Pain and Oral Mucosa

Home , Angular cheilitis, Burning mouth syndrome, Cheilitis, Herpes simplex, Oral allergy syndrome, Orofacial pain

VIDENSKAB & KLINIK | Oversigtsartikel

ABSTRACT Orofacial pain Local and systemic diseases that may cause conditions – pain oral mucosal pain and oral mucosa

Pain of the oral mucosa is a common ac- companying symptom of various oral mucosal lesions caused by local and systemic diseases. Anne Marie Lynge Pedersen, associate professor, ph.d., Section of Oral Pain of the oral mucosa is usually associated Medicine, Clinical Oral Physiology, Oral Pathology and Anatomy, De- partment of Odontology, Faculty of Health and Medical Sciences, Uni- with a known cause of tissue damage, e.g. versity of Copenhagen, Denmark mucosal ulcer or erosion, and it generally re- Heli Forssell, associate professor, ph.d., Department of Oral and Ma- sponds to adequate treatment and dissipates xillofacial Surgery, Institute of Dentistry, University of Turku, Finland after healing. Chronic pain, on the other hand, Bjørn Grinde, chief scientist, ph.d., Norwegian Institute of Public persists months and years after apparent tis- Health, Oslo, Norway sue healing, and attempts to alleviate pain are challenging. Neuropathic pain occurs due to damage neurogenic structures in the peripheral and/or the central nervous system. It may occur in the absence of any obvious noxious sti- atients with intermittent or persistent, painful sensa- muli, and in the oral mucosal, the pain is often tions in the oral mucosa often represent a substantial described as tingling and burning. In the oral clinical challenge with regard to diagnosis and manage- cavity, burning mouth syndrome (BMS) is pre- ment. The oral cavity is one of the most densely inner- sently considered to have neuropathic back- Pvated parts of the body, and it also has an extensive sensorimo- ground. It is important for dental practitioners tor representation in the central nervous system (CNS). The rich to have a clear understanding of the various somatosensory supply, in terms of peripheral receptors, is related diseases that can cause oral mucosal pain to to the important role of the mouth in oral sensorimotor control in provide appropriate care to patients. This pa- eating, drinking, swallowing and speaking, and also in the large per focuses on the most common local and variety of oral sensations, including pain (1-3). systemic diseases that can cause oral mucosal Acute oral mucosal pain especially occurs in association with pain with respect to their clinical features and inflammation, oral surgery or accidental injury. Most condi- management. tions with acute pain can be treated, and usually subside when healing of the tissue has taken place. Chronic pain, on the other hand, persists months and years after apparent tissue healing, and attempts to alleviate pain often fail (4). Moreover, chronic pain conditions also appear to be associated with structural and functional alterations in the CNS (5). Accordingly, early and appropriate diagnosis and management of acute pain is important in order to prevent acute pain turning into a chronic pain condition, with impaired quality of life and risk of psychological morbidity such as anxiety and depression (4). Oral mucosa pain is often characterised by a burning, stinging or sore sensation. Various mucosal lesions like ulcers, erosions and blisters are common causes of oral mucosal pain, and these lesions can occur due to a large variety of local mucosal and systemic diseases, of which some may EMNEORD be iatrogenically induced, e.g. due to sur- Orofacial pain; gical trauma, certain medications or radio- oral mucosa; burning therapy to the head and neck region. How- mouth syndrome; Communication with author: vesiculo-bullous ever, pain of the oral mucosa may also occur Anne Marie Lynge Pedersen, e-mail: [email protected] diseases in the absence of any findings such as, for

example neuropathic pain caused by damage of the peripheral CLINICAL RELEVANCE and/or central nervous system, or be of psychogenic origin. This paper presents an overview of the most common local and systemic diseases that can cause oral mucosal pain, catego- A large variety of local mu- epithelial-connective tissue rised according to their clinical characteristics and management. cosal and systemic diseases border, and has its base at are associated with pain due a deep level in the submu- Oral mucosal pain mechanisms to formation of ulcers or ero- cosa, and in some cases Oral mucosal pain is often associated with tissue damage and sions. Theses lesions differ even within the muscle or concomitant inflammation. Pain occurs as a result of activation with regard to extension in the periosteum and/or sensitisation of nociceptors on peripheral nerve fibres oral mucosa: • A mucosal erosion is de- by inflammatory mediators and by mechanical and thermal • A mucosal ulcer is defined fined as a superficial break stimuli. Two types are distinguished based on afferent fibre as a loss of surface tis- on the mucous membrane morphology. A-delta fibres are myelinated and relatively fast- sue and disintegration and with loss of the superficial conducting, but slower than mechanoreceptors. They provide necrosis of epithelial tis- epithelial cells and minor fast and sharp sensations of pain to noxious stimulation. C-fi- sue. It involves damage to damage to the underlying bres are unmyelinated and slow-conducting. They are respon- both epithelium and lamina lamina propria. It may reach sible for diffuse, dull, slow aching pain (6). They are primarily propria. It penetrates the the basement membrane. located in the connective tissue and around the subepithelial capillary plexus. The activating inflammatory mediators include bradykinin, serotonin, glutamate, and H+; the sensitising mediators include prostaglandins, serotonin, noradrenaline, cal factors. A sensation of oral burning can be associated with a nitric oxide, and nerve growth factor (6). During inflammation, large variety of systemic or local conditions of which some are nociceptors display a lower threshold for stimulation-induced reviewed in this paper (10-12) (Fig. 1 and 2). In these cases, pain or an increased sensitivity to noxious stimuli, a condition treatment of the underlying cause will often alleviate the senso- known as hyperalgesia. ry symptoms. Several local and systemic factors need therefore Oral mucosal pain may also occur in the absence of evident to be taken into consideration before the diagnosis of primary pathology or explanation, e.g. previous trauma, and is termed (idiopathic) or secondary BMS can be made. “idiopathic” pain. Neuropathic pain occurs as a result of dam- Reported prevalence rates of BMS in the general populations age neurogenic structures in the peripheral and/or the cen- vary from 0.7% to 4.6% (10). The prevalence of BMS increases tral nervous system (7), as there is not always a clear history with age, with the highest prevalence (12%) in women aged 60- of nerve injury, e.g. from local anaesthetic or surgery. After 69 (13). Very little is known of the prognosis of BMS but there is the injury, which may include direct nerve damage or tissue anecdotal evidence that BMS symptoms are long lasting. inflammation, the peripheral afferent nerve fibres react with increased excitability and spontaneous tonic activity. This may Clinical features of BMS release permanent, neuroplastic alterations in the central neu- Burning pain of the oral mucosa is the cardinal feature of pri- rons that contribute to maintain the nociceptive activity (8). mary BMS. The intensity of pain varies from mild to severe. It is most often experienced at more than one oral site, the an- Chronic neuropathic pain conditions terior part of the tongue, the anterior hard palate and the lips Conditions that may be associated with chronic neuropathic pain being most frequently affected. Pain is most often bilateral and in the oral mucosa include post traumatic trigeminal neuropa- symmetrical. Most patients experience negligible symptoms thy, trigeminal post herpetic neuralgia, and burning mouth syn- on awakening, and symptoms build up over the day, being drome (BMS), of which the latter is the predominant one. most intense in the evening, but the pain only seldom disturbs sleep. Some patients, however, experience constant symptoms Burning mouth syndrome throughout the day, while others only have intermittent symp- BMS, sometimes also called stomatodynia or glossodynia, is toms (14,15). defined as burning or painful sensations of oral mucosa with More than half of the patients complain of xerostomia no clinical signs of pathology or identifiable medical or dental (11,14). Furthermore, up to 70% of BMS patients report taste causes (9). disturbances, such as alterations in taste perception and/or dys- Considerable progress has been made in the understanding geusia (usually bitter or metallic), or phantom tastes (14,15). of BMS pathophysiology. An important step in this process has been the differentiation between primary BMS and what could Pathophysiology of BMS be called secondary BMS as its symptoms mimic primary BMS. Recent studies have revealed that several neuropathic, mainly However this condition is due to clinically identifiable etiologi- subclinical mechanisms act at different levels of the somatosen-

TANDLÆGEBLADET 2016 | 120 | NR. 3 | 213 | VIDENSKAB & KLINIK | Oversigtsartikel

Local and systemic conditions

Condition/disease Clinical features Management

Mucocutaneous diseases

Oral lichen planus (OLP) lesions often present bilaterally and are Topical or systemic corticosteroids usually seen on the buccal mucosa, the tongue and gingiva. Calcineurin inhibitors There are 6 types: Reticular, erosive/ulcerative, papular, plaque-like and bullous OLP. They may be present simul- Lichen planus (22,23) Weak evidence regarding pain relief: taneously. Topical tacromilus and pimecrolimus The reticular type is the most common one and usually Topical ciclosporin asymptomatic, whereas the erosive/ulcerative types often Topical aloe vera accompanied by a burning, stinging pain.

An autoimmune disorder with deposition of mainly IgG class Systemic treatment including corticoste- antibodies intercellularly as well as damage to desmosomes roids, immunoglobulins, rituximab, myc- Pemphigus vulgaris by antibodies directed against the extracellular domains of ophenolate mofetil, (24) cadherin-type epithelial cell adhesion molecules, particularly methotrexate, azathioprine, and cyclophos- desmoglein 3, resulting in multiple ulcers and erosions prece- phamide ded by bullae, mainly on the soft palate and buccal mucosa.

Topical steroids such as clobetasol An acute or chronic autoimmune disease, occurring due Systemic prednisone to reaction to the epithelial basement membrane, causing Other immunosuppressive agents e.g. met- Mucous membrane desquamation and ulceration of the oral mucosa. The most hotrexate, azathioprine, mycophenolate pemphigoid (25) common sites of oral involvement are the gingiva (94%), mofetil may be indicated. Antibiotics, e.g. palate (32%), buccal mucosa (29%), floor of the mouth (5%), tetracycline or erythromycin to control se- and tongue (5%). condary infections

Identification of triggering agent Acute onset; extensive, irregular and extremely painful areas If HSV infection, antiviral therapy of ulcerations with yellow base and erythematous borders If it is an adverse drug reaction, the drug is on buccal mucosa, palate, dorsal and ventral surfaces of immediately stopped. Palliative treatment: Erythema multiforme the tongue. analgesics, viscous lidocaine rinses, soothing (26) The lips are often involved showing extensive irregular ul- mouth rinses, soft diet, avoidance of acidic cerations, cracking and fissuring with blood encrustation. and spicy food, systemic or topical antibiotics Erythema multiforme is usually triggered by herpes simplex to prevent secondary infection; systemic or infections, and occasionally by drug intake. topical corticosteroids in severe cases

Erythematous and ulcerative lesions with white striae radia- Lupus erythematosus ting from the centre, on buccal and labial mucosa, gingiva Systemic or topical corticosteroids (25) and vermillion. Systemic immunosuppressive agents The lesions can also be white or red patches or bullous.

Iatrogenic conditions

Characterised by lichenoid, papular and erythematous lesions, and occasionally ulcerations and desquamation on the buccal and labial mucosa, the palate and dorsal part of the Oral Graft versus host tongue. The oral lesions are often accompanied by fever, Systemic immunosuppressive agents Disease (27) malaise, nausea, and xerostomia. The oral findings may be caused by a combination of radiotherapy, chemotherapy, immunosuppressive medications, and secondary infections.

A condition that may occur in patients who receive high-dose Palliative treatment: chemotherapy, and/or radiotherapy to head and neck cancer Maintenance of sufficient oral hygiene involving the oral cavity. Oral mucositis refers to erythema- Sip plenty of water tous and ulcerative lesions of the oral mucosa. The lesions Analgesics, viscous lidocaine rinses Oral mucositis (28) are often very painful and compromise nutrition and oral hy- Lubricating, soothing mouth rinses/gels giene as well as increase risk for local and systemic infection. Soft diet, avoidance of alcohol, acidic and The condition may also be accompanied by taste distur- spicy food bances and xerostomia. Systemic or topical antibiotics (antibacterial, Acute mucositis may progress into chronic mucositis. antiviral and antifungal treatment)

Discontinuing use of the offending medication, Often extensive irregular ulcerations of variable depth, most which could be NSAIDs, penicillamine, pyrazo- Medication-induced commonly seen on the buccal mucosa and gingiva. lone; antihypertensives like captopril and beta- reactions (26) Erosions as well as pemphigus-like and lichenoid lesions blockers; antibiotics e.g. penicillin, rifampin and may also be present. cephalexin; barbiturates and hormones. Topical steroids to enhance healing

Oral allergy syndrome (OAS) usually occurs in patients who are allergic to pollen from trees, grasses or weeds. Fresh fru- it, raw vegetables and raw nuts are common causes of OAS. Avoidance of the allergens The symptoms including itching sensation and/or swelling of Oral allergy syndrome Identification of cause of the allergy by patch all or part of the lips, tongue, mouth or throat, but this can on and contact allergy testing occasions be severe and also include nausea and vomiting. (29) Systemic or topical corticosteroids Dental materials, oral hygiene products and food additives Antihistamine may cause contact allergic reactions in the mouth with varied clinical presentation including stomatitis, lichenoid lesions, erosions, blisters and ulcerations.

Local mucosal conditions

RAS is characterised by recurrent bouts of solitary or multiple Potential systemic association with RAS shallow painful ulcers with erythematous borders, at intervals must be ruled out, especially in cases with of few months to few days. Ulcers are most commonly seen sudden development of RAS in adulthood Reccurent aphthous in the non-keratinised mucosal surfaces like labial mucosa, Chlorhexidine mouth rinse stomatitis (RAS) (30) buccal mucosa, and floor of the mouth. Topical steroids and systemic prednisone in Ulcers may be 2-5 mm in diameter (minor RAS), > 10 mm severe cases (major RAS). Tetracycline oral suspension

Mineral and vitamin deficienies

Atrophic glossitis in which the filiform papilla of the dorsum of the tongue undergo atrophy, leaving a smooth, erythe- Iron and vitamin B12 and folate deficiencies matous tongue. Other parts of the oral mucosa may also often occur due to malabsorption in gas- appear atrophic and red. trointestinal diseases or due to pernicious Iron deficiency Aphthous-like ulcers are common in severe cases. anaemia Vitamin B12 and folate Burning, stinging sensation may precede clinically detectable The oral manifestations are often responsive deficiencies (32) oral lesions. to appropriate replacement therapy. In se- Severe cases of vitamin B12 deficiency may also be asso- vere cases of vitamin B12 deficiency, pares- ciated with paresthesia. thesia may persist Predisposition to develop angular cheilitis.

Circular erythematous areas, often sharply defined by elevated, whitish border zones, located at the lateral, dorsal, anterior, and/ Symptomatic treatment: Geographic tongue or ventral parts of the tongue. The erythematous appearance Benzydamine hydrochloride (31) occurs due to atrophy and loss of filiform papillae lesions. Soothing mouth rinse About 30% have oral discomfort, burning and stinging sen- Topical steroids in severe cases sation on the tongue.

Anywhere on the oral mucosa. Removal of cause Localised ulcers with red borders produced by accenditial Traumatic ulcers Heals in 7-10 days unless secondarily in- biting of oral mucosa, pentration by a foreign object or ir- fected rition by a denture dental restoration orthodontic applienes.

Inflammatory bowel diseases

Systemic treatment with immunosuppres- Multifocal, linear, nodular, or diffuse mucosal thickenings sants seen in the labial and buccal mucosa, and the mucobuccal Crohn’s disease (32) Some oral ulcerating lesions may require to- folds. They may be associated with (persistent) ulcerations. pical corticosteroid therapy or intralesional Aphthous-like ulcerations and atrophic glossitis. corticosteroid injections

The oral lesions usually respond to the sy- Scattered, clumped or linearly oriented pustules on an ery- stemic treatment thematous mucosa at multiple oral sites. Topical or systemic corticosteroids and dap- Ulcerative colitis (32) Some patients exhibit oral aphthous-like lesions in addition sone have been used for recalcitrant oral le- to the pustular lesions. sions with variable effectiveness

Gluten-free diet Aphthous-like ulcers are common. Aphthous-like lesions usually disappear or Coeliac disease (33) Malabsorption of iron and vitamin B may lead to burning, improve in patients who adhere to a gluten- stinging sensations in the tongue. free diet

Table 1. Clinical features and principles of management of local and systemic conditions causing oral mucosal ulcers, erosions and blisters. Tabel 1. Kliniske manifestationer og behandlingsmæssige tiltag i forbindelse med lokale og systemiske sygdomme, som forårsager sår, erosioner og blærer i mundslimhinden.

TANDLÆGEBLADET 2016 | 120 | NR. 3 | 215 | VIDENSKAB & KLINIK | Oversigtsartikel

Oral lichen planus Deep tongue fissures

Fig. 2. 74-year old female with oral lichen planus. She was referred due to itching and burning sensation of the dorsal part of her tongue, especially in relation to intake of spicy and acidic food. Note the reticular whitish striae on the tongue. Fig. 1. 32-year old female with deep fissures on the dorsal She also had a history of small ulcerations on the marginal and marginal parts of her tongue as well as a geographic part of the tongue. tongue. She complained of intermittent tingling and burning sensation on her tongue. Fig. 2. 74-årig kvinde med oral lichen planus. Patienten var henvist pga. stikkende og brændende fornemmelse Fig. 1. 32-årig kvinde med dybe fissurer på tungeryggen og på tungeryggen, især i forbindelse med indtagelse af kry- tungens siderande samt geografisk tunge. Hun havde klager drede og syrlige fødeemner. Bemærk de retikulære, hvidlige over stikkende og brændende fornemmelse på tungen. stregtegninger på tungen. Ifølge anamnese havde patienten også haft problemer med små ulcerationer på tungens side rande. sory system and contribute to the pathophysiology of primary BMS (12,16). Some studies have demonstrated that small-fibre mediated neuropathy is a common finding in BMS and that ap- as cognitive behavioural group therapy (21). The topical use of proximately a fifth of BMS patients show subclinical trigeminal clonazepam (1 mg three times a day) improves the symptoms nerve lesions (10,14). Furthermore, several electrogustometric in about two thirds of the patients (presumably in patients studies have reported evidence for chorda tympani hypofunc- whose symptoms is due to peripheral neuropathy), and is the tion in BMS (17). first choice for treatment when medication is needed. As the Central nervous system pathology seems also to be in- present understanding of BMS pathophysiology suggest neuro- volved in the generation of BMS symptoms. A study on cer- pathic involvement, also drugs that are effective in other neu- ebral reorganization demonstrated altered grey and white ropathic pain conditions, such as tricyclic antidepressants or matter volumes and altered functional connectivity patterns gabapentinoids, can be used for BMS. in BMS (18). Two positron emission tomography (PET) studies have demonstrated a decline in endogenous dopamine lev- Conditions causing pain due to mucosal tissue injury and els in BMS, suggesting deficiencies in central pain modulation inflammation (19,20). Painful oral mucosal ulcers, erosions and blisters may occur due to a large variety of diseases. Table 1 gives an overview of lo- Management of BMS cal and systemic diseases causing mucosal ulcers, erosions or First of all, it is important that dentists recognize the syndrome, blisters due to various inflammatory reactions, autoimmune- give a credible explanation of the current understanding of mediated epithelial damage (e.g. mucous membrane pemphi- the pathophysiological mechanisms of BMS, and reassure the goid), immune deficiency, and mucosal trauma. The table also patient of its benign nature. Reassurance alone can suffice in indicates principles of management. some cases, and lead to symptom resolution and /or better cop- ing. Some patients experience pain alleviation while eating, Oral infections chewing gum, sucking pastilles, drinking cold beverages, or by A number of bacterial, fungal and viral infections may also avoiding spicy foods (15). As regards the actual therapies for cause oral discomfort and pain due to formation of vesicles, BMS there is some evidence from RCTs for the effectiveness of blisters, erosions and ulcers. The most common infections and topical clonazepam and antioxidant alpha-lipoid acid, as well their management are described in Table 2.

Fungal and viral infections

Bacterial and Clinical features Management fungal infections

Oral hygiene instructions Acute necrotising Painful, bleeding gingiva characterised by necrosis and ul- Chlorhexidine mouth rinse ulcerative gingivitis/ ceration of gingival papillae and margins. Analgesics stomatitis Foetor ex ore. Treatment of underlying disease

Common fungal infection, predominantly caused by Candida albicans. Usually occurs when the oral homeostasis is disturbed; na- mely in relation to treatment with antibiotics, corticosteroids, Topical antifungal agents: or cytotoxic drugs; or as a consequence of diabetes, salivary Nystatin gland hypofunction, and immunosuppression. Miconazole Erythematous candidosis: generalised erythema and pain. Systemic fluconazole Oral candidosis (36) When present on the tongue, the Median rhomboid glossitis, when present on the tongue. Chlorhexidine mouth rinse Pseudomembranous type: white patches that are easily wi- Treatment of underlying condition ped off leaving erythematous, bleeding, sore surface. Angular cheilitis: sore cracks and redness at angle of mouth. Xerostomia, burning, stinging and itching sensations, and metal taste are common symptoms.

Viral infections

Multiple labial and intraoral vesicles that coalesce, then rup- Antiviral treatment is generally not used for Primary herpetic gin- ture and form ulcers. the oral lesions, but systemic antiviral medi- givostomatitis (37,38) Acute gingivitis, foetor ex ore, the oral mucosa may have cation is an option. Maintenance of good oral generalised erythema. hygiene, chlorhexidine mouth rinse

Local or systemic use of anti-herpes medica- Recurrent herpes Eruption of vesicles, that may coalesce, rupture and crust. tion (e.g., acyclovir or valacyclovir), preferably labialis (38) in early phase

Small vesicles on the oral mucosa that rupture and form Chickenpox (varicella- shallow ulcers. Antiviral treatment is rarely used zoster virus) (38) Generalised erythematous oral mucosa.

Unilateral eruption of vesicles that form ulcers on the buccal, Antiviral therapy in the acute phase is impor- Herpes zoster (reac- gingival, palatal or lingual mucosa in linear pattern following tant to avoid postherpetic neuralgia. tivation of varicella- sensory distribution of trigeminal nerve. Postherpetic neuralgia: TCA, gabapentin or zoster virus) (38) Postherpetic neuralgia is common (neuropathic pain). Gra- pregabalin dual healing without scarring.

Various secondary oral infections (candidiasis in particular) Anti-HIV treatment warranted, as well as tre- HIV (38) are an early sign of AIDS. Herpes simplex and herpes zoster atment of secondary infections may also occur and cause oral pain.

Herpangina (38) Oropharyngeal vesicles that coalesce, then rupture and form (Coxsackie virus A No antiviral medication is available ulcers. and echovirus)

Hand, foot, and mouth syndrome Oropharyngeal vesicles that rupture and become painful No antiviral medication is available (type A Coxsackie shallow ulcers. Primarily affects children. viruses) (38)

Papilloma virus Single or multiple papillary lesions. Cauliflower lesions cove- Currently no antiviral treatment available (38,39) red with normal-coloured mucosa.

Cause mononucleosis, which may involve sore throat and Epstein-Barr virus numerous small ulcers that precede lymphadenopathy. Gin- Antiviral treatment generally not used (35) gival bleeding, petechiae at the border between soft and hard palate.

Table 2. Clinical features and principles of treatment of bacterial and fungal and viral infections associated with oral mucosal pain. Tabel 2. Kliniske manifestationer og behandling af bakterielle, svampe- og virale infektioner, som er ledsaget af smerter i mundslimhinden.

TANDLÆGEBLADET 2016 | 120 | NR. 3 | 217 | VIDENSKAB & KLINIK | Oversigtsartikel

The oral cavity plays a key role in the life strategy of several Conclusions viruses. Mucous membranes (being wet and surfaced by live There are many different causes of oral mucosal pain and many cells) are generally easier to penetrate than intact skin, and the of them often present with similar clinical features and symp- location has obvious qualities in terms of access and transmis- toms which make diagnosis difficult to achieve. However, it is sion (34). A majority of people harbour at least one of the two important that these patients are properly diagnosed in order herpes simplex viruses (HSV), of which type 1 is the one more to initiate an adequate treatment. The diagnosis and treatment often associated with the mouth (Table 2). A recent case report of patients with chronic oral mucosal pain like BMS, is often suggests that HSV-1 can be responsible for BMS-like symptoms more challenging and generally requires a multidisciplinary ap- (35). The patient had a high titre of the virus in saliva, and the proach. pain disappeared upon antiviral treatment.

ABSTRACT (DANSK)

Oro-faciale smertetilstande – smerte og oral mucosa kan påvises objektiv årsag, og den orale smerte beskrives ofte En lang række mundslimhindeforandringer forårsaget af lokale som en brændende og stikkende fornemmelse i mundslimhin- eller systemiske faktorer kan være ledsaget af smerter. Smerter den. Nyere forskning tyder på, at kronisk mundbrand, burning i mundslimhinden er normalt forbundet med vævsbeskadigelse, mouth syndrome (BMS), er en neuropatisk smertetilstand. Det fx sår eller erosion, og disse responderer sædvanligvis med he- er vigtigt for tandlæger at have en viden og forståelse af de ling efter adækvat behandling. Kronisk smerte derimod fortsæt- forskellige sygdomme, der kan forårsage smerter i mundslim- ter måneder og år efter tilsyneladende vævsheling, og forsøg hinden for derved at yde den optimale behandling. Denne arti- på at lindre smerterne kan være udfordrende. Neuropatiske kel fokuserer på de mest almindelige lokale og systemiske syg- smerter opstår som følge af beskadigelser på det perifere og/el- domme, der kan forårsage smerter i mundslimhinden, herunder ler centrale nervesystem. Smerten kan forekomme, uden at der deres kliniske manifestationer og behandling.

Literature 1. Haggard P, de Boer L. Oral soma- Surg Clin North Am 2008;20:237- 2015;42:300-22. prefrontal cortex in patients with tosensory awareness. Neurosci- 54. 13. Bergdahl M, Bergdahl J. Burning burning mouth syndrome. Pain ence & Biobehavioral Reviews 8. Wolff C. Central sensitization: mouth syndrome: prevalence and 2014;155:1472-80. 2014;47:469-84. Implications for the diagnosis and associated factors. J Oral Pathol 19. Jääskeläinen SK, Rinne JO, 2. Jacobs R, Wu CH, Goossens K et treatment of pain. Pain 2011;152 Med 1999;28:350-4. Forssell H et al. Role of the dopa- al. Oral mucosal versus cutane- (3 Supp):S2-15. 14. Grushka M. Clinical features minergic system in chronic pain ous sensory testing: a review 9. HEADACHE CLASSIFICATION of burning mouth syndrome. - a fluorodopa-PET study. Pain of the literature. J Oral Rehabil COMMITTE OF THE INTERNA- Oral Surg Oral Med Oral Pathol. 2001;90:257-60. 2002;29:923-50. TIONAL HEADACHE SOCIETY 1987;63:30-6. 20. Hagelberg N, Forssell H, Rinne JO 3. Sessle BJ. Mechanisms of oral so- (IHS). The international classifi- 15. Forssell H, Teerijoki-Oksa T, Koti- et al. Striatal dopamine D1 and matosensory and motor functions cation of headache disorders. 3rd ranta U et al. Pain and pain behav- D2 receptors in burning mouth and their clinical correlates. J Oral ed. Cephalalgia 2013;33:629-808. ior in burning mouth syndrome: syndrome. Pain 2003;101:149-54. Rehabil 2006;33:243-61. 10. Scala A, Checchi L, Montevecchi a pain dairy study. J Orofac Pain 21. Zakrzewska JM, Forssell H, 4. Zakrzewska JM. Multi-dimen- M et al. Update on burning mouth 2012;26:117-25. Glenny AM. Interventions for sionality of chronic pain of the syndrome: overview and patient 16. Jääskelainen SK. Pathophysiol- the treatment of burning mouth oral cavity and face. J Headache management. Crit Rev Oral Biol ogy of primary burning mouth syndrome. Cochrane Database Pain 2013;14:37. Med 2003;14:275-91. syndrome. Clin Neurophysiol of Systematic rewievs 2005. Jan 5. Sessle BJ. Peripheral and central 11. Pedersen AML, Smidt D, 2012;123:71-7. 25;(1).: CD002779. mechanisms of orofacial inflam- Nauntofte B et al. Burning Mouth 17. Kolkka-Palomaa M, Jääskeläinen 22. Scully C, Carrozzo M. Oral mu- matory pain. Int Rev Neurobiol Syndrome: Etiopathogenic Mech- SK, Laine MA et al. Pathophysiol- cosal disease: Lichen planus. Br J 2011;97:179-206. anisms, Symptomatology, Diagno- ogy of primary burning mouth Oral Maxillofac Surg 2008;46:15- 6. Svensson P, Sessle B. Orofacial sis and Therapeutic Approaches. syndrome with special focus 21. pain. In: Miles TS, Nauntofte B, Oral BioSci Med 2004;1:3-19. on taste dysfunction: a review. 23. Lodi G, Carrozzo M, Furness S et Svensson P, eds. Clinical Oral 12. Forssell H, Jääskeläinen S, List T Oral Diseases 2015 May 11. doi: al. Interventions for treating oral Physiology, 1st ed. Copenhagen: et al. An update on pathophysi- 10.1111/odi.12345. [Epub ahead lichen planus: a systematic review. Quintessence Publishing 2004; ological mechanisms related to of print] Br. J Dermatol 2012;166:938-47. 93-119. idiopathic oro-facial pain con- 18. Khan SA, Keaser ML, Meiller TF et 24. Scully C, Challacombe SJ. 7. Benoliel R1, Eliav E. Neuropathic ditions with implications for al. Altered structure and function Pemphigus vulgaris: Update on orofacial pain. Oral Maxillofac management. J Oral Rehabil in the hippocampus and medial etiopathogenesis, oral manifesta-

tions and management. Crit Rev 27. Kuten-Shorrer M, Woo SB, Tre- matitis. Clinics in Dermatology association with gluten-free diet Oral Biol Med 2002;13:397-408. ister NS. Oral graft-versus-host 2000;18:569-78. in children. Digestive and Liver 25. Eversole LR. Immunopathology disease. Dent Clin North Am. 31. Assimakopoulos D, Patrikakos G, Disease 2008;40:104-7. of oral mucosal ulcerative, des- 2014;58:351-68. Fotika C et al. Benign migratory 34. Grinde B. Herpesviruses: latency quamative, and bullous diseases: 28. Lalla RV, Sonis ST, Peterson DE. glossitis or geographic tongue: an and reactivation - viral strategies Selective review of the literature. Management of oral mucositis in enigmatic oral lesion. Am J Med and host response. J Oral Micro- Oral Surg Oral Med Oral Pathol patients with cancer. Dent Clin 2002;113:751-5. biol 2013;5. doi: 10.3402/jom. 1994;77:555-71. North Am 2008;52:61-viii. 32. Daley DT, Armstrong JE. Oral v5i0.22766. 26. Joseph TI, Vargheese G, George D 29. Larsen KR, Johansen JD, Reibel J manifestations of gastrointesti- 35. Nagel MA, Choe A, Traktinskiy I et al. Drug induced oral erythema et al. Dentalmaterialer kan udløse nal diseases. Can J Gastroenterol et al. Burning mouth syndrome multiforme: A rare and less recog- orale allergiske reaktioner. Ug- 2007;21:241-4. due to herpes simplex virus nized variant of erythema multi- eskrift for Læger 2013;175:1785-9. 33. Campisi G, Di Liberto C, Carroccio type 1. BMJ Case Rep 2015 Apr forme. J Oral Maxillofac Pathol 30. Porter SR, Hegarty A, Kaliakatsou A et al. Coeliac disease: Oral ulcer 1;2015. pii: bcr2015209488. doi: 2012;16:145-8. F et al. Recurrent aphthous sto- prevalence, assessment of risk and 10.1136/bcr-2015-209488.

The complete reference list can be send upon request by contacting the first author.

TANDLÆGEBLADET 2016 | 120 | NR. 3 | 219 |