
• Irritable Bowel Syndrome
• Chronic Low Back Pain
• Vulvodynia
• Endometriosis
• Temporomandibular Disorders (TMD)

Clinical Case Studies in Mismanagement

Clinical Consequences of Dentoalveolar Pain Mismanagement²¹

What are the clinical consequences of the mismanagement of dentoalveolar pain?

Progression of Invasive Dental Interventions²²

Online, the patient found a prosthodontist (dentist no. 3) who examined her approximately two months after her initial root canal treatment (RCT). By tapping on tooth 21, he determined her responses indicated a dentoalveolar pain (DAP) problem and referred her to a periodontist (dentist no. 4). This led to a series of evaluations by these two dentists and three other colleagues within two dental group practices:

• Tooth 21: Dentist no. 4 concluded the tooth was cracked and extracted it; an immediate implant was placed. A temporary crown was later placed by dentist no. 3.
• Tooth 22: Because pain persisted, an endodontist (dentist no. 5) performed an RCT. When pain worsened, extraction was recommended based on a diagnosis of a cracked root by a second periodontist (dentist no. 6) and endodontist (dentist no. 7). An implant was placed and remains in situ.
• Implant Removal: Due to questionable radiographic findings at the tip of the implant for tooth 21, that implant was removed.

Diagnostic Failures and Specialist Consultations

Throughout this three-year span, the patient’s symptoms steadily worsened. None of the seven dentists mentioned an alternative diagnosis to toothache or cracked root, nor did they suggest consulting an orofacial pain (OFP) specialist, oral medicine specialist, or physician.

Eventually, the patient sought an opinion at the Mayo Clinic. Within 30 minutes, a diagnosis of atypical odontalgia (a neuropathic pain problem) was offered. Initial treatment with gabapentin was unsuccessful, leading the patient to seek further opinions across the country:

• Neurology: One neurologist suggested microvascular decompression for trigeminal neuralgia, while another warned against it.
• Oral Surgery: Surgeons in the Midwest recommended surgical excavation of the dentoalveolar bone for suspected neuralgia-inducing cavitational osteonecrosis (NICO).

Long-term Management and Outcomes

The patient was advised by the article’s author to avoid the NICO procedure. Management strategies included:

• Topical Medication: An oral stent with a custom mixture of pregabalin, cortisone, and lidocaine provided moderate, temporary relief.
• Systemic Medication: A series of neuropathic pain medications were tried with limited success.
• Pain Management: After failing to improve with stellate ganglion blocks for a suspected sympathetically maintained pain disorder, she was prescribed daily opioid medications combined with other centrally acting drugs.

Legal and Professional Implications

The patient consulted an attorney regarding a malpractice suit. While the initial treatments by dentists no. 1 and no. 2 were deemed acceptable collaborations for vague symptoms, a suit was brought against the subsequent five dentists. The claim focuses on the failure to consider nonodontogenic diagnoses and the cycle of invasive procedures (extractions and implants) performed over the following six years. The outcome of this action is pending.

Case 2: 27-Year-Old Woman²³

• Desired to continue searching for a provider to correct her occlusal problem or eliminate pain without using centrally acting drugs.
• Demonstrated nonacceptance of a working diagnosis of neuropathic pain.

Clinical History^24252627

The patient recalled her initial problem as pain in the maxillary right arch, specifically in the premolar area, approximately five years earlier.

Sequential Dental Treatments

• Initial Treatment: Her general dentist attributed the pain to pulpal inflammation of the first premolar and performed endodontic treatment.
• Subsequent Interventions: After brief improvement, the pain reappeared. The dentist attributed this to sensitivity in nghboring teeth and proceeded with additional sequential root canal treatments (RCTs) as the pain migrated from one tooth to another.

How many?

Persistent Idiopathic Dentoalveolar Pain

Clinical Progression and Symptoms²⁸

After these extensive procedures, her overall pain increased, with alternating periods of slight remissions and worsening episodes. The patient described the pain as feeling like an electrical stimulus that is never too intense but sometimes reaches 7 of 10 on a numeric rating scale.

The location of the pain was variable from time to time, primarily in the original quadrant but also migrating to the other quadrants. The patient was not able to identify any particular trigger for the pain but described some occasional associated symptoms, such as:

• A burning sensation in the gingiva
• A bad taste in the mouth
• Headaches with a frequency of no less than 7 days per month

Treatment Proposals and Outcome

Prosthetic treatment was proposed to adjust her occlusion and exclude any cause for pain related to misalignment of the teeth. Time passed without any improvement, and her dentist suggested an escalation to a third step of treatment: full-mouth extractions and provision of an implant-supported prosthesis.

At that point the patient, frightened over the prospect of this extensive proposed surgical intervention, decided to ask for a second opinion, 5 years after the first appointment with the first dentist. The patient never returned for a second consultation and communicated that she would instead continue her search for someone who might be able to correct her occlusal problem or to make her pain disappear without any centrally acting drugs.

Post-Traumatic Trigeminal Neuropathic Pain

Previous Terminology²⁹

• Anaesthesia dolorosa
• Painful post-traumatic trigeminal neuropathy
• Persistent dentoalveolar pain
• Deafferentation pain
• Phantom tooth pain
• Atypical odontalgia
• Atypical facial pain

Definition and Characteristics

Unilateral or bilateral facial or oral pain following and caused by trauma to the trigeminal nerve(s), with other symptoms and/or clinical signs of trigeminal nerve dysfunction and persisting or recurring for more than 3 months.

• ICOP Criteria: Pain developing within six months of a traumatic event to the trigeminal nerve
• Duration: Pain persists for more than three months

Post-traumatic trigeminal neuropathic pain rarely, if ever, crosses the midline but, over time, it may in some cases become more diffusely distributed.

Epidemiology and Clinical Presentation

Epidemiological Factors³⁰

• Rare condition
• Good estimates of the prevalence of PTTN are lacking, possibly due to shifting diagnostic terms and criteria
• Traumatic injuries to the trigeminal nerve only rarely lead to a painful neuropathy
• Onset usually occurs in middle age (40-50 years)
• More common in females
• Associated with significant psychosocial stressors

Diagnostic Criteria³¹

• Oral or facial pain developing within 6 months of an identifiable traumatic event to the trigeminal nerve
• The pain persists beyond the normal healing time
• Usually unilateral and localised to the distribution of the trigeminal nerve

Symptom Characteristics

• Quality: Often burning or shooting
• Associated Sensations: Swollen or foreign body sensation, heat or cold, or redness/flushing
• Intensity: Moderate to severe
• Duration: Often continuous, but may be paroxysmal or mixed
• Clinical Signs: May include hyperalgesia, allodynia, hypoaesthesia, or hypoalgesia

Case Study: Foreign Body Sensation

A patient reported feeling a "fishbone" in her tongue for 10 years despite no physical object being present, illustrating the "foreign body" sensation common in PTTN.

Management Strategies³²

General Principles³³

• Avoid irreversible dental treatment if an obvious dental cause cannot be identified
• Often difficult to manage once established
• Minimise pain and inflammation around the time of injury/surgery (consider pre, peri, and post-operative adequate anesthesia)

Therapeutic Approaches

• Pharmacologic:
  • Topical: e.g., local anaesthetics, capsaicin
  • Systemic: e.g., tricyclic antidepressants, gabapentinoids, anticonvulsants, selective noradrenaline reuptake inhibitors
• Psychological: Cognitive behavioural approaches
  • Mindfulness
  • Prognosis: A 50% reduction in pain is considered a clinical success; 100% cure is rare.
  • Referral Timing: Referral after 12 months significantly reduces the chance of improvement.

Pharmacological Management Table³⁴

Drug Class	Mechanism of Action	Active Ingredient	Daily Dose
Tricyclic antidepressants (TCAs)	Inhibit the reabsorption (reuptake) of serotonin and norepinephrine	Amitriptyline	10-200 mg
Phenothiazines	Block dopamine D2 receptor	Chlorpromazine	60-300 mg
Beta-blockers	Block the effects of epinephrine (adrenaline)	Propranolol	5-50 mg
Anticonvulsants	Intervene on the Ca2+ canal	Gabapentin	300-3600 mg
		Pregabalin	300-600 mg
		Clonazepam	1-10 mg
Agonist of GABA receptor	Acts on the CNS to produce muscle relaxant effects	Baclofen	30-200 mg
Topical medications	Encourages release and inhibits biosynthesis/transport of substance P	Capsaicin	0.025% topical
Minor opiate analgesics	Relieve pain in the CNS	Tramadol / Codeine	100-400 mg

Renton, Dawood, Shah, Searson & Yilmaz, 2012

Summary Points from Research³⁵

• Patients were aware of signing consent forms for surgery in 11 cases, but 8 of those felt they were not explicitly warned about nerve injury.
• Over 70% of patients were referred more than six months post-injury.
• Imaging used included CBCT (10%), dental pantomograph (50%), and long cone periapical radiographs (48%). However, no radiographic evidence was present pre- or postoperatively in 15% of cases.
• Permanent IAN neuropathy was sustained in 27 patients.
• 3 patients achieved resolution of neuropathy after removal of the implant within 30 hours of placement.

Persistent Idiopathic Facial Pain

Overview and Terminology³⁶

• Alternative Nomenclature: Previously known as atypical facial pain or phantom toothache.
• Classification: Atypical Odontalgia (AO) may be considered a subform of Persistent Idiopathic Facial Pain (PIFP).
• Clinical Nature: Persistent oral and/or facial pain with varying presentations, occurring in the absence of clinical neurological deficit.
• Pain Pattern: Characterized by daily (or near daily) pain that may spread to different locations.
• Relationship to Other Conditions: May be part of a continuum with Post-traumatic Trigeminal Neuropathic Pain (PTTN).

Epidemiology and Comorbidities³⁷

• Prevalence: Rare.
• Demographics: Onset usually occurs in middle age, with a female predominance.
• Central Sensitivity: Associated with central sensitivity syndrome, including comorbidities such as:
  • Chronic widespread pain
  • Fibromyalgia
  • Irritable bowel syndrome
• Psychosocial Factors: Associated with high levels of psychiatric comorbidity and psychosocial disability.

Diagnostic Criteria and Presentation

Localization and Onset³⁸

• Localization: Oral and/or facial pain that is poorly localized and does not follow the distribution of a peripheral nerve.
• Duration: Pain persists beyond the normal healing time.
• Spread: The pain is initially confined but may subsequently spread in a non-dermatomal pattern.
• Etiology: Onset of symptoms may not necessarily be associated with a physically traumatic event.
• Examination: Clinical neurological examination is normal.

Symptom Characteristics³⁹

• Variability: Symptoms vary considerably between patients.
• Quality: Often dull, aching, or nagging; sometimes presents with sharp exacerbations, though other pain qualities may be described.
• Intensity: Ranges from mild to severe.
• Frequency: Often continuous and recurs daily.
• Exacerbating Factors: Aggravated by stress.
• Associated Conditions: Often co-exists with other chronic orofacial pain or headache.
• Dental Findings: No dental cause identified.

ICHD-3 Diagnostic Criteria⁴⁰

1. Pain Presentation: Facial and/or oral pain fulfilling criteria 2 and 3.
2. Frequency and Duration: Recurring daily for >2 hours/day for >3 months.
3. Pain Characteristics: Must include both of the following:
   • Poorly localized and not following the distribution of a peripheral nerve.
   • Dull, aching, or nagging quality.
4. Neurological Status: Clinical neurological examination is normal.
5. Exclusion of Dental Cause: A dental cause has been excluded by appropriate investigations.

Diagnosis of Exclusion

PIFP is primarily a diagnosis of exclusion, often requiring the ruling out of all other potential causes before confirmation.

6. Differential Diagnosis: Not better accounted for by another ICHD-3 diagnosis.

Management Strategies⁴¹

• Complexity: This condition is difficult to manage.
• Care Setting: Usually requires management by pain specialists in a multidisciplinary setting.
• Treatment Modalities:
  • Pharmacological Therapy: Including tricyclic antidepressants, gabapentinoids, anticonvulsants, and selective noradrenaline reuptake inhibitors (SNRIs).
  • Psychological Support: Cognitive behavioral therapy (CBT) and psychotherapy.

Trigeminal Neuralgia

Definition and Overview⁴²

• Other names: Tic douloureux.
• A severely painful disorder characterised by brief electric shock-like pain in the distribution of the trigeminal nerve, triggered by innocent stimuli.

Epidemiology

• Uncommon.
• Typically affects middle to old age.
• More common in females.

Clinical Consideration

• Is this a trigeminal neuropathy?

Aetiopathogenesis and Diagnosis

Classification of Trigeminal Neuralgia⁴³

• Classical Trigeminal Neuralgia: Neurovascular conflict at the trigeminal nerve root entry zone
  • Classical cases are often caused by the superior cerebellar artery compressing the nerve.
• Secondary Trigeminal Neuralgia: Space-occupying lesion, multiple sclerosis, or other abnormality
  • Secondary causes include underlying diseases like Multiple Sclerosis or tumors.
• Idiopathic Trigeminal Neuralgia: No obvious cause
  • In idiopathic cases, symptoms are present without an identifiable cause on MRI.

Pathophysiology

• Trigeminal nerve root atrophy (demyelination) and/or displacement leading to ectopic firing of neurons.

Clinical Presentation⁴⁴

• Recurrent severe paroxysmal pain in one or more divisions of the trigeminal nerve.
• Usually unilateral.
• Quality: Electric shock, shooting, stabbing, sharp.
• Duration: Usually lasts a fraction of a second.
• Triggers: Triggered by innocuous stimuli (e.g., light touch, talking, chewing).
• Can present with concomitant background pain between the attacks.
• Patients typically feel completely normal between the brief episodes of pain.

Related Conditions

• These clinical features can also occur in the distribution of other sensory nerves (e.g., glossopharyngeal neuralgia, occipital neuralgia).

Diagnostic Process⁴⁵

• Primarily a clinical diagnosis.
• Investigations: MRI to assess for underlying causes.

Red Flags and Atypical Presentations

Atypical presentations may suggest other pathology and require specialist assessment, including:

• Bilateral pain in a younger patient.
• Involvement of multiple cranial nerves.
• Coexisting sensory or motor disturbances.

Pharmacologic Management⁴⁶

• First-line therapy: Carbamazepine.
• Adverse effects: Risk of severe reactions, such as Stevens-Johnson Syndrome and bone marrow depression

Genetic Screening

Patients of Asian descent should be screened for the HLA-B 1502 allele before starting Carbamazepine to avoid Stevens-Johnson Syndrome or bone marrow suppression. .

• Other medications: Anticonvulsants, gabapentinoids, and baclofen.

Neurosurgical Interventions

• Microvascular decompression.
  • This involves placing a Teflon sheet between the nerve and the compressing artery.
• Rhizotomy.
• Balloon compression.
• Gamma knife.

Trigeminal Post-Herpetic Neuralgia

Overview and Definition⁴⁷

• Other names: Post-herpetic trigeminal neuropathy
• Definition: Unilateral neuropathic facial pain in the distribution of the trigeminal nerve caused by herpes zoster.
• Duration: The condition can persist for months to years.
• Prevalence: 25-50% of patients over 50 years of age with herpes zoster develop post-herpetic neuralgia (PHN), defined as pain persisting for three months or more after the healing of the rash.

Risk Factors⁴⁸

Key risk factors for developing post-herpetic neuralgia include:

• Over 60 years of age.
• Severe herpes zoster rash.
• Severe pain during the initial herpes zoster infection.
• Immunocompromised status.
• Ophthalmic involvement.

Clinical Presentation⁴⁹

• Distribution: Unilateral facial pain occurring in the same trigeminal nerve branch(es) as the original herpes zoster infection. It most commonly affects the ophthalmic division of the trigeminal nerve.
• Pain Quality: Burning or itching sensation.
• Intensity: Moderate intensity.
• Temporal Pattern: Pain may be continuous or may occasionally present as intermittent shooting or electric shock-like attacks.
• Sensory Changes: Presence of allodynia and hyperalgesia.

Management and Prevention⁵⁰

Trigeminal post-herpetic neuralgia is difficult to manage. Strategies include:

• Prevention:

  • Treating herpes zoster early to reduce the risk of developing PHN.
  • Vaccination of adults over 50 years of age to minimize varicella zoster virus reactivation.

• Topical Therapy:

  • Capsaicin (caution is required near the eyes).
    • Capsaicin (Zostrix)
  • Lidocaine.

• Systemic Therapy:

  • Gabapentinoids.
  • Tricyclic antidepressants.
  • Serotonin-noradrenaline reuptake inhibitors (SNRIs).

Oral Burning and Burning Mouth Syndrome⁵¹

Oral Burning

Case Study: “Jane”⁵²

• 55-year-old female who presents with a 4-month history of oral burning.
• Constant, predominantly affecting her dorsal tongue, and she feels that it is gradually getting worse.
• Medical History: Type 2 diabetes, asthma, gastroesophageal reflux, hypertension, depression, and anxiety.
• Daily medications: Metformin, warfarin, escitalopram, pantoprazole, ramipril, fluticasone puffer.
• Social History: Never smoker, 1–2 standard alcoholic beverages per week.

Clinical Considerations⁵³

• What are the possible causes of oral burning?
• What are the most common causes?
• Is it Burning Mouth Syndrome (BMS)?
• Is BMS the best name for it? (Nomenclature)

Associated Symptoms

Subjective xerostomia, dysaesthesia, and dysgeusia (altered taste) are present in two-thirds of reported cases.

Differential Diagnosis of Oral Burning⁵⁴⁵⁵

Etiology of Oral Burning⁵⁶

• Idiopathic: E.g., Burning Mouth Syndrome, Oral Dysaesthesia
• Infective: E.g., Candidosis, Viral
• Degenerative: E.g., Alzheimer’s
• Systemic: E.g., Nutritional Deficiencies, Hematinic Deficiencies, Hormonal Changes, Age-Related Changes, Renal Problems, Psychiatric Issues
• Metabolic: E.g., Diabetes, Thyroid Dysfunction
• Iatrogenic: E.g., Medication Related
• Traumatic (Iatrogenic): E.g., Radiotherapy, Surgery
• Neoplastic: E.g., CNS Pathology
• Autoimmune: E.g., Sjogrens
• Immune-Mediated: E.g., Oral Mucosal Diseases such as Oral Lichen Planus
• Traumatic: E.g., Damage from causes such as GORD/Anorexia, Dehydration

Possible causes of oral burning include:

• Medication related (most common)
• Traumatic, including iatrogenic causes (e.g., radiotherapy to the oral cavity), or physical, thermal, or chemical trauma
• Autoimmune/immune mediated (e.g., Sjogren’s syndrome or oral lichen planus)
• Neoplastic (e.g., central nervous system pathology)
• Idiopathic (e.g., oral dysaesthesia or BMS)
• Infective (e.g., oral candidosis)
• Degenerative (e.g., Alzheimer’s disease)
• Systemic conditions (e.g., nutritional deficiencies)
• Metabolic conditions (e.g., diabetes)

Diagnostic Considerations⁵⁷

• Investigations must be thorough.
• Consider a range of systemic and local factors.
• Specific considerations for the case study include:
  • Jane’s medications, diabetic control, asthma, and hypertensive control.
  • Nutritional deficiencies and diet.

Clinical Assessment and Investigations

History Taking Elements⁵⁸

It is important to seek a history of the oral burning, including:

• Symptoms and date of onset
• Precipitating event
• Previous treatments trialled and other investigations undertaken
• Quality of the pain and intensity of the symptoms
• Exacerbating or relieving factors

Medication-Related Adverse Effects⁵⁹

Extensive lists of medications can cause oral burning, including:

• Antihypertensives
• Antibiotics
• Neurological medications
• Cardiac medications
• Endocrine medications
• Psychotropic medications

Most commonly implicated: ACE inhibitors and angiotensin receptor blockers.

Supplement-Related Effects⁶⁰⁶¹⁶²

• Vitamin B₆ (Pyridoxine): Doses ≥200 mg/day have been associated with severe sensory peripheral neuropathies. Risk often arises from multiple products being taken simultaneously.
• Zinc: Often associated with altered or impaired taste and smell. Intranasal zinc can cause anosmia. Doses ≥80 mg/day in clinical trials were associated with adverse prostate effects.
• ArmaForce (Andrographis): Known TGA warning for causing taste changes, specifically a metallic or soapy taste.

Psychosocial History⁶³⁶⁴

• Psychological and psychiatric comorbidities are more prevalent in patients experiencing oral burning.
• Some patients have a high incidence of anxiety, depression, and personality disorders.

No supplements, no diet changes.

Dental History and Examination⁶⁵

• Associated symptoms: Xerostomia, salivary gland hypofunction, dysaesthesia, and dysgeusia.
• Trauma history: Chemical, mechanical, or thermal trauma.
• Parafunctional habits: Tongue thrusting.
• Mucosal lesions/diseases:
  • Oral infections (e.g., oral candidosis)
  • Mucocutaneous lesions (e.g., oral lichen planus)
  • Hypersensitivity, contact allergy, and lichenoid reactions

Clinical Findings for Jane⁶⁶⁶⁷⁶⁸

• Prosthetics: Partially edentulous; wears a full upper denture (>10 years old, poorly fitting). Rarely removes it at night.
• Hygiene/Habits: Does not rinse mouth after steroid puffer use.
• Intraoral Exam: Creamy, semi-adherent plaques in the maxillary buccal sulcus. The rest of the extraoral and intraoral examination is unremarkable.
• Neurological: Cranial nerve (CN) exam reveals no remarkable findings.

Creamy, semi-adherent plaques in the maxillary buccal sulcus (Oral Candidiasis).

Based on her history and exam, what would be the most likely diagnosis?

What further tools or investigations would be helpful in establishing the cause of her oral burning?

Further Investigations⁶⁹

• Serology and saliva testing (with limitations).
• Assessment for objective salivary gland hypofunction.

Saliva Testing

Saliva testing is generally considered unreliable and is not recommended for the routine diagnosis of oral burning.

Consider testing for:

• Nutritional abnormalities (e.g., vitamin B12, folic acid, or iron deficiencies)
• Diabetes mellitus
• Hormonal deficiencies

Blood Tests⁷⁰

• Standard Panel: FBC, iron studies, serum folate, and vitamin B12 levels.
• Additional Vitamins: B1, B2, B6, and zinc (though strong associations are not always shown).
• Metabolic/Endocrine: HbA1c; Thyroid function test (if clinically indicated).
• Autoimmune Serology: Investigations for Sjogren’s syndrome and systemic lupus erythematosus.

Case Progress⁷¹

• Jane’s results for FBC, iron studies, vitamin B12, serum folate, and glycated haemoglobin are all within normal limits.
• Assuming there are no signs of other systemic conditions, no cranial nerve abnormalities, and no oral pathology or mucosal lesions, what could her diagnosis be?

Burning Mouth Syndrome Definition and Criteria⁷²

Definition and Terminology⁷³

• BMS: Also known as oral dysaesthesia or complex oral sensitivity disorder.
• Older terminology: ‘Stomatodynia’, ‘glossopyrosis’, or ‘glossodynia’.
• Classifications: Types 1, 2, 3; primary and secondary.
• Nature of Diagnosis: It is a diagnosis of exclusion.
• Characteristics: Defined as a chronic intraoral burning sensation with no identifiable local or systemic cause. Clinical signs and laboratory findings appear “normal,” though intensity can fluctuate.

Epidemiology and Pathophysiology⁷⁴

• Prevalence: Affects between 0.1% and 3.9% of the general population.
• Demographics: Can affect anyone, but more common in postmenopausal women.
• Hypothesized Causes: Poorly understood; theories include peripheral neuropathy or neuropathic pain with central sensitisation.
• Observations: Patients show varying levels of changes in somatosensory function.

ICOP Diagnostic Criteria (6.1)⁷⁵

An intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day for more than 3 months, without evident causative lesions on clinical examination and investigation.

Criteria:

1. Oral pain fulfilling criteria 2 and 3.
2. Recurring daily for >2 hours per day for >3 months (if less, classified as probable BMS).
3. Pain has both a burning quality and is felt superficially in the oral mucosa.
4. Oral mucosa is of normal appearance, and local/systemic causes have been excluded.
5. Not better accounted for by another ICOP or ICHD-3 diagnosis.

How is burning mouth syndrome (BMS) treated?

Management of Burning Mouth Syndrome

Management Principles⁷⁶

• Expectations: Need to be conscious of patient expectations and the effect on quality of life.
• Nature: Chronic condition; management may be difficult.
• Psychosocial Factors: Needs consideration of any perpetuating factors.
• Referral: Typically referred to an oral medicine specialist or appropriate specialist for multidisciplinary management (e.g., psychological support).

Pharmacotherapy⁷⁷

Various pharmacological treatments have been trialled with varying success rates:

• Topical or systemic clonazepam
  • Topical Clonazepam: 0.5mg tablet sucked and spat out 3x daily (Note: Risk of addiction/drowsiness).
• Gabapentinoids
• Tricyclic antidepressants
• Antispasmodics

Other Treatment Modalities⁷⁸

• Vitamin B12 or zinc supplementation
• Alpha-lipoic acid
  • Alpha Lipoic Acid: Functions as an antioxidant supplement.
• Palmitoylethanolamide
  • Palmitoylethanolamide (PEA): Acts as a glial cell modulator.
• Low-level laser therapy
• Capsaicin mouthwashes
  • Capsaicin Mouthwash: Can involve using diluted Tabasco sauce to deplete TRPV1 receptors.

Management remains challenging as few highly effective treatments are available.

Mechanism of Capsaicin in BMS⁷⁹

• TRPV1 Up-regulation: Studies show up-regulation of TRPV1-positive nerve fibres in the tongue mucosa of BMS patients.
• Receptor Function: The vanilloid receptor-1 (TRPV1) is a cation channel on unmyelinated C-nociceptive nerve fibres, activated by capsaicin, heat, and H+.
• Desensitization: Capsaicin binds to TRPV1, causing depolarization. Prolonged activation depletes pre-synaptic substance P, making the neurons less likely to report pain.

Dysperceptions in Patients with BMS (Adamo et al. 2023)⁸⁰⁸¹

• Burning
• Intraoral Foreign Body Sensation
• Xerostomia
• Dysgeusia
• Globus pharyngeus
• Subjective change in tongue morphology
• Sialorrhea
• Itching
• Tingling sensation
• Occlusal Dysesthesia
• Oral dyskinesia
• Dysosmia
• Subjective Halitosis

Case Study: Foreign Body Impaction⁸²

• Patient Profile: Middle-aged female.
• Case Description: Referred due to an inability to remove a foreign object stuck between teeth for five years.
• Diagnosis: Foreign body impaction (Fish bone).
• Clinical Features:
  • Chronic foreign body sensation.
  • Inability to floss.
  • Referred pain/sensation.
• Examination Findings: Porcelain fused to metal (PFM) crown/bridge.

Case Study: Suspected Occlusal Dysesthesia

• Patient Profile: Middle-aged male.
• History: Referred by an orthodontist; patient requested a third round of fixed orthodontics.
• Subjective Findings: Suspected hallmarks of occlusal dysesthesia.
• Investigations Conducted:
  • OC Top
  • OC Bottom
  • Occlusal radiograph

Phantom Bite Syndrome

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Audio Appendix

Additional Audio Content

The following sections from the lecture audio did not correspond to any heading in the main document.

Phantom Bite Syndrome (Occlusal Dysesthesia)

• Characteristics: A sustained delusion that the “bite” is wrong, often following a minor dental procedure.
• Patient Profile: Often high socioeconomic status, high-functioning, and possesses significant dental knowledge.
• Clinical Signs: Patients may bring “bags of splints” or multiple study models and have seen numerous dentists.
• Management: Extremely difficult; requires psychiatric referral as it overlaps with body dysmorphic disorder. Irreversible dental “adjustments” typically worsen the condition.

Case Study: 27-Year-Old Woman (Sequential Treatments)

• History: Patient had pain in the maxillary right premolar area for five years.
• Clinical Progression:
  • The dentist performed sequential root canals as pain “migrated” from tooth to tooth.
  • Total Treatment: The dentist performed 28 root canals and crowned all treated teeth.
  • Proposed Treatment: Full mouth extractions and implant-supported prosthesis.
• Symptoms: Electrical sensations, burning gingiva, bad taste, and headaches.
• Outcome: The patient had pre-existing neuropathic pain but sought a dental “fix” to avoid centrally acting medications.

Case Study: The Tissue Box Injury

• History: A middle-aged woman was hit in the face by a box of facial wipes. She developed localized pain in the 21/22 region.
• Mismanagement:
  • Dentist 1: Found no pathology but referred to an endodontist.
  • Dentist 2 (Endodontist): Performed a root canal on a vital tooth (21). Pain increased.
  • Dentist 3 (Prosthodontist) & Dentist 4 (Periodontist): Misdiagnosed a “cracked tooth,” extracted 21, and placed an implant. Pain persisted.
  • Dentist 5 (Endodontist): Performed a root canal on 22.
  • Dentist 6 (Periodontist) & Dentist 7 (Endodontist): Extracted 22 and placed another implant.
• Outcome: After three years and seven dentists, the patient was finally diagnosed with neuropathic pain. She sued all practitioners except Dentist 1 and the first endodontist.

Case Study: “Jane”

• Profile: 55-year-old female with constant burning on the dorsal tongue.
• Medical History: Type 2 diabetes, hypertension, depression, anxiety, and GERD.
• Clinical Findings: Pseudo-membranous candidosis (likely from a steroid puffer).
• Progression: Burning persisted even after the candidosis was successfully treated.

Case Study: Suspected Occlusal Dysesthesia

• A patient with dentures insisted her “poor bite” was causing her face to tilt and her clothes to fall off. Despite four sets of dentures made by specialists, the sensation persisted.

Case Study: Foreign Body Impaction

• A patient insisted something was stuck between her teeth; no physical object was found. This was a manifestation of oral dysesthesia.

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