|Year : 2015 | Volume
| Issue : 3 | Page : 127-134
Orofacial pain: A critical appraisal in management
Shatavisa Mukherjee1, Sukanta Sen1, Satwika Sinha2
1 Department of Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
2 Department of Biochemistry, Calcutta National Medical College and Hospital, Kolkata, West Bengal, India
|Date of Web Publication||21-Sep-2015|
Dr. Sukanta Sen
Department of Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata - 700 073, West Bengal
Source of Support: None, Conflict of Interest: None
Orofacial pain (OFP), a highly debilitating and prevalent pain condition, is a major concern of national public health. OFP can arise from different regions and etiologies. This intractable pain condition, arising from oral structures innervated by trigeminal nerves, represent a challenge to the clinician as the pain has multiple sources of origin and range of etiologies, thus making the diagnosis very challenging. Odontalgia, temporomandibular disorders (TMD), trigeminal neuropathy and migraines are some common disorders for which patients seek treatment. Owing to its diverse classification and etiologies, proper identification of the condition and subsequent treatment approaches has become a necessity. A multidisciplinary treatment approach comprising patient education, pharmacological, non-pharmacological means and psychosocial interventions can be considered essential for this enfeebling condition.
Keywords: Chronic pain, neuropathic pain, orofacial pain, pain management
|How to cite this article:|
Mukherjee S, Sen S, Sinha S. Orofacial pain: A critical appraisal in management. Indian J Pain 2015;29:127-34
| Introduction|| |
Pain, a highly subjective experience, involves the peripheral and central nervous system and is influenced by previous experiences, emotional and cognitive factors. The International Association for the Study of Pain's (IASP) widely used definition states: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."  Pain could also be viewed as a protective or defensive mechanism that sends the brain an alert so a protective behavior can be generated. Nevertheless in chronic pain this purpose is missing. When pain lasts longer than it is supposed after healing has happened, it can in fact turn to be an etiologic factor. Therefore pain cannot be viewed only as a sign or a symptom of a disease. This finding has a profound impact in the way chronic pain should be viewed by health care providers. Also it should create a shift in patient's behavior towards pain management. Treating pain is thus not only a palliative or supportive care. Pain can cause transient or irreversible changes in the peripheral and central nervous system, clinically resulting in myofascial pain, neuropathic pain and other complex pain syndromes. 
Chronic orofacial pain (OFP) comprises a heterogeneous group of disorders that cause ongoing pain in the head and face region. There are many patients who complain about intractable OFP. Developing therapeutic strategies for OFP disorders, exact knowledge of trigeminal mechanism of pain and nociception is thus indispensible. OFP is a highly prevalent and debilitating condition. For example, in the United States, one report estimated that 22% of the general population had suffered from some form of facial pain at some point in the six-month period before questioning, of which 12% was toothache. In the United Kingdom, 7% of the general population reported having some degree of chronic OFP. Other reports indicate a prevalence of 10-15% for TMD in the general population. 
OFP is a general term covering any pain localized to the region above the neck, in front of the ears and below the orbitomeatal line, as well as pain within the oral cavity; pain of dental origin and temporomandibular disorders (TMD). OFP is a common symptom having a range of etiologies. It is estimated that over 95% of cases of OFP result from dental causes i. e., toothache caused by pulpitis or a dental abscess. The second most common cause of OFP is temporomandibular joint (TMJ) disorders. All other causes of OFP are rare in comparison, although the full differential diagnosis is quite extensive. Conditions when OFP is persistent for three months or longer, is often referred as chronic OFP.
The OFP classification as outlined by Okeson ,, is divided into physical (Axis 1) and psychological (Axis 2) conditions. Physical conditions comprise TMD, which include disorders of the TMJ and disorders of the musculoskeletal structures (e. g., masticatory muscles and cervical spine); neuropathic pains, which include episodic (e. g., trigeminal neuralgia [TN]) and continuous (e. g., peripheral/centralized mediated) pains and neurovascular disorders (e. g., migraine). Psychological conditions include mood and anxiety disorders.
| Mechanisms Behind OFP|| |
Orofacial structures consist of several nerves innervating facial skin, teeth, tongue, masticatory muscles, TMJ and salivary glands. During food ingestion, orofacial structures receive frequent stimulation, which is necessary for ingestive behavior such as mastication, salivation and swallowing requiring coordination of both peripheral and central nervous systems.  The trigeminal nerves innervating the oral structures, i. e., oral nerves, relay their sensory information in the dorsomedial fields of trigeminal sensory nuclei (TSN). Neurons in this region also receive direct cortical projections primarily in the dorsomedial fields. Similarly, corticospinal projection is found mostly in the dorsomedial fields in the spinal dorsal horn, where primary afferents from the body extremities terminate. The TSN neurons, which receive primary afferent inputs from the oral nerves, might be highly developed to perform processing and integration of the ascending and descending somatosensory signals generated during food ingestion. Abnormal pain related behavior is interpreted as a sign of neuropathic pain such as hyperalgesia, allodynia and phantom pain. In the spinal system, transection of a peripheral nerve or dorsal root causes a hypersensitivity of deafferented dorsal horn neurons to noxious stimulation of a nearby denervated skin area within the same dermatome. Such a hypersensitivity of deafferented second order neurons may underlie the hyperalgesia at the edge of the denervated skin area. On the other hand, transection of the inferior alveolar nerve (IAN) induces hypersensitivity of TSN neurons outside the deafferented IAN's territory. IAN transection causes hyperalgesia of the upper lip skin, which is outside the denervated mandibular branchial arch. 
They are the most common cause of lower face pain. The most challenging dental diagnosis is that of the cracked tooth as this can be very difficult to detect leading the symptoms to become chronic. Sophisticated imaging measures such as cone beam computed tomography (CT) may be helpful. Dental pain needs to be treated mechanically together with analgesics and in some cases antibiotics.
Intraoral non-dental pain
Unrelated to the dental tissues, there are other causes of dental pain within the oral cavity. Oral mucosal lesions such as recurrent oral ulceration, blistering conditions causes chronic pain. Salivary stones cause intermittent pain of relatively low intensity. In some cases, there exists a clear history of nerve damage due to dental procedures or trauma, while for most cases the underlying mechanism remains unclear. This has led to some confusing nomenclature. Recently an international group of experts  proposed the use of the term persistent dentoalveolar pain disorder to encompass persistent pain without local disease, and the symptoms were proposed to be subdivided into those where there is a clear relationship to some form of trauma and others where the mechanism is unknown. Attempts have been made to determine patients' experience of this pain and some common themes has emerged e. g., difficult to obtain a clear history, complex descriptors and well-localized deep pain. Terms such as post-traumatic trigeminal neuropathy, peripheral painful traumatic trigeminal neuropathy (PPTTN) could then be used in those instances where there is a clear correlation between trauma and development of pain.
Burning mouth syndrome/glossodynia
This intraoral condition presents as a burning discomfort of the oral mucosa especially the tongue, for which local or systemic causes were missing. It is especially common in postmenopausal women who have been found to have a high level of anxiety and depression. Neurophysiological testing and biopsies of the tongue reveal peripheral nerve changes with abnormal appreciation of temperature, while functional magnetic resonance imaging (fMRI) tests reveal central changes. Symptoms range from altered taste, disturbed salivary production to various other abnormal sensations. The symptoms can be continuous but the intensity does vary throughout the day and some patients find eating mild food helpful. On examination, the oral mucosa is found persistent with signs of fissured tongue at times. Investigations are needed to exclude other causes of burning.
As a part of pharmacological management strategies, Clonazepam has been evaluated as a topical and systemic agent with mixed outcomes though its side effects should also be well-considered. Several trials have reported conflicting outcomes on the use of alpha-lipoic acid, an antioxidant.  With evidence that this is a potential neuropathic pain, drugs for neuropathic pain like gabapentin, pregabalin and tricyclic antidepressants (TCAs) can also be tried.
TMD, the most common cause of non-dental pain includes disorders of the TMJ and disorders of the musculoskeletal structures (e. g., masticatory muscles and cervical spine). , Though principally an extra oral pain, it is often felt in the retromolar area. The patient may present with jaw ache, earache, toothache, facial pain and/or headache; however, the complaint may be as benign as general facial fullness or pressure. Most epidemiological studies clearly demonstrate that TMD symptoms are more commonly seen in women than in men.  Treatment planning depends on various factors, including the chief complaint, medical history, presenting symptoms, examination and diagnosis. According to the new proposals of Research Diagnostic Criteria (RDC),  the commonest condition will be called myalgia and the criteria are: Pain in the muscle affected by jaw movement and palpation of the masseter or temporalis induces the same pain. Treatment may include, rest, hot or cold compresses, stretching exercises, and muscle relaxants. If the pain radiates to other local structures, then it will be termed myofascial pain with referral. Blocking the source of the pain (i. e., masseter muscle) by using a vapocoolant spray or local anesthetic injection can also provide a definitive diagnosis. Myositis, a localized transient swelling involving the muscle and facial tissues, tends to be increased pain with mandibular movement and localized tenderness usually following injury or infection. 
TMD assessment should include a general examination of the head and neck, a detailed examination of the masticatory muscles, an evaluation of the TMJs, an evaluation of mandibular range of motion (ROM) and a detailed intraoral examination.  Disorders of the disc-condyle incoordination lead to clicks, pops and crepitus. These sounds are evaluated with the help of a stethoscope placed in the TMJ area or sometimes perceived during palpation. Clicks and pops are commonly related to disc displacements with reduction and crepitation is commonly associated with osteoarthritic changes in the articular surfaces of the TMJ.  Imaging of the TMJ may also be useful during examination. Patient's opening and locking patterns should be viewed to note any to note any mandibular deviations. The evaluation of mandibular ROM consists of measuring comfort opening, active opening, passive opening, protrusion, and left and right lateral excursions with a millimeter ruler while noting the severity and location of pain with jaw movement. This helps in differentiating between joint and muscle pain.  Comfort opening is determined by the patient opening as wide as possible without any pain, active opening is determined by the patient opening as wide as possible with pain, and passive opening is determined by the clinician gently stretching the patient presumably past active opening while noting a soft or hard end feel. An inter-incisal distance of approximately 40 mm or the width of three of the patient's fingers is regarded as normal. The occurrence of TMJ clicking, crepitus or jaw opening interferences with or without pain should also be noted at the initial examination as these baseline findings will aid in establishing the differential diagnosis and treatment options, as well as providing a comparison for future change in TMD symptoms. Degenerative disorders, joint dislocations as often found in hyper- or hypomobility conditions do not cause significant pain. TMD pain is now found to be related to other conditions such as fibromyalgia, back pain and migraine. Some headaches are also proposed to be due to TMD in that jaw movement induces the same headache.
A wide range of therapies are used but overall self-management through education, physiotherapy and with some cognitive behavior therapy needs to be encouraged. It has been shown that patients have reported feeling less pain immediately after their initial patient education/counseling visit, perhaps as a consequence of an immediate reduction in stress/tension-related parafunctional activity. Patient education is a crucial aspect of home care and is one of the most subtle and underappreciated, yet effective, treatments for TMD. A successful home care program consists of resting the masticatory muscles by limiting jaw movements, parafunctional habit modification, emphasizing a soft diet and moist heat and/or ice therapy. 
Non-surgical medical care involves physical therapy. Primary goals of the physical therapy component of treatment are to stretch chronically contracted and fatigued muscles, increase ROM, and reduce muscular trigger point activity.  A number of exercises are commonly used to treat TMJ-associated muscle disorders, including N-stretch (placing the tip of the tongue on the roof of the mouth and stretching the jaw), chin to chest (gently pulling the head forward, bringing the chin toward the chest); and head tilt (turning the head to one side and then tilting it posteriorly). These exercises done four to six times per day seem to be effective. In addition, the patient should use moist heat for 10-15 minutes followed by ethyl chloride spray prior to stretching the muscles. Vapocoolant spray provides a temporary anesthesia effect to the muscles so that a more intense stretch can be achieved without pain. Transcutaneous electrical nerve stimulation has shown even higher success rates. Medications are an effective addition in managing the symptomatology of intracapsular disorders.
Commonly used pharmacological agents for the treatment of TMJ disorders include analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics, oral and injectable corticosteroids, sodium hyaluronate injections, muscle relaxants, botulinum toxin injections and antidepressants.  The analgesics and corticosteroids are indicated for acute TMD pain; the NSAIDs, local anesthetics and muscle relaxants are used for both acute and chronic conditions; and TCA are usually used more for chronic TMD pain in association with tension-type headaches. Intracapsular injection of corticosteroids significantly reduces TMJ pain. The use of triamcinolone or dexamethasone, in addition to 2% lidocaine without epinephrine, is generally used for TMJ injections.  TCAs are useful for most OFP, including musculoskeletal pains, neuropathic pains, migraine and tension-type headache. The newer SNRIs, venlafaxine, duloxetine and desvenlafaxine, are used increasingly for chronic pain, and particularly neuropathic pain. Research demonstrating the efficacy of botulinum toxin for muscular disorders related to TMD is limited, although there is some data to support the benefit of using low concentrations and large injection volumes of botulinum toxin at multiple muscular sites.  Oral stabilization appliances such as flat plane splint and anterior repositioning splint are often used as adjunct therapy for TMD. 
A variety of surgical procedures, including arthrocentesis, arthroscopy and arthrotomy can also be used in the presence of any functional signs. Arthrocentesis, a conservative treatment involving an intra-articular lavage with or without deposit of corticosteroids, is useful when there are intra-articular restrictions to movement, as in disc displacement without reduction.  Arthroscopy is a closed surgical procedure that allows direct observation and sampling of joint tissue, useful in hypomobility due to joint derangement as well as fibrosis.  Arthrotomy is an open surgical procedure that modifies joint anatomy, such as total or partial joint reconstruction or replacement, which is required for the patient who has advanced TMD that meets the surgical criteria. Acupuncture appears to be a beneficial treatment in conjunction with traditional therapies for TMD and perhaps as an alternative if pharmacological treatment is contraindicated.
The IASP defined TN as a sudden usually unilateral severe brief stabbing recurrent episode of pain in the distribution of one or more branches of the trigeminal nerve.  TN presents most commonly in the lower two branches of the trigeminal nerve. Very often it presents intraorally with triggers around the teeth, causing patients to undergo irreversible dental treatment unnecessarily. TN is often found to be misdiagnosed or over diagnosed as TMD especially if the TMD is unilateral. Having varied presentation, TN has been reported to present with considerable amount of less intense burning or dull pain after the main sharp attack of pain for more than 50% of the time. These have variously been labeled as type 2 or TN with concomitant pain. As an initial approach the symptomatic causes of TN need to be excluded e. g., tumors, often benign, multiple sclerosis and A-V malformations. Imaging and qualitative sensory testing are a part of routine work-up undertaken.
Antiepileptic medications are the drugs of choice for the management of TN. Carbamazepine, oxcarbazepine, gabapentin with second line drugs being lamotrigine and baclofen are used. If patients develop significant side effects or have poor pain control, then neurosurgical options such as microvascular decompression need to be considered. Microvascular decompression is the only non-destructive surgical procedure giving the longest pain-free interval 70% pain free at 10 years. For patients unsuitable for this procedure, ablative procedures include radiofrequency thermocoagulation glycerol rhizotomy, balloon compression or Gamma knife which gives 50% pain relief for four years but patients risk sensory changes which impact on quality of life. 
Glossopharyngeal neuralgia is a rare condition associated with pain in the area supplied by the glossopharyngeal nerve. Painful sites may include the nasopharynx, posterior part of the tongue, throat, tonsil, larynx and ear with activities like talking, coughing, chewing and swallowing being particular trigger factors. Due to the proximity of the vagal sensory nerves, glossopharyngeal neuralgia often coincides with a cardiac dysrhythmia such as bradycardia, asystole and syncope.
Diagnosis may be confirmed by blocking the tonsillar and pharyngeal region with topical or local anesthetics. Imaging with a CT scan of the head and a brain MRI should be conducted to rule out pathology related to the nerve compression and possible oropharyngeal carcinoma. Pharmacologic treatment of glossopharyngeal neuralgia is similar to that for TN and may include the use of antiepileptic medications. If medication management fails, then surgical procedures may be considered, such as a microvascular decompression to remove pressure from the glossopharyngeal nerve, radiofrequency thermocoagulation, gamma knife radiosurgery or rhizotomy. 
Peripheral trigeminal neuropathy
Peripheral neuropathic pain can arise as a result of a traumatic nerve injury resulting in chronic aching, continuous burning-like pain at the site of the injury. The basic etiology behind this condition can be attributed to a clear history of nerve injury ranging from a dental extraction, root canal filling, local anesthetic, implants to facial trauma in some instances. Thus the conditions are also referred as post-traumatic trigeminal neuropathy. Pain is often described as burning, stabbing; however, patients with definite nerve injury report a feeling of pins and needles, fizzing and swollen sensations. Pain in some circumstances is spontaneous while in others induced. When a nerve injury occurs, the transected nerve will sometimes attempt to restore itself through axonal sprouting, resulting in a traumatic neuroma. Clinical examinations often detect some sensory changes with somatosensory testing revealing evidence of hypoaesthesia or allodynia, most imaging is negative. Evaluation of peripheral nerve injuries through both subjective (history, questionnaires and examination) and objective (quantitative sensory testing and imaging) measures have been proposed. 
Diagnostic blocking of the painful site with topical anesthetic first (e. g., benzocaine) followed by a somatic block with local anesthetic (e. g., lidocaine injection) is recommended. If either of these blocks reduce or alleviate the pain, then topical creams or ointments may be utilized to treat the pain. Capsaicin is a common locally acting pharmacologic agent that can be utilized in cream or gel form applied with the neurosensory stent. Pharmaceuticals can produce a topical base containing combination of medications like analgesics/sedatives such as ketamine, NSAIDs such as diclofenac, anticonvulsant drugs such as gabapentin and carbamazepine, and TCA medications such as nortriptyline and amitriptyline. 
Centralized trigeminal neuropathy
A continuous, aching and burning pain with evidence of hyperalgesia and allodynia is described often due to central neural changes caused by prolonged stimulation of sensory nociceptors. Centrally acting systemic medications are used as major treatment approaches. Antiepileptic drugs, such as gabapentin and valproic acid, in combination with TCAs such as amitriptyline, may alleviate pain. ,
Atypical odontalgia [AO]
AO, a centralized trigeminal neuropathy localized in the dentoalveolar tissues, usually felt as a dull, throbbing, continuous, circulating pain which is often provoked by light touch. There may or may not exist a prior history of dental treatment. It is frequently misdiagnosed, leading to unnecessary dental treatments in attempts to relieve the pain. ,
The pharmacological management includes topical and systemic medications.  If the pain is localized to a peripheral origin with the diagnostic block suggesting an ambiguous response but a decrease in pain, a topical medication can be used with a neurosensory stent as an accession. Systemic approaches of management include use of TCAs, calcium channel blockers (pregabalin and gabapentin), sodium channel blockers (carbamazepine) and antiepileptics such as topiramate. A multidisciplinary approach stands necessary, which should include OFP specialists and neurologists in addition to psychiatric and psychological evaluations in order to identify comorbidities with depression and anxiety. , However it is important to avoid more surgical interventions.
Facial migraine/Neurovascular OFP
In facial migraine, however, the pain is usually localized in the lower part of the face. Migraine localized in the area of the maxillary branch distribution (V2) has also been reported. V2 gives rise to the nervus meningeus medius, which innervates the dura mater of the anterior floor of the middle fossa, thus explicating the localization of the pain in the maxillary area. Migraine symptomatology localized on the V3 territory has been reported too. 
Patient education forms an important part of management approach. When the pain is localized in the lower half of the face and/or in a tooth/teeth area (facial migraine), the patient should be assured that, even though the experienced pain may be severe and throbbing, it is not a toothache or related dental problem. Any trigger factors starting the migraine attack must be identified as an initial strategy.
Other non-pharmacological methods proving useful for facial migraine are biofeedback, relaxation techniques, hypnosis and psychological therapies. Abortive medications are the first line of treatment for the acute treatment of migraine. The use of NSAIDs, such as naproxen sodium and ibuprofen, has been shown to be probably effective in alleviating a headache attack.
Ergotamine derivatives, such as dihydroergotamine (DHE), a 5-HT1B and 5-HT1D agonist, have been used for years for the treatment of moderate to severe migraine; however, Serotonin 5-HT1B/1D receptor agonists i. e., triptans, because of their better tolerability and pharmacological specificity, have replaced ergotamine derivatives in the majority of cases. However, DHE, available in intranasal and injectable preparations, is useful for patients who typically do not respond to triptans. Combination preparations, such as sumatriptan with naproxen sodium, have shown additive effects in improving pain relief and migraine-associated symptoms. Recent developments include the use of CGRP receptor antagonists such as oral telcagepant  and 5-HT1F receptor agonist, lasmiditan,  as abortive agents in the treatment of acute migraine.
Persistent Idiopathic facial pain/Atypical facial pain [AFP]
Unlike others, this is a continuous pain which does not follow a neurological distribution. The pain often gradually becomes more diffuse and involves a larger area of the head and neck being often described as nagging and dull possessing sharp exacerbations. Neurophysiological testing has shown abnormalities similar to trigeminal neuropathic pain. Epidemiological studies and psychiatric judgments confer psychological factors to play a major role in this condition.
Psychosocial interventions include cognitive behavior therapy and biofeedback. Pharmacotherapeutic management includes a combination of antidepressants, analgesics, centrally acting muscle relaxants and anticonvulsant drugs.  Though surgery is not an appropriate for treatment for AFP, the frequent failure medical treatment to relieve pain has sometimes lead surgeons to attempt surgical treatments giving a temporary remission from pain. Descriptions of procedures such as removal of a portion of the affected branch of the trigeminal nerve, or direct injections of a caustic substance (e. g. phenol, glycerol, alcohol) into the nerve have been reported.
Giant cell arteritis
Principally occurring in the temple region jaw movement, this condition can induce more widespread pain and the tongue can be affected to such an extent that it appears cyanosed. Management approaches include initial erythrocyte sedimentation rate and C reactive protein test for any patients over 50 years. Temporal artery biopsy, ultrasonography and MRI scanning are also used as diagnostic tools.  Systematic steroids need to be commenced promptly to prevent blindness and other systemic effects
There is strong evidence to show that chronic OFP is associated with psychological factors , and co-occurs with other medically unexplained symptoms.  Evidence from randomized controlled trials ,, that early biopsychological interventions like cognitive behavioral therapy (CBT) and biofeedback mechanisms can improve outcome in patients with chronic OFP conditions like temporomandibular pain. Early intervention with psychosocial therapies such as CBT should be a priority for investigation as it has the potential to target negative thoughts, behaviors and/or feelings that may exacerbate pain symptoms through a vicious cycle. 
| Conclusion|| |
A multidisciplinary approach is ideal in the management of OFP disorders. The dental profession has struggled since decades to develop a systematic approach to nomenclature, diagnosis, treatment, and clinical research through numerous conferences, workshops and attempts at consensus. However despite these efforts, there is still no generally accepted professional agreement on the etiology and natural history of chronic OFP, the role of occlusion, treatment needs, and the effectiveness, safety and indications for most current practices.  OFP management can be challenging and the clinician should be well-aware of the different etiologies and characteristics of the diverse disorders of the orofacial region. Moreover, knowing increase concern IASP had announced the 2013-2014 global year against OFP and they promotes a yearlong initiative to raise international awareness of pain. 
There is a general desire by OFP patients to be understood, their pain to be acknowledged as real and to feel cared for as life has become hopeless and trust in the medical profession has been lost. Restoration of this faith with proper treatment approaches and further research advancements in OFP research can give this issue a new purview.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Alencar F. Chronic orofacial pain, central sensitization and sleep- is there a link? Dentistry 2013;3:2.
Zakrzewska JM. Multi-dimensionality of chronic pain of the oral cavity and face. J Headache Pain 2013;14:37.
Okeson JP. Bell′s Orofacial Pains. The Clinical Management of Orofacial Pain. 6 th
ed. Carol Stream, IL: Quintessence Publishing Co, Inc.; 2005.
Okeson JP. The Classification of orofacial pains. Oral Maxillofac Surg Clin North Am 2008;20:133-44.
Romero-Reyes M, Uyanik JM. Orofacial pain management: Current perspectives. J Pain Res 2014;7:99-115.
Takemura M, Sugiyo S, Moritani M, Kobayashi M, Yonehara N. Mechanisms of orofacial pain control in the central nervous system. Arch Histol Cytol 2006;69:79-100.
Nixdorf DR, Drangsholt MT, Ettlin DA, Gaul C, de LR, Svensson P, et al
. Classifying orofacial pains: A new proposal of taxonomy based on ontology. J Oral Rehabil 2012;39: 161-9.
Zakrzewska JM, Forssell H, Glenny AM. Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev 2005;1:CD002779.
McNeill C. Temporomandibular Disorders: Guidelines for Classification, Assesment, and Management. 2 nd
ed. Chicago, IL: Quintessence Publishing Co, Inc; 1993, p. 11-18.
Ohrbach R, Fillingim RB, Mulkey F, Gonzalez Y, Gordon S, Gremillion H, et al
. Clinical findings and pain symptoms as potential risk factors for chronic TMD: Descriptive data and empirically identified domains from the OPPERA case - control study. J Pain 2011;12:T27-45.
de Leeuw R. Temporomandibular Disorders. In: de Leeuw R, editor. Orofacial Pain Guidelines for Assesment, Diagnosis and Management. 4 th
ed. Hanover Park, IL: Quintessence Publishing Co, Inc; 2008. p. 158-76.
Clark GT, Seligman DA, Solberg WK, Pullinger AG. Guidelines for the examination and diagnosis of temporomandibular disorders. J Craniomandib Disord 1989;3:7-14.
Bezuur JN, Habets LL, Jimenez Lopez V, Naeije M, Hansson TL. The recognition of craniomandibular disorders - A comparison between clinical and radiographic findings in eighty-nine subjects. J Oral Rehabil 1988;15:215-21.
Randolph CS, Greene CS, Moretti R, Forbes D, Perry HT. Conservative management of temporomandibular disorders: A posttreatment comparison between patients from a university clinic and from private practice. Am J Orthod Dentofacial Orthop 1990;98:77-82.
Carlson CR, Okeson JP, Falace DA, Nitz AJ, Anderson D. Stretch-based relaxation and the reduction of EMG activity among masticatory muscle pain patients. J Craniomandib Disord 1991;5:205-12.
Gangarosa L, Mahan PE. Pharmacologic management of TMD-MPDS. Ear Nose Throat J 1982;61:670-8.
Wenneberg B, Kopp S, Gröndahl HG. Long-term effect of intra-articular injections of a glucocorticosteroid into the TMJ: A clinical and radiographic 8-year follow-up. J Craniomandib Disord 1991;5:11-8.
Song PC, Schwartz J, Blitzer A. The emerging role of botulinum toxin in the treatment of temporomandibular disorders. Oral Dis 2007;13:253-60.
Kreiner M, Betancor E, Clark GT. Occlusal stabilization appliances. Evidence of their efficacy. J Am Dent Assoc 2001; 132:770-7.
Dimitroulis G, Dolwick MF, Martinez A. Temporomandibular joint arthrocentesis and lavage for the treatment of closed lock: A follow-up study. Br J Oral Maxillofac Surg 1995;33:23-6.
Blaustein D, Heffez L. Diagnostic arthroscopy of the temporomandibular joint. Part II. Arthroscopic findings of arthrographically diagnosed disk displacements. Oral Surg Oral Med Oral Pathol 1988;65:135-41.
Merskey H, Bogduk N. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. International Association for the Study of Pain, Task Force on Taxonomy. 2 nd
ed. Seattle: IASP Press; 1994. p. 1-122.
Obermann M. Treatment options in trigeminal neuralgia. Ther Adv Neurol Disord 2010;3:107-15.
Meyer RA, Bagheri SC. Clinical evaluation of peripheral trigeminal nerve injuries. Atlas Oral Maxillofac Surg Clin North Am 2011;19:15-33.
Zakrzewska JM. Medical management of trigeminal neuropathic pains. Expert Opin Pharmacother 2010;11:1239-54.
Baad-Hansen L. Atypical odontalgia - Pathophysiology and clinical management. J Oral Rehabil 2008;35:1-11.
Patel SB, Boros AL, Kumar SK. Atypical odontalgia - An update. J Calif Dent Assoc 2012;40:739-47.
Daudia AT, Jones NS. Facial migraine in a rhinological setting. Clin Otolaryngol Allied Sci 2002;27:521-5.
Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, et al
. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: A randomised, placebo-controlled, parallel-treatment trial. Lancet 2008;372:2115-23.
Färkkilä M, Diener HC, Géraud G, Láinez M, Schoenen J, Harner N, et al
., COL MIG-202 study group. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: A phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol 2012;11:405-13.
List T, Axelsson S, Leijon G. Pharmacologic interventions in the treatment of temporomandibular disorders, atypical facial pain, and burning mouth syndrome. A qualitative systematic review. J Orofac Pain 2003;17:301-10.
Meisner RJ, Labropoulos N, Gasparis AP, Tassiopoulos AK. How to diagnose giant cell arteritis. Int Angiol 2011;30:58-63.
Aggarwal VR, McBeth J, Zakrzewska JM, Lunt M, Macfarlane GJ. The epidemiology of chronic syndromes that are frequently unexplained: Do they have common associated factors? Int J Epidemiol 2006;35:468-76.
Macfarlane TV, Blinkhorn AS, Davies RM, Ryan P, Worthington HV, Macfarlane GJ. Orofacial pain: Just another chronic pain? Results from a population-based survey. Pain 2002;99:453-8.
Stowell AW, Gatchel RJ, Wildenstein L. Cost-effectiveness of treatments for temporomandibular disorders: Biopsychosocial intervention versus treatment as usual. J Am Dent Assoc 2007;138:202-8.
Turner JA, Mancl L, Aaron LA. Brief cognitive-behavioral therapy for temporomandibular disorder pain: Effects on daily electronic outcome and process measures. Pain 2005;117:377-87.
Turner JA, Mancl L, Aaron LA. Short- and long term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: A randomized, controlled trial. Pain 2006;121:181-94.
Aggarwal VR, Lovell K, Peters S, Javidi H, Joughin A, Goldthorpe J. Psychosocial interventions for the management of chronic orofacial pain. Cochrane Database Syst Rev 2011:CD008456.
Management of temporomandibular disorders. National Institutes of Health Technology Assessment Conference Statement. J Am Dent Assoc 1996;127:1595-606.