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Pain and Oral Mucosa 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 oc- cur 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 impor- tant 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, sting- ing or sore sensation. Various mucosal lesions like ulcers, ero- sions 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 | 212 | TANDLÆGEBLADET 2016 | 120 | NR. 3 Pain and oral mucosa | VIDENSKAB & KLINIK 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 in- clude 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
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