As with many conditions without clear physical or laboratory diagnosis, TN is sometimes misdiagnosed. A TN sufferer will sometimes seek the help of numerous clinicians before a firm diagnosis is made.

There is evidence that points towards the need to quickly treat and diagnose TN. It is thought that the longer a patient suffers from TN, the harder it may be to reverse the neural pathways associated with the pain.

The differential diagnosis includes temporomandibular disorder. Since triggering may be caused by movements of the tongue or facial muscles, TN must be differentiated from masticatory pain that has the clinical characteristics of deep somatic rather than neuropathic pain. Masticatory pain will not be arrested by a conventional mandibular local anesthetic block. One quick test a dentist might perform is a conventional inferior dental local anaesthetic block, if the pain is in this branch, as it will not arrest masticatory pain but will TN.

Trigeminal neuralgia is diagnosed via the result of neurological and physical test, as well as the individuals medical history.

Both forms of facial neuralgia are relatively rare, with an incidence recently estimated between 12 and 24 new cases per hundred thousand population per year.

ATN often goes undiagnosed or misdiagnosed for extended periods, leading to a great deal of unexplained pain and anxiety. A National Patient Survey conducted by the US Trigeminal Neuralgia Association in the late 1990s indicated that the average facial neuralgia patient may see six different physicians before receiving a first definitive diagnosis. The first practitioner to see facial neuralgia patients is often a dentist who may lack deep training in facial neurology. Thus ATN may be misdiagnosed as Tempormandibular Joint Disorder.

This disorder is regarded by many medical professionals to comprise the most severe form of chronic pain known in medical practice. In some patients, pain may be unresponsive even to opioid drugs at any dose level that leaves the patient conscious. The disorder has thus acquired the unfortunate and possibly inflammatory nickname, "the suicide disease".

Symptoms of ATN may overlap with a pain disorder occurring in teeth called atypical odontalgia (literal meaning "unusual tooth pain"), with aching, burning, or stabs of pain localized to one or more teeth and adjacent jaw. The pain may seem to shift from one tooth to the next, after root canals or extractions. In desperate efforts to alleviate pain, some patients undergo multiple (but unneeded) root canals or extractions, even in the absence of suggestive X-ray evidence of dental abscess.

ATN symptoms may also be similar to those of post-herpetic neuralgia, which causes nerve inflammation when the latent herpes zoster virus of a previous case of chicken pox re-emerges in shingles. Fortunately, post-herpetic neuralgia is generally treated with medications that are also the first medications tried for ATN, which reduces the negative impact of misdiagnosis.

The subject of atypical trigeminal neuralgia is considered problematic even among experts. The term atypical TN is broad and due to the complexity of the condition, there are considerable issues with defining the condition further. Some medical practitioners no longer make a distinction between facial neuralgia (a nominal condition of inflammation) versus facial neuropathy (direct physical damage to a nerve).

Due to the variability and imprecision of their pain symptoms, ATN or atypical odontalgia patients may be misdiagnosed with atypical facial pain (AFP) or "hypochondriasis", both of which are considered problematic by many practitioners. The term "atypical facial pain" is sometimes assigned to pain which crosses the mid-line of the face or otherwise does not conform to expected boundaries of nerve distributions or characteristics of validated medical entities. As such, AFP is seen to comprise a diagnosis by reduction.

As noted in material published by the [US] National Pain Foundation: "atypical facial pain is a confusing term and should never be used to describe patients with trigeminal neuralgia or trigeminal neuropathic pain. Strictly speaking, AFP is classified as a "somatiform pain disorder"; this is a psychological diagnosis that should be confirmed by a skilled pain psychologist. Patients with the diagnosis of AFP have no identifiable underlying physical cause for the pain. The pain is usually constant, described as aching or burning, and often affects both sides of the face (this is almost never the case in patients with trigeminal neuralgia). The pain frequently involves areas of the head, face, and neck that are outside the sensory territories that are supplied by the trigeminal nerve. It is important to correctly identify patients with AFP since the treatment for this is strictly medical. Surgical procedures are not indicated for atypical facial pain."

The term "hypochondriasis" is closely related to "somatoform pain disorder" and "conversion disorder" in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association. As of July 2011, this axis of the DSM-IV is undergoing major revision for the DSM-V, with introduction of a new designation "Complex Somatic Symptom Disorder". However, it remains to be demonstrated that any of these "disorders" can reliably be diagnosed as a medical entity with a discrete and reliable course of therapy.

It is possible that there are triggers or aggravating factors that patients need to learn to recognize to help manage their health. Bright lights, sounds, stress, and poor diet are examples of additional stimuli that can contribute to the condition. The pain can cause nausea, so beyond the obvious need to treat the pain, it is important to be sure to try to get adequate rest and nutrition.

Depression is frequently co-morbid with neuralgia and neuropathic pain of all sorts, as a result of the negative effects that pain has on one's life. Depression and chronic pain may interact, with chronic pain often predisposing patients to depression, and depression operating to sap energy, disrupt sleep and heighten sensitivity and the sense of suffering. Dealing with depression should thus be considered equally important as finding direct relief from the pain.

Treatment of people believed to have ATN or TN is usually begun with medication. The long-time first drug of choice for facial neuralgia has been carbamazepine, an anti-seizure agent. Due to the significant side-effects and hazards of this drug, others have recently come into common use as alternatives. These include oxcarbazepine, lamotrigine, and gabapentin. A positive patient response to one of these medications might be considered as supporting evidence for the diagnosis, which is otherwise made from medical history and pain presentation. There are no present medical tests to conclusively confirm TN or ATN.

If the anti-seizure drugs are found ineffective, one of the tricyclic antidepressant medications such as amitriptyline or nortriptyline, may be used. The tricyclic antidepressants are known to have dual action against both depression and neuropathic pain. Other drugs which may also be tried, either individually or in combination with an anti-seizure agent, include baclofen, pregabalin, anti-seizure drugs (to calm nerve endings), muscle relaxants, and opioid drugs such as oxycodone or an oxycodone/paracetamol combination.

For some people with ATN opioids may represent the only viable medical option which preserves quality of life and personal functioning. Although there is considerable controversy in public policy and practice in this branch of medicine, practice guidelines have long been available and published.

Lab Studies:

- No laboratory work is usually necessary.

- Results of cerebrospinal fluid evaluation are abnormal in 61%.

- Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%.

- These findings are not predictive of the clinical course of postherpetic neuralgia.

- Viral culture or immunofluorescence staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically.

- Antibodies to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out.

Imaging studies:

- Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients.

- At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia.

- Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain.

The ICHD-2 lists diagnostic criteria for "persistent idiopathic facial pain" (the term that replaces AFP in this classification):

There are presently no accepted medical tests which consistently discriminate between facial pain syndromes or differentiate Atypical Facial Pain from other syndromes. However, a normal Radiograph, CT, and MRI may help to exclude other pathology such as arterio-veinous malformation, tumor, temporomandibular joint disorder, or MS.

Research suggests that people with AFP are not helped greatly by health care professionals. One study reported that on average, individuals had consulted 7.5 different doctors. 91% had seen dentists, 80% physicians, 66% neurologists, 63% ear, nose and throat surgeons, 31% orthopedic and maxillofacial surgeons, 23% psychiatrists, 14% neurosurgeons and 6% ophalmologists and dermatologists. In this study, the individuals had been subjected to a wide variety of different treatments, from surgery, antidepressants, analgesics and physical therapies. None of the persons reported that surgery was beneficial, and in many cases the pain was worsened by surgery. The article sited as the source of this information was withdrawn from publication, saying the information was out of date and not meeting Cochrane methodological standards.

It has been suggested that the onset of chronic facial will likely be a life changing development for those affected.

Cluster headaches are often misdiagnosed, mismanaged, or undiagnosed for many years; they may be confused with migraine, "cluster-like" headache (or mimics), CH subtypes, other TACs ( trigeminal autonomic cephalalgias), or other types of primary or secondary headache syndrome. Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.

A detailed oral history aids practitioners in correct differential diagnosis, as there are no confirmatory tests for CH. A headache diary can be useful in tracking when and where pain occurs, how severe it is, and how long the pain lasts. A record of coping strategies used may help distinguish between headache type; data on frequency, severity and duration of headache attacks are a necessary tool for initial and correct differential diagnosis in headache conditions.

Correct diagnosis presents a challenge as the first CH attack may present where staff are not trained in the diagnosis of rare or complex chronic disease. Although experienced ER staff are sometimes trained to detect headache types, CH attacks themselves are not directly life-threatening, they are linked to an increased risk of suicide.

Individuals with CH typically experience diagnostic delay before correct diagnosis. People are often misdiagnosed due to reported neck, tooth, jaw, and sinus symptoms and may unnecessarily endure many years of referral to ear, nose and throat (ENT) specialists for investigation of sinuses; dentists for tooth assessment; chiropractors and manipulative therapists for treatment; or psychiatrists, psychologists and other medical disciplines before their headaches are correctly diagnosed. Under-recognition of CH by health care professionals is reflected in consistent findings in Europe and the United States that the average time to diagnosis is around seven years. Medical students receive little training in differential diagnoses and management of headaches.

Cluster headache may be misdiagnosed as migraine or sinusitis. Other types of headache are sometimes mistaken for, or may mimic closely, CH. Incorrect terms like "cluster migraine" confuse headache types, confound differential diagnosis and are often the cause of unnecessary diagnostic delay, ultimately delaying appropriate specialist treatment.

Headaches that may be confused with CH include:

- Chronic paroxysmal hemicrania (CPH) is a unilateral headache condition, without the male predominance usually seen in CH. Paroxysmal hemicrania may also be episodic but the episodes of pain seen in CPH are usually shorter than those seen with cluster headaches. CPH typically responds "absolutely" to treatment with the anti-inflammatory drug indomethacin where in most cases CH typically shows no positive indomethacin response, making "Indomethacin response" an important diagnostic tool for specialist practitioners seeking correct differential diagnosis between the conditions.

- Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a headache syndrome belonging to the group of TACs.

- Trigeminal neuralgia is a unilateral headache syndrome, or "cluster-like" headache.

A lumbar puncture is a procedure in which cerebral spinal fluid is removed from the spine with a needle. A lumbar puncture is necessary to look for infection or blood in the spinal fluid. A lumbar puncture can also evaluate the pressure in the spinal column, which can be useful for people with idiopathic intracranial hypertension (usually young, obese women who have increased intracranial pressure), or other causes of increased intracranial pressure. In most cases, a CT scan should be done first.

All people who present with red flags indicating a dangerous secondary headache should receive neuroimaging. The best form of neuroimaging for these headaches is controversial. Non-contrast computerized tomography (CT) scan is usually the first step in head imaging as it is readily available in Emergency Departments and hospitals and is cheaper than MRI. Non-contrast CT is best for identifying an acute head bleed. Magnetic Resonance Imaging (MRI) is best for brain tumors and problems in the posterior fossa, or back of the brain. MRI is more sensitive for identifying intracranial problems, however it can pick up brain abnormalities that are not relevant to the person's headaches.

The American College of Radiology recommends the following imaging tests for different specific situations:

Diagnostic criteria:

A. Pain paroxysms of intermittent occurrence, lasting for seconds or minutes, in the depth of the ear

B. Presence of a trigger area in the posterior wall of the auditory canal

C. Not attributed to another disorder

A trial of the anticonvulsant drug carbamazepine is common for patients diagnosed with GN. For patients who do not tolerate or respond to carbamazepine, alternative drugs include oxcarbazepine, gabapentin, phenytoin, lamotrigine, and baclofen. In addition, tricyclics (e.g., amitriptyline) and pregabalin are useful in other types of neuropathic pain.

In 1995, the Food and Drug Administration (FDA) approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.

In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck (Zostavax) against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence shows that it reduces the incidence of postherpetic neuralgia. The CDC recommends use of this vaccine in all persons over 60 years old.

As diagnostic criteria have been indecisive and its pathophysiology remains unclear, no permanent cure is available. Antiepileptic medications (membrane-stabilizing drugs) such as pregabalin, gabapentin, topiramate, and lamotrigine improve symptoms, but there is no effective permanent or long-term treatment for SUNCT.

However, a few short-term treatments are available and can relieve and possibly prevent some symptoms of attacks.

Lamotrigine exhibits some long-term prevention and reduction in many patients; however, titration of dose is difficult due to adverse skin reactions.

Topiramate also has preventive effects but it is accompanied by a high risk of severe side-effects for patients with a history of kidney stones, glaucoma, depression, or low body weight.

Intravenous lidocaine can abolish symptoms during its administration, or reduce frequency and duration of attacks. However, administration of intravenous lidocaine requires careful monitoring of ECG and blood pressure.

Methylprednisolone therapy shows some promise in short-term prevention of attacks, even though its mechanism of action is yet to be discovered.

The calcium channel blocker verapamil is reported to be useful in alleviating symptoms (lower frequency and duration of attacks), even though some patients experience worsened symptoms.

Various medications that are often used in other headache syndromes such as nonsteroidal anti-inflammatory drugs, acetaminophen, tricyclic antidepressants, calcium channel antagonists do not relieve the symptoms of SUNCT.

There have been attempts to alter oxygen supply during attacks to alleviate the symptoms since some of the headaches are caused by decreased oxygen supply; however, elevated blood oxygen level did not affect the symptoms.

Researchers now focus on the administration of various combination of medications and therapies to treat symptoms of SUNCT.

Hemicrania continua generally responds only to indomethacin 25–300 mg daily, which must be continued long term. Unfortunately, gastrointestinal side effects are a common problem with indomethacin, which may require additional acid-suppression therapy to control.

In patients who are unable to tolerate indomethacin, the use of celecoxib 400–800 mg per day (Celebrex) and rofecoxib 50 mg per day (Vioxx - no longer available) have both been shown to be effective and are likely to be associated with fewer GI side effects. There have also been reports of two patients who were successfully managed with topiramate 100–200 mg per day (Topamax) although side effects with this treatment can also prove problematic.

Greater Occipital Nerve [GON] block comprising 40 mg Depomedrone and 10mls of 1% Lignocaine injected into the affected nerve is effective, up to a period of approximately three months. Changing the 'cocktail' to include [for example] 10mls of .5% Marcaine and changing to 2% Lignocaine, whilst in theory should increase the longevity, renders the injection completely ineffective. See 4.2 Posology and method of administration [flocculation]

Occipital nerve stimulation may be highly effective when other treatments fail to relieve the intractable pain.

SUNCT must be properly distinguished from cluster headaches, since cluster headaches also occur several times per day with separate attacks, and share some common symptoms. However, cluster headaches usually last longer (up to three hours), occur less often (three to five attacks per day), and do not accompany cranial autonomic symptoms. IHS standard criteria for the diagnosis of SUNCT specifically includes pain in the trigeminal division of the face, especially in the orbital region, often with cranial autonomic symptoms which last for relatively short periods of time (from five seconds to several minutes) up to 100 times per day. SUNCT is a major subset of SUNA, which does not accompany cranial symptoms; complete separation between the two is inappropriate since SUNCT does not necessarily always accompany cranial autonomic signs. Exact statistical data is not available due to common mis-diagnosis, and setting up diagnostic criteria is important.

The International Headache Classification established by the International Headache Society criteria for diagnosing SUNCT for therapeutic purposes is:

Symptoms of SUNCT often lead to misdiagnosis as paroxysmal hemicrania, which is also categorized in the same group. Inefficiency of indomethacin usually indicates SUNCT over paroxysmal hemicrania.

Misdiagnosis and indecisive diagnosis in the past has made it difficult to obtain accurate statistics about SUNCT. Proper diagnosis will broaden data availability and facilitate discovery of new treatment options and useful statistics.

PNE can be caused by pregnancy, scarring due to surgery, accidents and surgical mishaps. Anatomic abnormalities can result in PNE due to the pudendal nerve being fused to different parts of the anatomy, or trapped between the sacrotuberous and sacrospinalis ligaments. Heavy and prolonged bicycling, especially if an inappropriately shaped or incorrectly positioned bicycle seat is used, may eventually thicken the sacrotuberous and/or sacrospinous ligaments and trap the nerve between them, resulting in PNE.

Various diagnostic systems have been described. Some consider the Research Diagnostic Criteria method the gold standard. Abbreviated to "RDC/TMD", this was first introduced in 1992 by Dworkin and LeResche in an attempt to classify temporomandibular disorders by etiology and apply universal standards for research into TMD. This method involves 2 diagnostic axes, namely axis I, the physical diagnosis, and axis II, the psychologic diagnosis. Axis I contains 3 different groups which can occur in combinations of 2 or all 3 groups, (see table).

McNeill 1997 described TMD diagnostic criteria as follows:

- Pain in muscles of mastication, the TMJ, or the periauricular area (around the ear), which is usually made worse by manipulation or function.

- Asymmetric mandibular movement with or without clicking.

- Limitation of mandibular movements.

- Pain present for a minimum of 3 months.

The International Headache Society's diagnostic criteria for "headache or facial pain attributed to temporomandibular joint disorder" is similar to the above:

- A. Recurrent pain in one or more regions of the head or face fulfilling criteria C and D

- B. X-ray, MRI or bone scintigraphy demonstrate TMJ disorder

- C. Evidence that pain can be attributed to the TMJ disorder, based on at least one of the following:

- pain is precipitated by jaw movements or chewing of hard or tough food

- reduced range of or irregular jaw opening

- noise from one or both TMJs during jaw movements

- tenderness of the joint capsule(s) of one or both TMJs

- D. Headache resolves within 3 months, and does not recur, after successful treatment of the TMJ disorder

Similar to a tinel sign digital palpitation of the ischial spine may produce pain. In contrast, patients may report temporary relief with a diagnostic pudendal nerve block (see Injections), typically infiltrated near the ischial spine.

Electromyography can be used to measure motor latency along the pudendal nerve. A greater than normal conduction delay can indicate entrapment of the nerve.

Imaging studies using MR neurography may be useful. In patients with unilateral pudendal entrapment in the Alcock's canal, it is typical to see asymmetric swelling and hyperintensity affecting the pudendal neurovascular bundle.

It has been suggested that the natural history of TMD is benign and self-limiting, with symptoms slowly improving and resolving over time. The prognosis is therefore good. However, the persistent pain symptoms, psychological discomfort, physical disability and functional limitations may detriment quality of life. It has been suggested that TMD does not cause permanent damage and does not progress to arthritis in later life, however degenerative disorders of the TMJ such as osteoarthritis are included within the spectrum of TMDs in some classifications.

The cause of hemicrania continua is unknown. There is no definitive diagnostic test for hemicrania continua. Diagnostic tests such as imaging studies may be ordered to rule out other causes for the headache. When the symptoms of hemicrania continua are present, it's considered "diagnostic" if they respond completely to indomethacin. The efficacy of indomethacin may not be long term for all patients, as can eventually become ineffective.

The factor that allows hemicrania continua and its exacerbations to be differentiated from migraine and cluster headache is that hemicrania continua is completely responsive to indomethacin. Triptans and other abortive medications do not affect hemicrania continua.

Trigeminal autonomic cephalgia (TAC) is the name for a type of primary headache that occurs with pain on one side of the head in the trigeminal nerve area and symptoms in autonomic systems on the same side, such as eye watering and redness or drooping eyelids. TACs include

- Cluster headache

- Paroxysmal hemicrania (chronic or episodic)

- Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)

- Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)

- Long-lasting autonomic symptoms with hemicrania (LASH)

TACs can be differentiated by the length and frequency of recurrence of the headaches.

Treatment for TACs varies depending on the exact type, but can include medication such as Indomethacin (in the case of chronic paroxysmal hemicrania) or acute and prophylactic therapy (in the case of cluster headache).

To relieve pain, some doctors suggest pressing the tongue against the roof of the mouth to warm the area, tilting the head back for 20 seconds, or drinking something warmer than whatever caused the headache. Some people report relief from breathing in through the mouth and out through the nose, thus passing warm air through the nasal passages.

Anesthesia dolorosa or anaesthesia dolorosa or deafferentation pain is pain felt in an area (usually of the face) which is completely numb to touch. The pain is described as constant, burning, aching or severe. It can be a side effect of surgery involving any part of the trigeminal system, and occurs after 1–4% of peripheral surgery for trigeminal neuralgia. No effective medical therapy has yet been found. Several surgical techniques have been tried, with modest or mixed results. The value of surgical interventions is difficult to assess because published studies involve small numbers of mixed patient types and little long term follow-up.

- Gasserian ganglion stimulation is stimulation of the gasserian ganglion with electric pulses from a small generator implanted beneath the skin. There are mixed reports, including some reports of marked, some of moderate and some of no improvement. Further studies of more patients with longer follow-up are required to determine the efficacy of this treatment.

- Deep brain stimulation was found in one review to produce good results in forty-five percent of 106 cases. Though relief may not be permanent, several years of relief may be achieved with this technique.

- Mesencephalotomy is the damaging of the junction of the trigeminal tract and the periaqueductal gray in the brain, and has produced pain relief in a group of patients with cancer pain; but when applied to six anesthesia dolorosa patients, no pain relief was achieved, and the unpleasant sensation was in fact increased.

- Dorsal root entry zone lesioning, damaging the point where sensory nerve fibers meet spinal cord fibers, produced favorable results in some patients and poor results in others, with incidence of ataxia at 40%. Patient numbers were small, follow-up was short and existing evidence does not indicate long term efficacy.

- One surgeon treated thirty-five patients using trigeminal nucleotomy, damaging the nucleus caudalis, and reported 66% "abolition of allodynia and a marked reduction in or (less frequently) complete abolition of deep background pain."