Journal of

Oral Rehabilitation

Journal of Oral Rehabilitation 2014 41; 843--852

Review

Systematic review and recommendations for nonodontogenic toothache H. YATANI*, O. KOMIYAMA†, Y. MATSUKA‡, K. WAJIMA§, W. MURAOKA§, M . I K A W A ¶ , E . S A K A M O T O * * , A . D E L A A T † † & G . M . H E I R ‡ ‡ *Department of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, Osaka, †Department of Oral Function and Rehabilitation, Nihon University School of Dentistry at Matsudo, Matsudo, ‡Department of Stomatognathic Function and Occlusal Reconstruction, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, §Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo, ¶Orofacial Pain Clinic, Department of Oral Surgery, Shizuoka Municipal Shimizu Hospital, Shimizu, **Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan, Dentistry, University Hospitals, Leuven, Belgium and

††

Department of Oral Health Sciences, KU Leuven &

‡‡

Center for Temporomandibular Disorders and Orofacial Pain, Rutgers School of

Dental Medicine, The State University of New Jersey, Newark, NJ, USA

Nonodontogenic toothache is a painful condition that occurs in the absence of a clinically evident cause in the teeth or periodontal tissues. The purpose of this review is to improve the accuracy of diagnosis and the quality of dental treatment regarding nonodontogenic toothache. Electronic databases were searched to gather scientific evidence regarding related primary disorders and the management of nonodontogenic toothache. We evaluated the level of available evidence in scientific literature. There are a number of possible causes of nonodontogenic toothache and they should be treated. Nonodontogenic toothache can be categorised into eight groups according to primary disorders as SUMMARY

Background Non odontogenic toothache, as its name suggests, is a painful condition that occurs in the absence of any clinically evident cause in the teeth or periodontal tissues (1–4). Generally, 88% of patients with toothache-like pain visit a dental office; 3% of these patients have nonodontogenic toothache, and 9% have a mixed condition of odontogenic and nonodontogenic toothache. While the fact that nonodontogenic toothache is not rare has gained recognition (5), © 2014 John Wiley & Sons Ltd

follows: 1) myofascial pain referred to tooth/ teeth, 2) neuropathic toothache, 3) idiopathic toothache, 4) neurovascular toothache, 5) sinus pain referred to tooth/teeth, 6) cardiac pain referred to tooth/teeth, 7) psychogenic toothache or toothache of psychosocial origin and 8) toothache caused by various other disorders. We concluded that unnecessary dental treatment should be avoided. KEYWORDS: toothache, myofascial pain syndromes, neuralgia, myofascial pain syndromes, cerebrovascular disorders, cardiovascular diseases Accepted for publication 13 June 2014

general dentists and specialists may not be familiar with diagnostic criteria or management of nonodontogenic toothache (3, 5). Toothaches are frequently encountered in regular dental practice, and the diagnosis and treatment of primary toothache are not difficult; however, nonodontogenic toothache is not routinely studied. The current approach to nonodontogenic toothache often involves ineffective or irreversible dental procedures such as pulpectomy and/or tooth extraction (3, 5). As nonodontogenic toothache is a condition with doi: 10.1111/joor.12208

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H . Y A T A N I et al. multiple pathophysiological causes (1, 6–13), some patients may suffer from long-lasting pain of unknown origin after undergoing dental treatment. Irreversible dental treatment procedures must therefore be performed with caution in patients with toothache in the absence of clinically evident causes. The purpose of this review is to improve the accuracy of diagnosis and the quality of dental treatment for nonodontogenic toothache.

Each publication was initially assessed for relevance by two authors (YM, WM) using the information presented in the abstract. When an abstract was not available or failed to provide sufficient information, a reprint of the full paper was obtained. When papers or abstracts reported different stages of clinical trials, only the longer-term study was included in the review. All publications were then reviewed by seven authors (HY, OK, YM, KW, WM, MI and ES).

Methods The inclusion and exclusion criteria were first established for selecting papers from the available literature. The inclusion criteria consisted of English written clinical studies: systematic reviews, randomised controlled trials (RCTs), controlled clinical trials (CCTs) or case series in which diagnosis and treatment of nonodontogenic toothache were described. Treatment guidelines and systematic reviews for the diagnosis and treatment of a primary condition or diseases underlying nonodontogenic toothache (e.g. trigeminal neuralgia) were also included. Furthermore, case reports describing ‘Toothache caused by other various conditions or diseases’ were considered, because these conditions and diseases are rare. Studies without human subjects or articles written based on authors’ opinion were excluded. Both electronic and manual searches were undertaken to identify all clinically relevant studies written in English. The electronic search was conducted by two authors (OK, YM) using PubMed (Medline) on 30 October 2013 with the following retrieval style: non-odontogenic toothache OR nonodontogenic toothache OR atypical odontalgia OR toothache non dental OR (toothache AND neuralgia) OR [toothache AND (headache OR vascular OR neurovascular OR neurovascular orofacial pain)] OR [toothache AND (myofascial pain OR muscle pain OR myalgia OR musculoskeletal orofacial pain)] OR (toothache AND cardiac) OR (toothache AND neuropathic OR neuropathic orofacial pain) OR (toothache AND maxillary sinus) OR (toothache AND nasal mucosa) OR [toothache AND (psychogenic OR psychological)].’ A total of 891 studies were found. The reference lists of all the relevant studies, existing reviews and personal reprint collections of the authors were screened for additional relevant publications.

Results Many variable primary conditions or diseases cause nonodontogenic toothache (14–17), and there are some reports illustrating that pulpectomy (5) or tooth extraction (18) failed to relieve pain. As in most cases of idiopathic toothache, the pain increases following tooth extraction, spreading to adjacent teeth and continuing to the residual alveolar ridge, it is important to avoid pulpectomy or tooth extraction (5, 18). In 100 nonodontogenic oro facial pain patients referred to oro facial pain specialists, 44% had received tooth extraction or root canal treatment prior to referral (18). Understanding the primary problem underlying nonodontogenic toothache helps to identify the pathophysiology and is important for achieving a diagnosis and selecting a treatment plan. Nonodontogenic toothache may arise from a primary condition or from multifactorial aetiologies. Following the literature search, nonodontogenic toothache was categorised into eight groups according to primary disorders as follows: 1) myofascial pain referred to tooth/teeth, 2) neuropathic toothache, 3) idiopathic toothache, 4) neurovascular toothache, 5) sinus pain referred to tooth/teeth, 6) cardiac pain referred to tooth/teeth, 7) psychogenic toothache or toothache of psychosocial origin and 8) toothache caused by various other disorders (Table 1). Nonodontogenic toothache is a heterotopic pain. It consists of projected nerve pain which is felt throughout the peripheral distribution of the affected nerve (trigeminal neuralgia, cluster headache, post herpetic neuralgia etc.) or referred pain as a result of convergence and central sensitisation (myofascial pain referred to tooth/teeth, toothache, sinus pain referred to tooth/teeth, cardiac pain referred to tooth/teeth, etc.) (19). © 2014 John Wiley & Sons Ltd

© 2014 John Wiley & Sons Ltd

Idiopathic toothache

Continuous

Neuropathic toothache Episodic

Myofascial pain referred to tooth/ teeth

Cause of nonodontogenic toothache

Continuous pain in the teeth and/or periodontal tissues without objective pathophysiological or radiological findings at the site of pain, and with an unknown aetiology that lasts over 4 or 6 months

Paroxysms are provoked by relatively innocuous peripheral stimulation of a ‘trigger zone’ at intra-oral or extra oral sites such as the buccal mucosa above the molars, the lips, chin, nares and nasolabial fold. Pain is described as excruciating, electric-like and brief Continuous persistent pain (toothache-like) and associated symptoms Paraesthesia may be reported

Dull, aching and diffuse. Worsened by mastication, head and neck movements

Clinical features

The most frequent somatosensory abnormalities were somatosensory gain with regard to painful mechanical and cold stimuli and somatosensory loss with regard to cold detection and mechanical detection

Continuous neuropathic pain may be accompanied by sensory abnormalities such as hypersensitivity and/or allodynia.

Local anaesthesia with topical anaesthetic administered at the trigger zone intra-orally reduces the episodes of paroxysmal pain.

Provocation of myofascial trigger points and reproduction of referral patterns. Diagnostic injection eliminates pain.

Diagnostic test (After ruling out primary dental pathology)

Neuropathic pain, such as reported during the acute phase of a herpes zoster infection responds to valacyclovir hydrochloride, acyclovir, vidarabine, etc. First-line drugs for other continuous painful conditions include application of topical anaesthetics and the oral administration of TCAs or anticonvulsants Second-line drugs: non opioids or SNRI TCAs SDA antipsychotic drugs Topical treatment

Carbamazepine is the first choice, oxcarbazepine as the second choice and baclofen and lamotrigine as third choices

Behaviour modification Physical therapy NSAIDs Muscle relaxants TCAs

Treatment

Table 1. Representative causes of nonodontogenic toothache: clinical features, diagnostic test and treatment summary of each entity

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Psychogenic toothache or toothache of psychosocial origin

Cardiac pain referred to tooth/teeth

Sinus pain referred to tooth/teeth

Neurovascular toothache

Cause of nonodontogenic toothache

Table 1. (continued)

An inconsistent site of pain in the anatomical innervation area, bilateral symptoms, continuous and persistent pain

Pain occurs in the maxillary molar teeth induced by cold stimulation or mastication, and dysesthesia arises with tooth clenching ‘Tight’ and ‘burning’ Aggravated by exercise, improvement with rest, bilateral symptoms

Administered in accordance with the ICHD, and affected patients are referred to a neurologist, neurosurgeon or headache clinic. Pharmacologic therapy for migraines normally includes acetaminophen and NSAIDs. Triptans are used for the acute phase, and topiramate, valproic acid or amitriptyline as prophylactic treatment. Oxygen inhalation, triptans and dihydroergotamine were used for abortive therapy; verapamil, corticosteroids (short term), lithium, divalproex sodium, and topiramate were used for prophylactic therapy

Treatment

Paroxysmal hemicrania had a 100% response to indomethacin. Topiramate appears to be promising. Sinus toothache patients are referred to an Computerised tomography (CT) and otorhinolaryngologist histopathological examination showing Decongestants may be helpful. sinusitis or malignant fibrous histiocytoma Echocardiogram Refer to the cardiologist. Reduction of pain is observed following the Treatment includes anti-angina drugs administration of sublingual tablets of (beta-adrenoreceptor blockers, nitric acid, glyceryl trinitrate etc.) and antithrombotic drugs. Referral to a neuropsychiatrist, mental health professional or liaison treatment specialist. Treatment may include pharmacological therapy (antidepressant or antipsychotic drugs, etc.)

Dysautonomic accompaniments of cluster headache include lacrimation, rhinorrhea, scleral injection, pupillary miosis, as seen in Horner’s syndrome. There are no signs or symptoms between paroxysms, although neurovascular toothache may be induced by histamines and/or alcohol Acute, episodic periorbital and maxillary pain associated with dysautonomic features

TACs (trigeminal autonomic cephalalgia): Cluster headaches: Episodic, intense periorbital and maxillary pain lasting 15 to 180 min(82)

TACs: chronic paroxysmal hemicranias (CPH)

Migraines: May be accompanied by nausea, vomiting, photophobia, phonophobia, etc.

Diagnostic test (After ruling out primary dental pathology)

Migraine: Spontaneous, throbbing maxillary pain Made worse by physical activity Attacks last 4–72 h

Clinical features

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SYSTEMATIC REVIEW FOR NONODONTOGENIC TOOTHACHE

Myofascial pain referred to tooth/teeth Myofascial pain of the masticatory muscles is a frequently observed primary disorder associated with nonodontogenic toothache and symptoms including spontaneous and continuous dull pain (20). It was reported that 11% of myofascial pain patients complain of nonodontogenic toothache, and the masseter muscle often appears as the causal muscle (20). A significant number (49
6–85%) of cases of myofascial pain of the head and neck muscles involves nonodontogenic toothache induced by referred pain (20). A diagnosis of nonodontogenic toothache caused by myofascial pain can be effectively made based on the fact that five seconds palpation of the trigger points of the involved muscle increases the pain (21). The guidelines of the American Academy of Orofacial Pain (AAOP) (19) indicate that trigger point injection is useful for diagnostic decision making as well as for treatment. There are several scientifically verified papers regarding the reproducibility of sites of referred pain originating from trigger points (22, 23). Treatment. As toothache is caused by myofascial problems, behavioural modification (soft food diet, resting the jaw, self-massage, hot packs, etc.) is beneficial (19). Physical therapy is effective for treating toothache and includes the following treatments: stretching exercises, massage, thermotherapy and posture correction. Muscle relaxants can be used for pain relief (19), but their use should be limited to a few weeks (19). Pharmacologic therapies that demonstrated efficacy for myofascial pain causing nonodontogenic toothache involved ibuprofen and low-dose amitriptyline (19). There are only a few reliable studies that sufficiently support the efficacy of occlusal splint therapy in treating myofascial pain (24–27). Acupuncture has a statistically significant effect on temporomandibular disorders compared with a placebo (28), but the actual effect is controversial (29, 30). Neuropathic toothache Episodic neuropathic toothache Trigeminal neuralgia (TN) is a disorder associated with episodic neuropathic toothache (17, 31). The paroxysm of trigeminal neuralgia is provoked by relatively innocuous peripheral stimulation of a ‘trigger zone’ at intra-oral or extra-oral sites. TN must be differentiated © 2014 John Wiley & Sons Ltd

from pulpitis and local anaesthesia with 8% xylocaine spray administered at the trigger zone intra-orally reduces the episodes of paroxysmal pain (31). The absence of dental pathological findings should be confirmed using radiographic and clinical examinations (e.g. percussion pain of the tooth (31). The pathophysiology of TN is categorised as classical or secondary. In cases of vascular compression of trigeminal nerve root, demyelination may occur resulting in classical trigeminal neuralgia. Tumours or other demyelinating disorders such as multiple sclerosis or other autoimmune diseases may be the cause of symptomatic secondary TN (32). Treatment. According to the guidelines developed by the American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS), there is strong evidence to support the use of carbamazepine as a first-line drug for trigeminal neuralgia (33). These societies recommend oxcarbazepine as the second choice and baclofen and lamotrigine as third choices (34). Toothache may disappear concurrently with improvements in paroxysmal neuralgia; however, it may be difficult to make a diagnosis in cases of comorbidity with odontogenic pathology (32). The surgical procedures include microvascular decompression, radiofrequency thermocoagulation and stereotactic radiosurgery (gamma knife surgery) for classical TN (35). Continuous neuropathic toothache Herpes zoster (HZ) of the face may also be associated with toothache, and pulpitis-like pain suddenly appears in healthy teeth and becomes intense within a few days. Painful posttraumatic trigeminal neuropathy (PTTN) developing as a result of nerve injury that occurs during dental treatment is also a cause of persistent neuropathic toothache (36). Treatment. Pharmacological therapy for continuous neuropathic pain should be administered according to the guidelines developed by the National Institute for Health and Clinical Excellence (NICE) (37), the IASP (38) and the EFNS (39). Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect (40). Patches with

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H . Y A T A N I et al. a local anaesthetic have also been shown to provide relief when applied to affected areas (41).

Other topical treatments for chronic neuropathic pain have been reported (49, 59, 60).

Idiopathic toothache

Neurovascular toothache

There are no multidisciplinary studies on idiopathic toothache (i.e., persistent dentoalveolar pain: PDAP) as the diagnostic criteria for the condition is unclear (42, 43). Some reports define idiopathic toothache as characterised by continuous pain in the teeth and/or periodontal tissues without objective pathophysiological or radiological findings at the site of pain and with an unknown aetiology that lasts over 4 or 6 months (44, 45). Neuropathic and idiopathic toothaches are closer to each other, as studies from the last decade indicate that patients clinically diagnosed with atypical odontalgia (AO) may in fact suffer from ‘definite’ or ‘probable’ PTTN, if somatosensory disturbances can be demonstrated and if other confirmatory tests can be applied (46–48). The new IHS classification (32) refers to this entity as PIFP (persistent idiopathic facial pain) (49) and classifies it as a painful trigeminal neuropathy (47), while the term ‘atypical odontalgia’, used in this paper as a historical reference, is no longer in common use. Around 85% of patients with atypical odontalgia exhibit abnormal qualitative somatosensory responses (50). The most frequent somatosensory abnormalities in AO patients were somatosensory gain with regard to painful mechanical and cold stimuli and somatosensory loss with regard to cold detection and mechanical detection (46). As mentioned, quantitative sensory testing (QST) is useful in diagnostic decision making of atypical odontalgia in each patient (51–53). Atypical odontalgia patients complain of increased pain intensity following the application of topical capsaicin cream (54) and have diminished blink reflex R2 waves in comparison with normal subjects (55).

The relationship between toothache and neurovascular headaches such as migraines (16), cluster headaches and other trigeminal autonomic cephalalgias (TACs) cannot be denied, as patients with neurovascular headaches commonly visit dental clinics with the chief complaint of toothache (16, 61). Migraine without aura, which arises in the mid face, has a throbbing and persistent quality similar to toothache. Van Vliet et al. (62) showed that 34% of 1163 cluster headache patients visited a dental clinic. Regarding cluster headaches, continuous intense pain occurs in the maxillary molar region for 15–180 min and then suddenly disappears (62). It is important to examine the available diagnostic criteria for various eadaches following the International Classification of Headache Disorders (ICHD) (32).

Treatment. The efficacy of tricyclic antidepressants was shown to be 60–75% (56) for idiopathic toothache with most common reports using amitriptyline. Tricyclic antidepressants are considered to have a high efficacy; however, only case series or case–controlled studies were available, and the evidence level is not high (57, 58). Anticonvulsants are frequently used, as a considerable proportion of these patients may have neuropathic mechanisms underlying their pain (49).

Treatment. Treatment for neurovascular toothache following migraine, cluster headaches paroxysmal hemicranias and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is based on recommendations of the ICHD (32), and affected patients are referred to a neurologist, neurosurgeon or headache clinic (16). Pharmacologic therapy for migraines normally includes triptans, which are used in the acute phase as abortive therapy. Topiramate, valproic acid or amitriptyline are used for prophylactic treatment (19, 63). Regarding cluster headache, oxygen inhalation, triptans and dihydroergotamine were used for abortive therapy, while verapamil, corticosteroids (short term), lithium, divalproex sodium and topiramate were used for prophylactic therapy (64, 65). Sinus pain referred to tooth/teeth Sinus pain referred to tooth/teeth is due to referred pain from acute sinusitis. Toothache due to acute sinusitis frequently occurs in the maxillary pre molar and molar regions, but it is rare that chronic sinusitis is accompanied by toothache; it typically induces nasal congestion and dull headaches (66). Pain occurs in the maxillary molar teeth induced by cold stimulation or mastication, and dysesthesia arises with tooth © 2014 John Wiley & Sons Ltd

SYSTEMATIC REVIEW FOR NONODONTOGENIC TOOTHACHE clenching. The pain increases when the patient bends over. Sinus pain referred to tooth/teeth is diagnosed using computed tomography (CT) and histopathological examination showing sinusitis or malignant fibrous histiocytoma (67). Treatment. The patients with toothache due to acute sinusitis should be referred to an otorhinolaryngologist for treatment of nonodontogenic sinusitis. Cardiac pain referred to tooth/teeth There are many reports regarding toothache caused by ischaemic heart diseases such as angina (68–71). Kreiner et al. reported that 71 (38%) of 186 ischaemic heart disease patients experienced facial pain during heart attacks with a significantly higher frequency in females. Eighty-five per cent (60/71) experienced chest and facial pain simultaneously, while 11 of 71 (15%) experienced facial pain only (72). Dentists need to be aware of the possibility of ischaemic heart disease in patients who visit the clinic with complaints of toothache only. Referred pain caused by ischaemic heart disease is described as ‘tight’ and ‘burning’ in contrast to the ‘throbbing’ and ‘tingling’ in odontogenic toothache. The common characteristic features of ischaemic heart disease (aggravation induced by exercise, improvement at rest, bilateral symptoms, etc.) should be considered in diagnostic decision making (73). An echocardiogram can be used to diagnose aortic dissection. Treatment. Patients with cardiac pain referred to tooth/teeth must be referred to the cardiologist or other internal medicine specialists for treatment of the primary disease. Treatment includes anti-angina drugs (beta-adrenoreceptor blockers, nitric acid, etc.) and antithrombotic drugs (antiplatelet drugs, anticoagulants, etc.). Psychogenic toothache or toothache of psychosocial origin Biopsychosocial factors affect pain, and chronic pain is closely related to psychosocial problems (74, 75), but there is no convincing evidence that psychological or emotional issues can induce pain. Pain descriptors are often diffuse, vague and difficult to localise. When the somatoform pain disorder is felt in the teeth, multiple © 2014 John Wiley & Sons Ltd

teeth are often involved. Pain may be sharp, stabbing, intense and sensitive to temperature changes, all of which are similar to pain symptoms of odontogenic origin. However, the pain is inconsistent with normal patterns of physiologic pain and presents without any identifiable pathologic cause. When accompanied by other psychiatric features such as hallucinations or delusions, there is a greater possibility that the pain is of psychogenic origin. Treatment. Patients with psychogenic toothache caused by mental disorders need to be referred to neuropsychiatrists or liaison treatment specialists and treated with pharmacological therapy (antidepressant or antipsychotic drugs, etc.). Given that psychogenic toothache is a somatoform disorder, dental treatment will not resolve symptoms of pain and may potentially elicit an unexpected or unusual response to therapy. Patients should be referred to a psychiatrist or psychologist for further management. We must mention that chronic pain can cause depression or somatisation as well (76). Toothache caused by other various conditions or diseases Life-threatening diseases such as metastasis in the oral and maxillofacial area and breast carcinoma have been reported as primary causes of toothache (77). Angioleiomyoma and methemoglobinemia may also be a primary disease of nonodontogenic toothache (78, 79). The most common cause for mental nerve neuropathy was dental treatment followed by malignant metastasis (80). Chemotherapy-induced toxicity injuries to the peripheral nerve might manifest as pulpitis-like toothache (81). One of seven patients with temporal arteritis complains of toothache and gingival pain (82). An erythrocyte sedimentation rate (ESR) >50 mm and the findings of a biopsy of the temporal artery are used to differentiate temporal arteritis (82). It is recommended that toothache caused by temporal arteritis be treated with steroid therapy by a rheumatologist or neurologist (82). Pain-like trigeminal neuralgia and numbness of the gingiva and buccal mucosa have been reported in cases of pontine infarction (83) or tumour (84). CT or MRI are used to confirm the primary diseases of adult T-cell lymphoma, jaw bone tumour, cervical disc herniation, cholesterol granuloma, brain tumour (meningioma),

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Conclusions This review outlines clinical practice guidelines for treating nonodontogenic toothache based on the available basic scientific knowledge and treatment systems and is addressed to all medical personnel involved in dental treatment. The literature was searched for information on nonodontogenic toothache and its related primary diseases. However, nonodontogenic toothache is a condition with multiple pathophysiological causes, and the process was difficult because high quality literature is still sparse. Further studies with appropriate evidence levels will be needed in the future.

Disclosure It is not necessary for ethical approval because this study is a systematic review. No source of fundings and no conflict of interests declared.

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