# Neuropathic Orofacial Pain ## including ### Burning Mouth Syndrome **Outline the aetiology, pathogenesis, clinical features, diagnosis and management of neuropathic orofacial pain conditions.** These lecture slides and associated module materials must not be reproduced, distributed or shared without prior permission. Unauthorised use of this material breaches UWA’s student conduct regulations and may also constitute a violation of the Copyright Act 1968. **Dr Amanda Phoon Nguyen** BDS (UniMelb), MRACDS (GDP), DClinDent (Oral Med) (UWA), MRACDS (OralMed), FOMAA, FPFA, FICD,FADI, MAICD, GCHL, MICDA, FDSM **Oral Medicine Specialist** #### Learning Objectives 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 Is all pain the same? Acute Pain Chronic Pain Major Types of Pain Nociceptive Non-nociceptive Somatic Pain Visceral pain Neuropathic pain Superficial somatic Deep somatic Episodic pain Continuous pain Cutaneous pain Musculoskeletal pain Neurovascular pain <p>Forms an island surrounding a figure</p>   #### Pain Duration and Nature - **Acute Pain** - **Chronic Pain** #### Major Types of Pain - **Nociceptive** - **Non-nociceptive** - Somatic Pain - Superficial somatic (Cutaneous pain) - Deep somatic (Musculoskeletal pain) - Visceral pain - Neuropathic pain #### Temporal and Clinical Patterns - Episodic pain - Continuous pain - Neurovascular pain A figure comparing Acute Pain and Chronic Pain using a railroad track metaphor. On the left, 'Acute Pain' is depicted with a short, steep roller coaster track leading to a heart with a bandage, symbolizing a sudden but brief event. On the right, 'Chronic Pain' is shown as a long, winding track extending into the distance, accompanied by lightning bolts, representing prolonged and persistent discomfort. A hierarchical diagram titled 'Major Types of Pain', starting with a flame icon at the top. It branches into 'Nociceptive' and 'Non-nociceptive'. Nociceptive further divides into Somatic Pain (subdivided into Superficial somatic -> Cutaneous pain; Deep somatic -> Musculoskeletal pain) and Visceral pain. Non-nociceptive includes Neuropathic pain (highlighted in a blue oval), which leads to Neurovascular pain. Arrows connect these categories to anatomical illustrations: a hip joint for musculoskeletal pain and a tooth for neurovascular/cutaneous pain. “Good and Bad” Pain ## Nociceptive Pain • “Normal Pain” / protective • Consequence of tissue injury or noxious stimuli • Site of injury = source of pain • When noxious stimuli is removed, inflammation resolves and pain ceases ## Neuropathic Pain • Chronic pain • Lesion / dysfunction of the PNS or CNS • No protective or reparative role • Pain persist after noxious stimuli has ceased and tissue healed #### Nociceptive Pain ("Good" Pain) - 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. • **N**ociception: The neural process of encoding noxious stimuli. • **Nociceptive pain:** Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors. Normally functioning somatosensory nervous system • **Neuropathic pain:** Pain caused by a lesion or disease of the somatosensory nervous system. Abnormally functioning somatosensory nervous system • **Neuralgia:** Pain 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 special case of neuropathy, the term being reserved for inflammatory processes affecting nerves. ICOP 2020 #### Clinical Definitions (ICOP 2020) - **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. # Is there something missing? What happens if someone has pain but there is no demonstrable tissue damage or lesion / dysfunction of the PNS or CNS? **NOCIPLASTIC PAIN** Is there something missing? #### Nociplastic Pain Nociplastic pain addresses cases where patients experience pain without demonstrable tissue damage or a clear lesion/dysfunction of the Peripheral or Central Nervous Systems. Injury<br> Transduction<br> Nociceptive afferents<br> Bradykinin<br> Serotonin<br> Prostaglandins<br> Cytokines<br> H+<br> Dorsal root ganglion<br> 1st order neuron<br> Transmission<br> Spinal interneuron<br> Ascending pathway<br> Spinothalamic tract to the ventral posterolateral (VPL) nucleus of the thalamus<br> 3rd order neurons lie within the VPL of the thalamus.<br> They project via the posterior limb of the internal capsule to terminate in the ipsilateral postcentral gyrus (primary somatosensory cortex)<br> 2nd order neurons<br> Rexed laminae of the spinal cord  #### The Nociceptive Pathway 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). Labelled anatomical diagram illustrating the pain pathway. The visual flow starts on the left with a hand receiving an injury (hammer icon), labeled 'Injury' and 'Transduction'. Chemical mediators released at the site are listed: Bradykinin, Serotonin, Prostaglandins, Cytokines, H+. The pathway continues to a blue neuron cell body labeled 'Nociceptive afferents', which connects via yellow lines to the central structure. A blue globe-like icon is labeled 'Dorsal root ganglion' and '1st order neuron'. The central component depicts a cross-section of the spinal cord showing 'Spinal interneuron' and '2nd order neurons' located in the Rexed laminae. The path extends rightward as the 'Ascending pathway' or 'Spinothalamic tract', leading to a multi-colored brain model representing the '3rd order neurons' in the thalamus and their projection to the primary somatosensory cortex. ```mermaid graph TD %% Sensory Inputs V1[V1: Skin, Nasal Mucosa, Cranial Vessels, Cornea, Conjunctiva] --> TG[Trigeminal ganglion] V2[V2: Skin, Tooth, Oral Mucosa, Nasal Mucosa] --> TG V3[V3: Skin, Oral Mucosa, Tooth, Temporomandibular Joint, Cranial Vessels, Jaw muscles] --> TG %% Trigeminal Nerve to Brainstem TG -- "Aδ and C fibers" --> TST[Trigeminal spinal tract] TST --> MN[Main nucleus] TST --> SN[Spinal nucleus] %% Spinal Nucleus Subdivisions subgraph TBNC [Trigeminal Brainstem Nuclear Complex] MN subgraph SN [Spinal nucleus] Oralis[Oralis subnucleus Vo] Interpolaris[Interpolaris subnucleus Vi] Caudalis[Caudalis subnucleus Vc] end end %% Projections to Thalamus TBNC -- "Projection neurones ascend via anterolateral trigeminothalamic tract" --> THALAMUS THALAMUS --> VPM[Ventral posterior medial nucleus] THALAMUS --> PN[Posterior nucleus] %% Thalamus to Cortex THALAMUS --> CORTEX CORTEX --> SS[Somatic sensory cortex] CORTEX --> IC[Insular cortex] CORTEX --> CG[Cingulate gyrus] CORTEX --> FC[Frontal cortex] ```  #### Trigeminal Brainstem Nuclear Complex (TBNC) Structure **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. Labelled diagram of the trigeminal pain pathway. Visualizes sensory inputs from V1 (Skin, Nasal Mucosa, Cranial Vessels, Cornea, Conjunctiva), V2 (Skin, Tooth, Oral Mucosa, Nasal Mucosa), and V3 (Skin, Oral Mucosa, Tooth, Temporomandibular Joint, Cranial Vessels, Jaw muscles) converging at the Trigeminal ganglion. Signals travel via Aδ and C fibers through the Trigeminal spinal tract to the Main nucleus and Spinal nucleus (Oralis subnucleus Vo, Interpolaris subnucleus Vi, Caudalis subnucleus Vc). Projection neurones ascend via the anterolateral trigeminothalamic tract to the Thalamus (Ventral posterior medial nucleus, Posterior nucleus), which projects to the Cortex (Somatic sensory cortex, Insular cortex, Cingulate gyrus, Frontal cortex). Includes a blue star highlighting the 'Spinal nucleus' region. Postsurgical Pain • Nociceptive pain from activation of nociceptors • Inflammatory pain from release of inflammatory mediators • Neuropathic pain from injury of nerves  #### Components of Postsurgical Pain - **Nociceptive pain**: From the activation of nociceptors. - **Inflammatory pain**: From the release of inflammatory mediators. - **Neuropathic pain**: From the injury of nerves. A comprehensive labelled diagram illustrating the pain pathway from injury to cortical perception. It begins with a hand being struck by a hammer (labeled 'Injury'), triggering transduction via nociceptors and inflammatory mediators like bradykinin and serotonin. The signal travels as first-order neurons through the dorsal root ganglion, synapses at second-order neurons in the Rexed laminae of the spinal cord, ascends via spinothalamic tracts to third-order neurons in the ventral posterolateral (VPL) nucleus of the thalamus, and finally projects to the somatic sensory cortex. A separate inset on the right details the Trigeminal Brainstem Nuclear Complex and cranial nerve pathways for head/face sensation, mapping specific areas (V1, V2, V3) to structures like skin, teeth, and mucosa. - Neuropathy is classified into 3 main types: **axonotmesis**, **neurotmesis**, and **neuropraxia**. - Neurotmesis indicates rupture of the nerve trunk where both the axon and axon continuity is completely severed - Axonotmesis indicates the rupture of axons where the surrounding connective tissue of the nerve has been maintained - **Neuropraxia is a transient blockage of nerve conduction without axon alteration.** #### Classification of Nerve Injury (Neuropathy) 1. **Neuropraxia**: A transient blockage of nerve conduction without alteration to the axon. 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. Chronicity of Pain * In general, pain lasting for more than **3** months In orofacial pain: * Pain occurring on >15 days per month and lasting for >2 hours a day for at least 3 months blog #### Defining Chronicity - **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. **Chronicity of Pain** - Neuroplasticity! - Repeated pain exposure changes pain pathways in the brain, making them more sensitive to future pain and increasing the risk of developing chronic pain. - **Peripheral and Central Sensitization** #### Neuroplasticity and Sensitization 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. Sensitization **Published: 15 December 1983** **Evidence for a central component of post-injury pain hypersensitivity** **Clifford J. Woolf** *Nature* 306, 686–688 (1983) | **Cite this article** 3659 Access | 1529 Citations | 84 Altmetric | **Metrics** **Abstract** Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization) or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses. Because sensitization of peripheral receptors occurs following injury, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that **Long-term consequences of noxious stimuli result from central as well as from peripheral changes.** The hallmarks of central sensitization include **decreased threshold firing**, **firing from non-noxious stimuli** and **pain spread**. **Hyperalgesia**: Exaggerated responses to noxious stimuli (hyperalgesia). **Allodynia**: Sensitivity to normally non-noxious mechanical and thermal stimuli #### Mechanisms of Hypersensitivity 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. - **Allodynia**: Pain sensitivity to normally non-noxious mechanical and thermal stimuli. - Repetitive noxious stimulation of primary C-fiber afferents results in a ‘wind-up’ phenomenon - Escalation of nociceptive transmission by cells in the dorsal horn. - Wide-dynamic range neurons recruited resulting in the amplification and prolongation of nociceptive transmission in ascending pathways in the central nervous system. - Central sensitization is mediated via activation of the N-methyl-D-aspartate (NMDA) glutamate receptor and is a feature of many chronic pain states.  #### The 'Wind-Up' Phenomenon - 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. Labelled diagram illustrating the pathway of nociceptive transmission and central sensitization. The visual flow begins with a hand receiving an 'Injury' (hammer icon), leading to chemical mediators (Bradykinin, Serotonin, etc.). This triggers transduction via nociceptive afferents (1st order neurons) to the dorsal root ganglion. Transmission occurs through spinal interneurons (2nd order neurons in Rexed laminae) via the spinothalamic tract to the ventral posterolateral (VPL) nucleus of the thalamus (3rd order neurons). Finally, the signal projects to the ipsilateral postcentral gyrus (primary somatosensory cortex). The diagram visually connects these anatomical structures with arrows to demonstrate the escalation of pain signals. # Neuropathic Pain Prevalence ## **Prevalence of neuropathic pain in the general community > 2%** ## **One-third of cancer patients have neuropathic pain (alone or with nociceptive pain)** ## **>50% of low back pain patients have associated neuropathic pain** **SPHERE Positive Management of Persistent Pain Algorithms (2006). Schmader KE. Clin J Pain 2002; 18: 350-4. Stevens PE, et al. Pain 1995; 61: 61-8. Davis MP, Walsh D. Am J Hosp Palliat Care 2004; 21: 137-42. Deyo RA, Weinstein JN. NEJM 2001; 344: 363-70** #### General Prevalence Data - **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. * Incidence following injury to the peripheral branches of the trigeminal nerve following implants, 3rd molar extractions, orthognathic surgery, mid face fractures and root canal therapy: **3-5%** IASP 2016 #### Trigeminal Nerve Injury Incidence 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). Third Molar Surgery Renton T, Yilmaz Z. Profiling of patients presenting with posttraumatic neuropathy of the trigeminal nerve. J Orofac Pain. 2011 Fall;25(4):333-44. PMID: 22247929.  #### Posttraumatic Neuropathy Research regarding the profiling of patients presenting with posttraumatic neuropathy of the trigeminal nerve, specifically following third molar surgery (Renton & Yilmaz, 2011). Clustered bar chart titled 'Third Molar Surgery' (indicated by handwritten annotation). The Y-axis represents the 'Percentage of patients' ranging from 0 to 80. The X-axis lists various dental procedures: IMS, LA, Implants, Endodontics, Apicectomy, Pathological excision, Apical infections, Assault, and Drill. A legend in the top right distinguishes between two categories: 'IANI' (blue bars) and 'LNI' (red/maroon bars). Notable data points show that IANI is approximately 60% for IMS, while LNI is over 70%. Other procedures like LA and Implants show lower percentages. # Who can Get Chronic Pain? ## Anyone  #### Risk Groups Chronic pain can affect anyone. Illustration of a cartoon character resembling Homer Simpson with an exaggerated expression. The image includes the text 'NO BRAIN' curved above the head and 'NO PAIN' curved below the chin, visually reinforcing the concept that pain is linked to brain function. **Biopsychosocial Model** **Bio** Partial genetic susceptibility Biological pain processes **Psycho** **Psychological** Perpetuating Factors **Social** Life stressors Work Claim Access to care Sleep, alcohol, other pain conditions, smoking  #### Components of the Biopsychosocial Model - **Biological (Bio)**: Partial genetic susceptibility and biological pain processes. - **Psychological (Psycho)**: Perpetuating psychological factors. - **Social**: Life stressors, work claims, access to care, sleep quality, alcohol use, smoking, and other comorbid pain conditions. Labelled diagram titled 'Biopsychosocial Model' illustrating the intersection of three domains. The visual consists of three overlapping circles: a green circle labeled 'Bio', an orange circle labeled 'Psycho', and a yellow circle labeled 'Social'. Associated labels are positioned around the shapes: 'Partial genetic susceptibility' and 'Biological pain processes' point to the Bio section; 'Psychological Perpetuating Factors' points to the Psycho section; and 'Life stressors, Work Claim, Access to care, Sleep, alcohol, other pain conditions, smoking' points to the Social section. Axis I Somatosensory Input Axis II Psychosocial Input ## Suffering and **Pain Behavior** Acute pain Chronic pain Time Time [this chart helps to predict pain](#) [learning the risk factars](#) [code for vectors: ll \lambda_2, \psi,]   #### Dual Axis Assessment - **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. A conceptual diagram illustrating the transition from Acute pain to Chronic pain. The diagram features a timeline axis labeled 'Time' at the bottom. It depicts two input axes: 'Axis I Somatosensory Input' (yellow region) and 'Axis II Psychosocial Input' (blue region). On the left, under 'Acute pain', the diagram shows a large yellow area with a small blue section, indicating dominance of somatosensory input. An arrow points from this configuration to 'Suffering and Pain Behavior'. On the right, under 'Chronic pain', the blue 'Psychosocial Input' area significantly expands while the yellow area shrinks. Arrows point down from both axes into smaller blocks below, representing the inputs during chronic pain. A photograph showing a woman dressed in ornate gold jewelry and headwear against a dark blue background. She is holding a glowing crystal ball between her hands, symbolizing prediction or looking into the future. This image serves as a visual metaphor for the caption text which mentions that the chart helps to 'predict pain'. # Pain Vulnerability Predictors * Female * Comorbid chronic pain conditions * Stress * Anxiety * Neuroticism * Catastrophizing | Chronic Fatigue Syndrome | Interstitial Cystitis | Vulvodynia | | Chronic Migraine | Irritable Bowel Syndrome | Endometriosis | | Chronic Tension-Type Headache | | Temporomandibular Disorders | | | Chronic Low Back Pain | | **Findings.** A sample of chronic overlapping pain conditions (Courtesy CRPA). PracticalPainManagement.com  #### Risk Factors for Pain Vulnerability - Female gender - Stress and Anxiety - Neuroticism - Catastrophizing - Presence of comorbid chronic pain conditions #### Chronic Overlapping Pain Conditions - Chronic Fatigue Syndrome - Chronic Migraine - Chronic Tension-Type Headache - Interstitial Cystitis - Irritable Bowel Syndrome - Chronic Low Back Pain - Vulvodynia - Endometriosis - Temporomandibular Disorders (TMD) A Venn diagram illustrating a sample of chronic overlapping pain conditions. It consists of multiple colored circles (purple, teal, pink) intersecting to show comorbidities between specific conditions. Labeled regions include: 'Chronic Fatigue Syndrome', 'Interstitial Cystitis', 'Vulvodynia', 'Fibromyalgia', 'Irritable Bowel Syndrome', 'Endometriosis', 'Chronic Migraine', 'Temporomandibular Disorders', 'Chronic Tension-Type Headache', and 'Chronic Low Back Pain'. The caption below reads: 'Figure 1. A sample of chronic overlapping pain conditions (Courtesy CRPA).' Source: PracticalPainManagement.com. # Mismanagement of dentoalveolar pain What are the clinical consequences? Charles S. Greene, DDS, Dr Ortho • Daniele Manfredini, DDS, PhD   #### Clinical Consequences of Dentoalveolar Pain Mismanagement What are the clinical consequences of the mismanagement of dentoalveolar pain? Clinical photo: A middle-aged woman wearing a striped tank top is holding a small pink box with white polka dots containing facial wipes. She is reaching up to pull a tissue from the box, illustrating the inciting incident described in the text where the box slipped and struck her upper lip. Figure: A green header block displaying the title of the article 'Mismanagement of dentoalveolar pain' along with author names Charles S. Greene and Daniele Manfredini, publication details for JADA (Journal of the American Dental Association), and the DOI link. Online she found a **prosthodontist** (dentist no. 3) who had been a part-time faculty member at a local dental college. He examined her approximately 2 months after the **RCT** was performed. He examined her by tapping on tooth 21 with a blunt instrument and found her responses to be indicative of a DAP problem, so he referred her to a **periodontist** (dentist no. 4). This led to the following series of evaluations and treatments by these 2 dentists and 3 other colleagues within 2 dental group practice offices. First, dentist no. 4 concluded that tooth 21 was cracked, and he extracted it; an immediate implant was placed during that visit. Afterward, a temporary crown was placed by dentist no. 3. Because the pain persisted, the patient was seen by an **endodontist** (dentist no. 5) within that same group practice, and he performed RCT on tooth 22. The same cycle of events as described for 21 was repeated as the pain was getting worse, and extraction was recommended. Also, owing to a questionable radiographic finding around the tip of implant for tooth 21, that implant was removed during the same visit. At this point, the patient went to a different dental office to see another periodontist (dentist no. 6), who asked the endodontist in his practice (dentist no. 7) to evaluate the completed RCT on tooth 22. Together they decided to extract this tooth on the basis of **a cracked root**. An implant was placed, and it has not been removed to date. Throughout all of this treatment, provided over a **3-year span**, the patient’s symptoms steadily worsened. During this entire 3-year period, not 1 of the 7 dentists ever mentioned an alternative diagnosis other than toothache or cracked root, nor was it ever suggested that the patient should consult with an OFP or oral medicine specialist or with a physician of any kind. Finally, the patient sought an opinion at the Mayo Clinic, where within 30 minutes a diagnosis of atypical odontalgia was offered; this diagnosis has changed nomenclature over the succeeding years, but essentially it was a correct description of a neuropathic pain problem. A first attempt to treat with **gabapentin** did not help. The patient returned home and began a cross-country odyssey seeking treatment. One **neurologist** in New York suggested a microvascular decompression surgical procedure to treat what he diagnosed as trigeminal neuralgia, but another neurologist warned her against it. She saw **oral surgeons** in a Midwestern state who advertise treatment for neuralgia-inducing cavitational osteonecrosis (NICO) (also described as holes in bone), for which they recommended performing a surgical excavation procedure of the dentoalveolar bone. At this time, the patient was referred to the article’s first author (C.S.G.) and was advised to avoid that NICO procedure. An oral stent containing a custom-compounded mixture of various medications for neuropathic pain (that is, pregabalin, cortisone, and lidocaine) was fabricated; this was inserted over the painful area, and that was moderately helpful for some time, but ultimately it did not provide adequate relief. The patient then was referred for neurologic care, and a series of medications for neuropathic pain was tried with limited success. Somehow, she has managed to continue working as a teacher most of this time. Ultimately, after failing to improve with stellate ganglion blocks for a supposed sympathetically maintained pain disorder, she was prescribed opioid medications to be taken 4 times per day combined with other centrally acting medications. The patient understandably was distressed and consulted with an attorney. She wanted to sue all 7 dentists but ultimately was persuaded that dentist no. 1 had done the best he could with vague symptoms and no findings and that his 6-month collaboration with the endodontist (dentist no. 2) was acceptable. Performing the RCT on 21 also seemed reasonable at the time, but it is unfortunate that the endodontist did not understand the negative outcome; instead, he attempted prescribing medications and hoping for resolution of the pain. Clearly, it is fair to think that dentist no. 3 erred by failing to consider a nonodontogenic diagnosis when this new patient with 1 year of progressively increasing DAP sought treatment at his office. Instead, he initiated the cycle described above, and the following 6 years of pain could be attributed to the combination of omissions (failure to diagnose or refer) and commissions (extractions, implant placement and removal, etc.) committed by him and his 4 colleagues. Therefore, a **malpractice suit** was brought against all 5 of those dentists; the outcome of that action is still pending. #### Progression of Invasive Dental Interventions 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 woman - Wanted to 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. - Nonacceptance of working diagnosis of neuropathic pain #### Case 2: 27-Year-Old Woman - 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. She recalled her initial problem as pain in the maxillary right arch, in the area of premolars, approximately 5 years earlier. Her general dentist attributed the pain to pulpal inflammation of the first premolar and performed an endodontic treatment. After an initial improvement, the pain soon reappeared, and the dentist attributed the pain to sensitivity of the neighbouring teeth. He proceeded with additional sequential RCTs of teeth to provide possible relief from pain, which was migrating from 1 tooth to another. How many? #### Clinical History 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 neighboring teeth and proceeded with additional sequential root canal treatments (RCTs) as the pain migrated from one tooth to another. How many? 28 Persistent Idiopathic Dentoalveolar Pain Persistent Idiopathic Dentoalveolar Pain  Clinical panoramic radiograph (OPG) of the mandible and maxilla showing dental arches with multiple teeth. The image includes anatomical structures such as the mandibular ramus, condyles, and maxillary sinuses. A small 'L' marker is visible in the bottom right corner indicating left side orientation.   Clinical photograph of the patient in case report 2 showing a close-up view of the upper and lower anterior teeth. The image displays full crowns on all visible teeth, with healthy-looking gingiva. A dental retractor is used to hold the lips back. Clinical photograph of the patient in case report 2 (left-side view). This image shows the patient's dentition from a different angle compared to the first photo, also displaying full crowns on all teeth held open by a retractor. * After these extensive procedures, her overall **<mark>pain increased</mark>**, with alternating periods of slight remissions and worsening episodes. The patient described the pain as feeling like an **<mark>electrical stimulus</mark>** 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 **<mark>burning sensation in the gingiva</mark>** as well as a **<mark>bad taste</mark>** in the mouth. She reported **<mark>headaches</mark>** with a frequency of no less than 7 days per month. Prosthetic treatment was proposed to underline *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.* #### Clinical Progression and Symptoms 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 terminology** * Anaesthesia dolorosa, painful post-traumatic trigeminal neuropathy, persistent dentoalveolar pain, deafferentation pain, phantom tooth pain, atypical odontalgia, atypical facial pain. * 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. * Post-traumatic trigeminal neuropathic pain rarely, if ever, crosses the midline but, over time, it may in some cases become more diffusely distributed.  #### Previous Terminology - 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. Post-traumatic trigeminal neuropathic pain rarely, if ever, crosses the midline but, over time, it may in some cases become more diffusely distributed. Hand-drawn schematic diagram illustrating the relationship between 'Previous terminology' and a list of medical conditions. A red curly brace on the left connects to a handwritten label 'Previous terminology', which points via an arrow to a bulleted list containing: Anaesthesia dolorosa, painful post-traumatic trigeminal neuropathy, persistent dentoalveolar pain, deafferentation pain, phantom tooth pain, atypical odontalgia, atypical facial pain. ## Epidemiology * Rare * Good estimates of the prevalence of PTTN lacking * ? Shifting diagnostic terms and criteria * Traumatic injuries to the trigeminal nerve only rarely lead to a painful neuropathy * Onset usually in middle age (40-50 years) * More common in females * Associated with significant psychosocial stressors #### Epidemiological Factors - 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 # Clinical Presentation - Oral or facial pain developing within 6 months - Identifiable traumatic event to the trigeminal nerve - The pain persists beyond the normal healing time - Usually unilateral - Pain is localised to the distribution of the trigeminal nerve - Symptoms vary considerably. - Quality: Often burning or shooting - Swollen or foreign body sensation, heat or cold, or redness/flushing. - Moderate to severe intensity. - Duration: Often continuous, but may be paroxysmal or mixed. - There may be clinical signs of hyperalgesia/allodynia or hypoaesthesia/hypoalgesia. #### Diagnostic Criteria - 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 # Management * 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 op adequate anesthesia) * Pharmacologic: * Topical – e.g. local anaesthetics, capsaicin * Systemic – e.g. tricyclic antidepressants, gabapentinoids, anticonvulsants, selective noradrenaline reuptake inhibitors * Psychological, cognitive behavioural approaches #### General Principles - 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 <table> <tr> <td>Drug</td> <td>Mechanism of action</td> <td>Active ingredient<sup>a</sup></td> <td>Daily dose</td> </tr> <tr> <td>Tricyclic antidepressants (TCAs)<sup>1,2</sup></td> <td>Inhibit the reabsorption (reuptake) of serotonin and norepinephrine</td> <td>Amitriptyline</td> <td>10-200 mg</td> </tr> <tr> <td>Phenothiazines<sup>18</sup></td> <td>Block dopamine D2 receptor</td> <td>Chlorpromazine</td> <td>60-300 mg</td> </tr> <tr> <td>Beta-blockers<sup>19</sup></td> <td>Beta-blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline</td> <td>Propranolol</td> <td>5-50 mg</td> </tr> <tr> <td>Anticonvulsants<sup>20-25</sup></td> <td>Intervene on the canal<sup>b</sup> Ca<sup>2+</sup></td> <td>Gabapentin</td> <td>300-3600 mg</td> </tr> <tr> <td></td> <td></td> <td>Pregabalin</td> <td>300-600 mg</td> </tr> <tr> <td></td> <td></td> <td>Clonazepam</td> <td>1-10 mg</td> </tr> <tr> <td>Agonist of GABA receptor<sup>19</sup></td> <td>Acts on the CNS to produce its muscle relaxant effects</td> <td>Baclofen</td> <td>30-200 mg</td> </tr> <tr> <td>Topical medications<sup>1</sup></td> <td>Capsaicin encourages the release of substance P, inhibiting its biosynthesis and axonal transport, leading to a depletion of substance P in the central and peripheral nervous systems.</td> <td>Capsaicin</td> <td>0.025% topical</td> </tr> <tr> <td>Minor opiate analgesics<sup>26</sup></td> <td>Minor opiate analgesics act to relieve pain in the CNS</td> <td>Tramadol Codeine</td> <td>100-400 mg</td> </tr> </table>  #### Pharmacological Management Table | 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 | A table titled 'Table II. Most common drugs in neuropathic pain' from a medical document (Rodríguez-Lozano et al., April 2010). The table is organized into four columns: 'Drug', 'Mechanism of action', 'Active ingredient', and 'Daily dose'. It lists various drug classes including Tricyclic antidepressants (TCAs), Phenothiazines, Beta-blockers, Anticonvulsants, Agonist of GABA receptor, Topical medications, and Minor opiate analgesics. Specific examples like Amitriptyline, Gabapentin, Pregabalin, Baclofen, Capsaicin, Tramadol, and Codeine are listed with their corresponding mechanisms and dosages. Renton, Dawood, Shah, Searson & Yilmaz, 2012   Renton, Dawood, Shah, Searson & Yilmaz, 2012 Table titled 'Reported incidence and risk factors for implant related inferior alveolar nerve injury'. Contains columns for Study author/year, Descriptive details of cases (e.g., chronic pain resolved after implant removal, neuropathic implications), and Incidence of nerve injury percentages. Lists multiple studies including Balshi (1989), Delcanho (1995), Rubenstein and Taylor (1997), Wismeijer et al. (1997), Bartling et al. (1999), Walton (2000), Von Arx et al. (2005), and Hillerup (2007). Table titled 'Summary of data on referral delay, radiographic proximity to the inferior alveolar nerve (IAN) canal, and mechanosensory function'. Divided into three sections: Referral Delay (listing frequencies for timeframes like Within 24 hours, Within 48 hours, etc.), Radiographic proximity (listing preparation breach, implant breach, crossing IAN canal, etc.), and Mechanosensory function (listing categories from Increased to None with corresponding frequencies). Summary points from paper • Patients were aware of signing consent forms for the surgery in 11 cases and 8 of those felt they were not explicitly warned about nerve injury. • Over 70% of patients were referred after six months post injury. • CBCT (10%), dental pantomograph (50%) and long cone periapical radiographs (48%). However, no radiographic evidence 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. #### Summary Points from Research - 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 - **Other names**: atypical facial pain, phantom toothache - **AO as a subform of PIFP?** - **Persistent oral and/or facial pain** with varying presentations, **in the absence of clinical neurological deficit** - **Characterised by daily (or near daily) pain that may spread to different locations** - **May be part of a continuum with PPTTN** #### Overview and Terminology - **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 • Rare • Onset usually in middle age • Female predominance • Associated with central sensitivity syndrome, with comorbidities such as chronic widespread pain, fibromyalgia, and irritable bowel syndrome • Associated with high levels of psychiatric comorbidity and psychosocial disability. #### Epidemiology and Comorbidities - **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. # Clinical Presentation * Oral and/or facial pain that is **poorly localised**, and does not follow the distribution of a peripheral nerve. Pain persists beyond the normal healing time. * The pain is initially confined, but may subsequently spread in a non-dermatomal pattern. * Onset of symptoms may not necessarily be associated with a physically traumatic event. * Clinical neurological examination is normal. #### Localization and Onset - **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. - Symptoms vary considerably. - Quality: often dull, aching or nagging, sometimes with sharp exacerbations, but other pain qualities may also be described. - Mild to severe intensity. - Duration: often continuous, and recurs daily. - Aggravated by stress. - Often co-existing chronic orofacial pain or headache. - No dental cause identified. #### Symptom Characteristics - **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 ~~NOT ON EXAM~~ - **Facial and/or oral pain fulfilling criteria B and C - Recurring daily for >2 hours/day for >3 months** - **Pain has both of the following characteristics:** - poorly localized, and not following the distribution of a peripheral nerve - dull, aching or nagging quality - **Clinical neurological examination is normal** - **A dental cause has been excluded by appropriate investigations** - **Not better accounted for by another ICHD-3 diagnosis** #### ICHD-3 Diagnostic Criteria 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. 6. **Differential Diagnosis**: Not better accounted for by another ICHD-3 diagnosis. # Management ## Difficult to manage. ## Usually requires management by pain specialists in a multidisciplinary setting ## May involve pharmacological therapy (e.g. tricyclic antidepressants, gabanoids, anticonvulsants, selective noradrenaline reuptake inhibitors), cognitive behavioural therapy and psychotherapy. #### Management Strategies - **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 *Exam** • 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. • Middle to old age. • More common in females. **Is this a trigeminal neuropathy?** #### Definition and Overview - **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 - Classical Trigeminal Neuralgia – neurovascular conflict at the trigeminal nerve root entry zone - Secondary Trigeminal Neuralgia – space-occupying lesion, multiple sclerosis or other abnormality - Idiopathic Trigeminal Neuralgia – no obvious cause - Trigeminal nerve root atrophy (demyelination) and/or displacement leading to ectopic firing of neurons. #### Classification of Trigeminal Neuralgia - **Classical Trigeminal Neuralgia:** Neurovascular conflict at the trigeminal nerve root entry zone. - **Secondary Trigeminal Neuralgia:** Space-occupying lesion, multiple sclerosis, or other abnormality. - **Idiopathic Trigeminal Neuralgia:** No obvious cause. #### Pathophysiology - Trigeminal nerve root atrophy (demyelination) and/or displacement leading to ectopic firing of neurons. Larger font size **Clinical Presentation** - Recurrent severe paroxysmal pain in one or more divisions of the trigeminal nerve - Usually unilateral - Quality: Electric shock, shooting, stabbing, sharp - Usually lasts a fraction of a second - Triggered by innocuous stimuli (e.g. light touch, talking, chewing) - Can present with concomitant background pain between the attacks Other cranial neuralgias - These clinical features can also occur in the distribution of other sensory nerves (e.g. glossopharyngeal neuralgia, occipital neuralgia) #### Clinical Presentation - 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. #### Related Conditions - These clinical features can also occur in the distribution of other sensory nerves (e.g., glossopharyngeal neuralgia, occipital neuralgia). # Diagnosis ## <div>Digital or traditional pathology slides</div>: - Clinical diagnosis - Investigations – <span style="background-color: yellow;">MRI</span> to assess for cause - Atypical presentations (e.g. bilateral pain in a younger patient, involvement of multiple cranial nerves, coexisting sensory or motor disturbances) may suggest other pathology and requires specialist assessment  #### Diagnostic Process - 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. Medical imaging photo showing two axial MRI scans of a brain displayed on a monitor. The image includes technical scan parameters overlaid in text (e.g., TR, TE, FoV). This visual supports the OCR context regarding 'Investigations – MRI to assess for cause' and serves as an example of diagnostic imaging. # Management * Pharmacologic * First line therapy is carbamazepine * Severe adverse effects! * E.g. Stevens-Johnson Syndrome and bone marrow depression * Other medications * anticonvulsants, gabapentinoids and baclofen * Neurosurgery * Microvascular decompression, rhizotomy, balloon compression, gamma knife #### Pharmacologic Management - **First-line therapy:** Carbamazepine. - **Adverse effects:** Risk of severe reactions, such as Stevens-Johnson Syndrome and bone marrow depression. - **Other medications:** Anticonvulsants, gabapentinoids, and baclofen. #### Neurosurgical Interventions - Microvascular decompression. - Rhizotomy. - Balloon compression. - Gamma knife. # Trigeminal Post-Herpetic Neuralgia * Other names: Post-herpetic trigeminal neuropathy * Unilateral neuropathic facial pain in the distribution of the trigeminal nerve caused by herpes zoster * Can persist for months to years. * 25-50% of patients >50 years with herpes zoster develop PHN (≥3 months after healing of rash) #### Overview and Definition - **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. # Epidemiology **Risk factors for developing post-herpetic neuralgia include:** * **Over 60 years of age.** * **Severe herpes zoster rash.** * **Severe pain during herpes zoster.** * **Immunocompromised individuals.** * **Ophthalmic involvement.**  #### Risk Factors 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. Vertical stack of colored rectangular boxes illustrating risk factors for post-herpetic neuralgia. The top blue box serves as a header titled 'Risk factors for developing post-herpetic neuralgia include:'. Below are five sequential green and teal boxes listing specific factors: 'Over 60 years of age.', 'Severe herpes zoster rash.', 'Severe pain during herpes zoster.', 'Immunocompromised individuals.', and 'Ophthalmic involvement.'. | Clinical Presentation | |---| | **Unilateral facial pain in the same trigeminal nerve branch(es) as the herpes zoster infection** | **Quality: Burning, itching** | **Moderate intensity** | | Pain may be continuous, or sometimes display intermittent shooting/electric shock-like attacks | Allodynia and hyperalgesia | Most commonly affects the ophthalmic division of the trigeminal nerve. |  #### Clinical Presentation - **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. A structured table summarizing the clinical presentation of trigeminal neuralgia or post-herpetic neuralgia. The layout consists of six colored rectangular panels arranged in two rows and three columns. Top row (left to right): Orange panel with text 'Unilateral facial pain in the same trigeminal nerve branch(es) as the herpes zoster infection'; Grey panel with 'Quality: Burning, itching'; Yellow panel with 'Moderate intensity'. Bottom row (left to right): Blue panel with 'Pain may be continuous, or sometimes display intermittent shooting/electric shock-like attacks'; Green panel with 'Allodynia and hyperalgesia'; Orange panel with 'Most commonly affects the ophthalmic division of the trigeminal nerve.'. # Management * Difficult to manage * The risk of developing post-herpetic neuralgia may be reduced by **treating herpes zoster early**, and vaccination of adults over 50 years of age to **minimise varicella zoster virus reactivation**. * Topical therapy – e.g. **capsaicin (watch the eyes!)**, lidocaine * Systemic therapy – e.g. **gabanoids**, tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors #### Management and Prevention 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). - Lidocaine. - **Systemic Therapy:** - Gabapentinoids. - Tricyclic antidepressants. - Serotonin-noradrenaline reuptake inhibitors (SNRIs). # Oral Burning Oral Burning “Jane” • 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. • Hx Type 2 diabetes, asthma, gastroesophageal reflux, hypertension, depression and anxiety. • Her daily medications include metformin, warfarin, escitalopram, pantoprazole, ramipril, fluticasone puffer • Never smoker, 1–2 standard alcoholic beverages per week. #### Case Study: "Jane" - 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. What are the possible causes of oral burning? **What are the possible causes of oral burning?** Most common? Is it Burning Mouth Syndrome? Is BMS the best name for it? * Nomenclature * **Subjective** xerostomia, **dys**aesthesia and **dys**geusia (altered taste) are present in two-thirds of cases reported. #### Clinical Considerations - 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. **POSSIBLE CAUSES OF ORAL BURNING** A SPOONFUL OF ORAL MEDICINE --- <table> <tr><th>Cause Category</th></tr> <tr><td>Oral Burning<br>Oral Medicine / Oral Pathology</td></tr> <tr><td>Idiopathic<br><b>E.g. Burning Mouth Syndrome</b><br>Oral Dysaesthesia</td></tr> <tr><td>Infective<br><b>E.g. Candidosis, Viral</b></td></tr> <tr><td>Degenerative<br><b>E.g. Alzheimer's</b></td></tr> <tr><td>Systemic<br><b>E.g. Nutritional Deficiencies, Hematinic Deficiencies, Hormonal Changes, Age Related Changes, Renal Problems, Psychiatric Issues</b></td></tr> <tr><td>Metabolic<br><b>E.g. Diabetes, Thyroid Dysfunction</b></td></tr> <tr><td>Iatrogenic<br><b>E.g. Medication Related</b></td></tr> <tr><td>Traumatic (Iatrogenic)<br><b>E.g. Radiotherapy, Surgery</b></td></tr> <tr><td>Neoplastic<br><b>E.g. CNS Pathology</b></td></tr> <tr><td>Autoimmune<br><b>E.g. Sjogrens</b></td></tr> <tr><td>Immune-Mediated<br><b>E.g. Oral Mucosal Diseases such as Oral Lichen Planus</b></td></tr> <tr><td>Traumatic<br><b>E.g. Damage from causes such as GORD/Anorexia, Dehydration</b></td></tr> </table> Most common cause **Thank you for reading!** **Dr Amanda Phoeon Nguyen**  #### Etiology of Oral Burning - **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 A mind map diagram illustrating the 'Possible Causes of Oral Burning'. The central yellow node is labeled 'ORAL BURNING' with an Instagram handle below. Connected to the center by white lines are ten surrounding nodes representing different cause categories: Infective (e.g., Candidosis), Idiopathic (e.g., Burning Mouth Syndrome), Neoplastic (CNS Pathology), Immune-Mediated (Oral Lichen Planus), Autoimmune (Sjogrens), Traumatic (GORD/Anorexia), Traumatic (Iatrogenic) (Radiotherapy/Surgery), Iatrogenic (Medication Related), Metabolic (Diabetes/Thyroid), and Systemic (Nutritional/Hormonal changes). A handwritten arrow points from the 'Iatrogenic' node to a caption reading 'Most common cause'. An inset photo on the left depicts a smiling mouth with a fire icon over the teeth. 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)  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) Clinical photograph showing a set of dentures (upper and lower) alongside two partial dentures with metal clasps. The image is placed on the right side of the slide next to the text listing 'Possible causes of oral burning include: ... traumatic, including iatrogenic causes (e.g radiotherapy to the oral cavity), or physical, thermal or chemical trauma'. The visual context suggests these dental prosthetics are relevant examples of potential traumatic or physical causes of oral burning. - Thorough! - Consider by a range of systemic and local factors - Some considerations include: - Jane’s medications, diabetic control, asthma and hypertensive control - nutritional deficiencies and diet  #### Diagnostic Considerations - 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. Illustration of a medical clipboard with checkmarks and icons representing health monitoring (plus sign, person icon). Contextually linked to the text 'Medical History' and considerations such as medications, diabetic control, asthma, hypertensive control, and nutritional deficiencies. ### History taking It is important to seek a history of the oral burning, including: - Symptoms - Date of onset - Precipitating event - Previous treatments trialled - other investigations undertaken - Quality of the pain - Intensity of the symptoms - Exacerbating or relieving factors. #### History Taking Elements 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 # Medications * Medication-related adverse effect * Extensive list * Examples include: antihypertensives, antibiotics, neurological medications, cardiac medications, endocrine medications and psychotropic medications * Most commonly implicated: ACE inhibitors and angiotensin receptor blockers #### Medication-Related Adverse Effects 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. Supplements **Vitamin B₆ /pyridoxine** Doses ≥200 mg/day of vitamin B₆ have been associated with severe sensory peripheral neuropathies. Risk often arises from multiple products being taken all containing pyridoxine. **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. AM GM. The safety of commonly used vitamins and minerals. Aust Prescr 2021;44:119- 23. https://doi.org/10.18773/austprescr.2021.029 <img>Signpost labeled "Vitamin"<img>  #### Supplement-Related Effects - **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. Photo of a road sign with an arrow pointing left and the word 'Vitamin' on it, set against a blue sky.   Product photo of 'Nature's Essence' Andrographis Antiphlogistic Tablets. The image shows the green cardboard box and a white plastic bottle with matching labels. Key text includes product name in English ('ANDROGRAPHIS ANTIPHLOGISTIC TABLETS') and Chinese ('穿心莲'), indications for use such as sore throat and fever, quantity (100 tablets), and origin ('MADE IN SINGAPORE'). Close-up product photo of 'BioCeuticals ArmaForce' supplement bottle. The label features a blue and gold design. Text identifies it as 'Standardized Andrographis and Olive Leaf with Echinacea'. Visible details include the brand logo, product name, serving size information, and an expiration date stamp. # Psychosocial history • Psychological and psychiatric comorbidities are more prevalent in patients experiencing oral burning. • Some patients with oral burning have a high incidence of anxiety, depression and personality disorders. #### Psychosocial History - 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.** No supplements, no diet changes. # Dental History and Examination - Associated symptoms? - Xerostomia, salivary gland hypofunction, dysaesthesia and dysgeusia - A history of trauma - Chemical, mechanical or thermal trauma - Parafunctional habits- tongue thrusting - Mucosal lesions/diseases such as oral infections (e.g oral candidosis), mucocutaneous lesions (e.g oral lichen planus) and other mucosal reactions such as hypersensitivity, contact allergy and lichenoid reactions can be associated with oral burning #### Dental History and Examination - **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 </img> • Jane is partially edentulous and wears a full upper denture. She rarely removes it at night. Her upper denture is more than 10 years old and poorly fitting • She also does not rinse out her mouth after steroid puffer use • Clinically, you see creamy, semi-adherent plaques in the maxillary buccal sulcus • The rest of her E/O and I/O examination is unremarkable • Her CN exam reveal no remarkable findings #### Clinical Findings for Jane - **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. <img>Creamy, semi-adherent plaques in the maxillary buccal sulcus (Oral Candidiasis).<img> Based on her history and exam, what would be the most likely diagnosis?  Creamy, semi-adherent plaques in the maxillary buccal sulcus (Oral Candidiasis). Based on her history and exam, what would be the most likely diagnosis? Clinical photo showing creamy, semi-adherent white plaques on the mucosa of the maxillary buccal sulcus. The caption identifies this as 'Figure 1' demonstrating Oral Candidiasis. Proposed Paper: Investigating the causes and treatment of "oral burning". Dr R. O'Roarke & M. Tsamb **What further tools or investigations would be helpful in establishing the cause of her oral burning?** What further tools or investigations would be helpful in establishing the cause of her oral burning? # Further investigations - **Serology and saliva testing (with limitations).** - **Is there objective salivary gland hypofunction?** ## **Consider:** - **nutritional abnormalities (e.g vitamin B12, folic acid or iron deficiencies)** - **Diabetes mellitus** - **Hormonal deficiencies** #### Further Investigations - Serology and saliva testing (with limitations). - Assessment for objective salivary gland hypofunction. **Consider testing for:** - Nutritional abnormalities (e.g., vitamin B12, folic acid, or iron deficiencies) - Diabetes mellitus - Hormonal deficiencies A list of medical investigation steps and considerations for diagnosing salivary gland issues. The text includes: 'Serology and saliva testing (with limitations)', 'Is there objective salivary gland hypofunction?', followed by a 'Consider:' section listing 'nutritional abnormalities (e.g vitamin B12, folic acid or iron deficiencies)', 'Diabetes mellitus', and 'Hormonal deficiencies'. ### Blood Tests "Send to GP for blood tests" FBC, iron studies, serum folate and vitamin B12 levels * Vitamins B1, B2 and B6 and zinc, although a strong association has not been shown. * *Serum zinc: not always useful * Thyroid function test (if patient has other symptoms that support this suspicion. * HbA1c Other serology: Autoimmune investigations * Sjogren’s syndrome and systemic lupus erythematosus #### Blood Tests - **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. • Based on Jane’s history, I order a FBC, iron studies and tests for vitamin B12, serum folate and glycated haemoglobin. All serological tests are 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? #### Case Progress - 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 * **BMS** * oral dysaesthesia or complex oral sensitivity disorder. Older terminology includes ‘stomatodynia’, ‘glossopyrosis’ or ‘glossodynia’. * Other “classifications”: Types 1,2,3. primary and secondary * It is a <u>diagnosis of exclusion</u> * Not actually a syndrome * BMS is defined as ‘a chronic intraoral burning sensation that has no identifiable cause – either local or systemic condition * “Normal” clinical signs and laboratory findings * Intensity can fluctuate #### Definition and Terminology - **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 * Affects between 0.1% and 3.9% of the general population * Can be seen in anyone, more commonly in postmenopausal women. * The cause of BMS is poorly understood, but hypotheses include peripheral neuropathy or neuropathic pain, with central sensitisation. * Varying levels of changes in somatosensory function in patients with this condition. #### Epidemiology and Pathophysiology - **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 definition ## 6.1 Burning mouth syndrome (BMS) 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. **Diagnostic criteria:** **A.** Oral pain fulfilling criteria B and C **B.** Recurring daily for <b>>2 hours per day for >3 months</b> *if less than, probable BMS **C.** Pain has both of the following characteristics: - burning quality - felt superficially in the oral mucosa **D.** Oral mucosa is of normal appearance, and local or systemic causes have been excluded **E.** Not better accounted for by another ICOP or ICHD-3 diagnosis. - 6.1 implies that quantitative sensory testing has not been performed. #### ICOP Diagnostic Criteria (6.1) 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? How is burning mouth syndrome (BMS) treated? # Management - Need to be conscious of expectations and effect on quality of life. - Chronic - Management may be difficult - Needs consideration of any perpetuating psychosocial factors. - Typically referred to oral medicine specialist or other appropriate specialist - Multidisciplinary management considered e.g psychological support #### Management Principles - **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). Pharmacotherapy Many pharmacological treatments have been trialled, including topical or systemic **clonazepam**, gabapentinoids, tricyclic antidepressants and antispasmodics. - Success rates vary considerably. #### Pharmacotherapy Various pharmacological treatments have been trialled with varying success rates: - Topical or systemic clonazepam - Gabapentinoids - Tricyclic antidepressants - Antispasmodics Other - Vitamin B12 or zinc supplementation - Alpha-lipoic acid - Palmitoylethanolamide - Low-level laser therapy - Capsaicin mouthwashes To date, few effective treatments are available, and management of BMS can be challenging. My stash! ARE YOU A SPICE LOVER LIKE I AM? Ever wondered how capsaicin reduces oral burning? Studies have shown that there is up-regulation of TRPV1-positive nerve fibres in tongue mucosa in patients with Burning Mouth Syndrome (also known as oral dysesthesia). The vanilloid receptor-1 (TRPV1) is a voltage-dependent cation channel expressed by the unmyelinated C-nociceptive nerve fibres. The receptor may be activated by capsaicin (from chili peppers), heat and H+ (see image below). Capsaicin binds to the TRPV1 receptor causing depolarization of the C-nociceptors. Prolonged activation of these neurons by capsaicin depletes pre-synaptic substance P and makes them less likely to report pain.   #### Other Treatment Modalities - Vitamin B12 or zinc supplementation - Alpha-lipoic acid - Palmitoylethanolamide - Low-level laser therapy - Capsaicin mouthwashes Management remains challenging as few highly effective treatments are available. Scientific diagram illustrating the mechanism of TRPV1 receptor activation. The visual depicts a cell membrane structure with a central orange oval labeled 'TRPV1' acting as a voltage-dependent cation channel. A blue arrow points downwards into the channel, representing the influx of ions labeled 'Na+' and 'Ca 2+'. To the left, a thermometer icon labeled 'Heat (Above 43 c)' and a purple drop labeled 'Acid (H+)' indicate triggers. To the right, red chili peppers and a pile of red powder are labeled 'Capsaicin'. On the far left, a curved arrow indicates 'Cell stimulation'. Labels for 'Cell Exterior', 'Cell Membrane', and 'Cell Interior' define the spatial context. Composite image collage themed around capsaicin and spicy foods. The background features a reddish-tinted photograph of raw red chili peppers. Overlaid on the top right is a cluster of hot sauce bottles labeled 'My stash!'. Center text reads 'ARE YOU A SPICE LOVER LIKE I AM?' and 'Ever wondered how capsaicin reduces oral burning?'. At the bottom center, there is an illustrative icon of a mouth with a tongue showing flames to visualize oral burning sensation. #### Mechanism of Capsaicin in BMS - **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 <table> <tr> <td><strong>Burning</strong></td> </tr> <tr> <td><strong>Intraoral Foreign Body Sensation</strong></td> </tr> <tr> <td><strong>Xerostomia</strong></td> </tr> <tr> <td><strong>Dysgeusia</strong></td> </tr> <tr> <td><strong>Globus pharyngeus</strong></td> </tr> <tr> <td><strong>Subjective change in tongue morphology</strong></td> </tr> <tr> <td><strong>Sialorrhea</strong></td> </tr> <tr> <td><strong>Itching</strong></td> </tr> <tr> <td><strong>Tingling sensation</strong></td> </tr> <tr> <td><strong>Occlusal Dysesthesia</strong></td> </tr> <tr> <td><strong>Oral dyskinesia</strong></td> </tr> <tr> <td><strong>Dysosmia</strong></td> </tr> <tr> <td><strong>Subjective Halitosis</strong></td> </tr> </table>   #### Dysperceptions in Patients with BMS (Adamo et al. 2023) - 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 A solid orange rectangular box containing the text 'Dysperceptions in Patients with BMS'. This serves as a title or visual label for the adjacent list of symptoms. A vertical table listing specific dysperceptions found in patients with Burning Mouth Syndrome (BMS). The list includes: Burning, Intraoral Foreign Body Sensation, Xerostomia, Dysgeusia, Globus pharyngeus, Subjective change in tongue morphology, Sialorrhea, Itching, Tingling sensation, Occlusal Dysesthesia, Oral dyskinesia, Dysosmia, and Subjective Halitosis.   Clinical photo showing a close-up of upper and lower anterior teeth in occlusion. The image demonstrates the dental condition relevant to the text's discussion of occlusal dysaesthesia or phantom bite syndrome. Clinical intraoral photograph displaying a patient's full dentition with lips retracted. The image shows the alignment of both arches, providing visual context for diagnosing occlusal abnormalities mentioned in the slide. <table> <tr> <td> <strong>ORAL MEDICINE ORAL PATHOLOGY</strong> <table style="width:100%;border-collapse:collapse;"> <tr><td> **EXAMINATION:** Porcelain fused to metal (PFM) crown/bridge. <br><strong>CASE DESCRIPTION:** Middle-aged female referred due to inability to remove foreign object stuck between teeth for 5 years. </td></tr> <tr><td> **DIAGNOSIS:** Foreign body impaction (Fish bone). </td></tr> <tr><td> **CLINICAL FEATURES:** <ul> <li>Chronic foreign body sensation.</li> <li>Inability to floss</li> <li>Referred</li> </ul> </td></tr> </table> </td> <td> <div style="display:flex;align-items:center;justify-content:center;height:100%;"> **Subject:** Middle aged male <br><strong>History:** Referred by orthodontist. <br><strong>Known History:** Wanted 3rd round of fixed orthodontics. <br><br> <strong>Subjective:** Suspected hallmarks of occlusal dysesthesia. <br><br> <strong>Investigations:</strong> <ul> <li>OC Top</li> <li>OC Bottom</li> <li>Occlusal radiograph</li> </ul> </div> </td> </tr> </table>    #### Case Study: Foreign Body Impaction - **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 Illustration of two hands holding a piece of dental floss against a pink background. The image accompanies the case description of a middle-aged female with a foreign object stuck between her teeth for 5 years that could not be removed by flossing. Line drawing diagram of four upper teeth fitted with fixed orthodontic brackets and an archwire. This visual corresponds to the case of a middle-aged male referred for suspected occlusal dysesthesia and desire for third round of orthodontics. Schematic illustration of a human mouth showing upper and lower dentures in occlusion. The diagram relates to the case of a middle-aged female complaining about poor bite from multiple dentures causing body asymmetry. <table> <thead> <tr><th>MARBACH'S DIAGNOSTIC INDICATORS OF PBS (Para-Orthodontic Belief)</th><th>MARBACH'S DIAGNOSTIC INDICATORS OF PBS (Para-Orthodontic Belief)</th></tr> </thead> <tbody> <tr> <td>Belief that severe symptoms all being due to their occlusion</td> <td>Perceived dental knowledge</td> </tr> <tr> <td>Perception of a serious bite or cosmetic defect, with frustration that multiple clinicians cannot find the problem.</td> <td>   -Often know dental jargon<br> -Will talk about their 'bite' or 'occlusal' problems, and suggest how they should be changed, or altered, to correct their problems.</td> </tr> <tr> <td>Have study casts and detailed clinical records</td> <td></td> </tr> <tr> <td>May have numerous diagnostic casts that they have accumulated over the years.</td> <td></td> </tr> <tr> <td>Many photos and documents in attempt to explain the problem</td> <td></td> </tr> <tr> <td></td> <td>Sustained delusion</td> </tr> <tr> <td></td> <td>This condition usually lasts between 10-20 years.</td> </tr> <tr> <td></td> <td>While there may be some initial placebo effect, the symptoms are rarely improved by occlusal splint therapy, orthodontics, occlusal adjustments or 'equilibration', or prosthodontic interventions of different types by different dentists or various specialists.</td> </tr> <tr> <td>May be seen more commonly in high socio-economic status patients (as they can afford to undergo repeated and extensive treatments to solve the problems), with above average intelligence who are often very articulate about what needs to be done.</td> <td></td> </tr> <tr> <td></td> <td></td> </tr> <tr> <td></td> <td>Difficulty accepting diagnosis or accepting referral to psychiatry</td> </tr> <tr> <td colspan="2">(Adapted from Kelleher, Rasaratnam and Djemal, 2017)</td> </tr> </tbody> </table>  A structured comparison table titled 'MARBACH'S DIAGNOSTIC INDICATORS OF PBS'. The table uses alternating light blue and pink columns to categorize indicators. The left column lists patient beliefs (e.g., belief symptoms are due to occlusion, perception of serious bite defect) and clinical characteristics (e.g., having study casts, photos, high socio-economic status). The right column lists corresponding behaviors and diagnostic features (e.g., perceived dental knowledge, sustained delusion lasting 10-20 years, lack of response to orthodontic interventions, difficulty accepting diagnosis). A citation '(Adapted from Kelleher, Rasaratnam and Djemal, 2017)' is present at the bottom. ### Further Reading **Kelleher, M., Rasaratnam, L. and Djemal, S., 2017. The paradoxes of phantom bite syndrome or occlusal dysaesthesia ('dysesthesia'). Dental Update, 44(1), pp.8-32.** **Tsukiyama Y, Yamada A, Kuwatsuru R, Koyano, K, 2012. Biopsychosocial assessment of occlusal dysaesthesia patients. Journal of Oral Rehabilitation, 39(8), pp.623-629.** ### Management - Difficult as patients usually remain resolutely convinced that if they could only get someone competent enough to get their 'bite right' then all their problems would be solved. - Multidisciplinary - Medical specialty care ### Case **Photographs taken by the patient herself, highlighting the occlusal contacts that she had marked herself and that she 'knew needed to be ground down'. Apparently she did this with a Dremel DIY drill because 'no dentist could see what needed to be done'. (Kelleher, Rasaratnam and Djemal, 2017)**  Four clinical intraoral photographs showing upper posterior teeth with blue occlusal marking material. The images are arranged in a 2x2 grid and depict the patient's self-identified 'high spots' on the biting surfaces of molars. These photos serve as visual evidence for the case study described in the text below, illustrating the specific areas the patient marked herself and subsequently attempted to grind down using a Dremel tool. Questions?   Photo of turbulent, churning ocean water with white foam and dark green-blue waves. Photo of calm, clear turquoise lagoon or bay with distant green hills under a blue sky. [^1]: Original PDF page 1: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=1|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.1]] [^2]: Original PDF page 2: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=2|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.2]] [^3]: Original PDF page 3: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=3|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.3]] [^4]: Original PDF page 4: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=4|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.4]] [^5]: Original PDF page 5: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=5|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.5]] [^6]: Original PDF page 6: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=6|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.6]] [^7]: Original PDF page 7: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=7|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.7]] [^8]: Original PDF page 8: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=8|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.8]] [^9]: Original PDF page 9: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=9|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.9]] [^10]: Original PDF page 10: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=10|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.10]] [^11]: Original PDF page 11: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=11|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.11]] [^12]: Original PDF page 12: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=12|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.12]] [^13]: Original PDF page 13: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=13|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.13]] [^14]: Original PDF page 14: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=14|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.14]] [^15]: Original PDF page 15: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=15|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.15]] [^16]: Original PDF page 16: [[L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD.pdf#page=16|L34 Neuropathic Orofacial Pain including Burning Mouth Syndrome DMD, p.16]] [^17]: Original PDF page 17: [[L34 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