“Convergence” occurs when multiple presynaptic neurons signal input onto a single postsynaptic neuron. In referred pain, primary afferent fibers from various tissues, converge onto a single higher order neuron, resulting in pain felt at a distant site. A good example of this in medicine is the diversity of “felt pain” in chronic pelvic pain, where the patient describes the pain in a wide anatomic distribution, such as the genitalia, thighs, perianal region, and the abdomen. ^, Diverse pain referral patterns are observed in the orofacial region due to the phenomenon of convergence. A bidirectional pain referral is observed due to the convergence of spinal nerves C1 to C3, and the trigeminal nerve. This presentation may confuse the patient and the clinician and may lead to underdiagnosis, misdiagnosis, and resultant suboptimal pain management. ^, Pain of cardiac origin felt in the jaw and teeth is a result of trigeminocervicovagal convergence. The lack of knowledge about these mechanisms may eventually cause chronification of pain, leading to reduced quality of life and disability.

Myofascial pain refers to pain originating from muscles and fascia. It is one of the major causes of NOTA. ^, NOTA of myofascial origin is characterized by pain referring from a trigger point in the muscle to a tooth or teeth. Myofascial trigger point refers to a hyperirritable spot in the taut band of a skeletal muscle. Trigger points that are a part of a patient’s chief complaint and reproduce the known pain are known as active trigger points, whereas those that are incidentally found are referred to as latent trigger points. The source and site of pain are different.

The toothache of myofascial origin may mimic the pain of pulpitis, or present as tooth sensitivity. This leads to misdiagnosis, resulting in improper treatment or management of the same. ^,, Myofascially induced toothache may present as dull aching pain as opposed to pulsatile dental pain. Some of the diagnostic testing for the evaluation of the source of pain include diagnostic local anesthesia in an attempt to anesthetize the tooth (site of pain). The fact that this anesthesia does not relieve the toothache, combined with the reproduction of toothache from activation of a trigger point, guides to a proper diagnosis of myofascially induced toothache. Other succinct indicators of a myofascially induced odontalgia may include, but not limited to, muscle function increasing the intensity of the toothache, lack of abnormal clinical and radiographic dental findings, negative pulp testing, and reducing or relieving of toothache upon appropriate trigger point injection. ^,, An exemplification of these referral patterns are depicted in Fig. 2 and Table 1 . ^,,, Conversely, odontogenic infections may refer to soft tissues including muscles. Some of the management modalities for myofascially induced toothache are listed in Table 1 . ^,,

Myofascial pain referral pattern of temporalis muscle.

( Courtesy image by Dr. Tanvee Somaiya, BDS.)

Neurovascular headache disorders encompass neural and vascular pathophysiology, including migraines and trigeminal autonomic cephalalgias (TACs). These conditions typically present with pulsatile cephalalgia, allodynia, photophobia, phonophobia, nausea, and periorbital pain. The pain attacks may be accompanied by autonomic features. A variant of migraine specific to the face and teeth is called facial migraine (midface migraine). ^,,, Similarly, TACs present as unilateral facial pain, occasionally with dental pain. ^,, These may lead to a diagnostic ambiguity and unnecessary invasive dental procedures. In such cases, comprehensive clinical assessment and meticulous investigative protocols are essential. ^,,,

Trigeminal neuralgia (TN) is a chronic neuropathic pain condition with paroxysms of pain that can be triggered by innocuous stimuli in the trigger zone, presenting as toothaches. ^, TN has an incidence of 0.1% to 0.3%, affecting women more than men with a 2.5:1 ratio. ^, This may be reflected in the prevalence of NOTA secondary to TN. Consequently, the probability of maxillary and mandibular teeth being affected by NOTA secondary to TN may be high. NOTA due to neuralgias may manifest with paroxysmal, unremitting pain of more than 3 months duration in the involved tooth. Due to the diversity of the triggers for NOTA secondary to TN, including brushing of teeth, cold foods, chewing, pressing/touching the gums, cold breeze, and drinking beverages, the clinician may have difficulty in achieving an accurate diagnosis. Unfortunately, this may open up a gateway to largely unnecessary and extensive irreversible dental procedures in an attempt to achieve pain control in cases of NOTA. ^,, Consequently, it is not uncommon for a patient with chronic NOTA to present with complete or partial edentulous arches. ^,, Some patients may present with dull, aching tooth pain, or dentinal sensitivity without any obvious dental causes. This is characteristic of pre-TN, which may present as a diagnostic challenge for the treating dentist. An interdisciplinary management approach may involve medical or surgical interventions. ^,

Persistent posttraumatic trigeminal neuropathic pain may occur due to trauma to the trigeminal nerve fibers. Postendodontic pain has been reported in 2% to 15% of patients. ^,, Traumatic neuroma involves abnormal proliferation of a damaged nerve. Oral traumatic neuroma though rare, may present as NOTA, posing a diagnostic challenge. ^, This may lead to misdiagnosis and resultant unnecessary procedures/overtreatment. ^,, Patients may present with altered sensations.

Angina of cardiac origin may present as jaw or tooth aches due to convergence ( Fig. 3 ). Further, in the absence of chest pain, the most frequently reported orofacial pain sites of cardiac origin were the throat, teeth, ear, and temporomandibular regions. Once the orofacial source/dental source of pain is effectively ruled out, and cardiac origin is suspected, it is imperative to promptly refer the patient to emergency care for immediate evaluation and management.

Convergence in NOTA due to cardiac origin.

( Courtesy image by Dr. Ahana Ajayakumar, BDS.)

Lyme disease is a vector-borne disease affecting multiple systems. One of the presenting symptoms may be a toothache. A thorough travel history, clinical examination, and detailed blood investigations are cardinal in the diagnosis of Lyme disease, thus aiding in the diagnosis of NOTA in these patients. ^,, Additionally, dental pain incidences have been reported during coronavirus disease 2019 infections, ^,,, human immunodeficiency virus infections, herpes zoster infections, and chikungunya (oral mucosal pain and temporomandibular disorders [TMDs]).

Giant cell arteritis (GCA) is a vascular, inflammatory condition affecting the medium and large arteries. More commonly involved is the temporal artery. ^, Pain on chewing, toothaches, and gingival pain have been reported in GCA. ^,, NOTA due to GCA though uncommon, should be considered as one of the differential diagnoses if present with other clinical presentations. Monckeberg medial sclerosis is another entity that has been reported to cause facial pain in a similar manner. It must be noted that other similar vascular entities may present as NOTA and may need an interdisciplinary approach.

Conditions such as sickle cell disease (SCD), benign and malignant neoplasms, and demyelinating disorders (such as multiple sclerosis [MS]), among others may present as NOTAs. Vasoocclusive crises of SCD may result in symptomatic and asymptomatic pulpal necrosis in an otherwise healthy tooth, presenting as NOTA. ^, In patients with MS, NOTA may occur as a consequence of secondary TN. NOTA may be caused by conditions such as Burkitt’s lymphoma ^, and Wegener’s granulomatosis. In addition, genetic factors may contribute to NOTA as well.

Bisphosphonates are used in conditions such as osteoporosis, Paget’s disease, and malignancies. Bisphosphonates have also been shown to cause osteonecrosis of the jaws. ^,,,, Patients may present with symptoms such as jaw pain, numbness, and tooth mobility, among others. ^,, It is conceivable that during the course of this entity’s evolving, the patient may experience and may complain of a toothache. Consequently, these dental/oral manifestations may present as NOTAs. Neurotoxicity due to chemotherapeutic drugs has been shown to present as NOTAs. ^,, Clinical and radiographic examination, thorough medical history including medications, aid in the accurate diagnosis of the same. An interdisciplinary management approach is desired for these patients.

The anatomic features and the intricate relationship between the maxillary sinus and the maxillary teeth, combined with the commonality in the innervations, and neural convergence can contribute to NOTA. ^, Conditions affecting the maxillary sinus may also cause referred pain in the teeth. Approximately 9% to 11% of patients with maxillary sinus infection report toothache in the ipsilateral maxillary posterior teeth. The pathophysiology also involves the convergence of sensory afferent nerves of the sinuses and teeth. Nasal mucosal infections have also shown to refer pain in the maxillary teeth. An interesting concept that has gained momentum in the area of neuroscience of pain is called perineural inflammation, causing pain in the target organ innervated by the nerve. In a dental perspective, the symptoms may include tenderness to percussion on the maxillary posterior teeth, cold hypersensitivity with secondary hyperalgesia, and pain in the maxillary posterior region. Upon local anesthetic blocks, NOTA due to sinusitis may be equivocal. Imaging may show mucosal thickening or the presence of fluid in the maxillary sinus on the ipsilateral side versus the contralateral. Accurate differentiation between odontogenic toothache and NOTA from the maxillary sinusitis can be detected only by careful history taking, clinical examination, and radiographs.

The complex interaction between the sinonasal symptoms and NOTAs makes the diagnosis and management challenging. An interdisciplinary approach involves the otorhinolaryngologist, and radiologist, among others, for the evaluation of sinonasal symptoms. The specialist may then utilize imaging, culture and sensitivity tests, and succinct management modalities.

Central lesions such as benign and malignant tumors, and vascular malformations affecting the V to XII cranial nerves, can cause a variety of orofacial pain symptoms including NOTA. ^,,, Common symptoms may include tinnitus, hearing loss, and numbness; but in certain unusual cases, it may present as NOTA, pain on chewing, reduced muscle tonicity on the affected side, ipsilateral burning mouth, hyperalgesia, and paresthesia in the orofacial region. ^,, Malignancies with metastatic lesions either in the jaws or brain can cause NOTA. ^,, NOTA due to central lesions may go undiagnosed/misdiagnosed. Therefore, a thorough, diligent case workup and investigations are prudent for accurate diagnosis and to minimize suffering for the patient.

Various rare conditions presenting as NOTAs include, but not limited to, angioleiomyoma of the nasolabial groove, vertebral artery pseudoaneurysm, foreign body in the nasal cavity, and inflammatory myofibroblastic tumor of the nasal cavity and intranasal sinuses. Some cervical/neck conditions have also been shown to present as NOTAs. These include peritonsillar or parapharyngeal abscess, cervico-facial necrotizing fasciitis, calcified/calcifying stylohyoid ligament, and alcohol-induced vasospastic angina, among others.

Barodontalgia refers to toothache due to pressure/altitude changes. It may be observed in air travelers and divers and has higher prevalence in maxillary teeth. ^,,, It has also been observed in patients undergoing hyperbaric oxygen therapies, and while traveling back home after dental tourism appointments. Patients may present with toothaches after their flight travel, or activities such as scuba diving. Taking a proper travel history and clinical examination in such cases aids in accurate diagnosis. Regular dental checkups, addressing of required dental treatment, and following postprocedural instructions, help in the management of these patients. ^,

Toothaches of psychogenic origin are rare. Psychological factors have been shown to impact chronic pain. ^, Emotional or psychological factors, many a times, can affect pain perception, as opposed to inducing pain. Patients may complain of sensitivity: sharp, stabbing, or intense pain in multiple teeth without any obvious dental pathology that may otherwise explain the pain. These cases may present with delusions, hallucinations, or other psychiatric conditions, along with NOTA. ^, A thorough clinical examination and detailed history is cardinal for accurate diagnosis and prompt referral. Management of these patients involves referral to an orofacial pain specialist, along with a psychologist or psychiatrist, thus involving an interdisciplinary care. Succinct knowledge and understanding of such conditions help in minimizing underdiagnosis, misdiagnosis, and irreversible overtreatment of these patients. ^,, Psychogenic NOTAs pose a real diagnostic challenge due to its rare and complex presentation. When a psychogenic pain is suspected, before labeling it as such, every attempt should be exhausted to explore a somatic etiology of the pain. An astute clinician should evaluate the patient thoroughly to avoid any irreversible treatment in these conditions.

A summary of the etiology of NOTAs is given in Table 2 .