Idiopathic orofacial pain

Summary

Idiopathic orofacial pain is a group of painful disorders affecting the facial region and/or oral cavity with unclear etiology. This group includes burning mouth syndrome, persistent idiopathic dentoalveolar pain, persistent idiopathic facial pain, and constant unilateral facial pain with additional attacks. These are acquired diseases of adulthood, most commonly affecting postmenopausal women. The etiology of these disorders is not entirely understood, but likely involves changes at both the peripheral and central levels of the somatosensory system, including small fiber neuropathy, subclinical peripheral neuropathy, alterations in brainstem functions, and changes in central inhibitory pain modulation. Although some patients mistakenly consider dental treatment as the triggering situation, a causal relationship with invasive procedures in the oral cavity has not been unequivocally proven. Diagnosis is based on evaluating the clinical characteristics of the pain and excluding secondary causes. Treatment strategies include acute topical application of certain medications or long-term off-label treatment (antidepressants, antiseizure medications). The effectiveness of pharmacological treatment may be limited, often due to side effects. Expert agreement is that early diagnosis and pharmacological therapy are positive prognostic factors, while repeated invasive procedures worsen the prognosis. Comorbid depressive and anxiety symptoms affect roughly one-third to one-half of patients. Psychosocial stress can exacerbate the disease course. Spontaneous improvement occurs in only a minority of patients (at most one-third), usually after two to seven years of disease duration. Providing sufficient information about the diagnosis and reassuring the patient about the neurobiological nature of the disease remains crucial. Supportive psychotherapeutic treatment is also recommended.

Keywords:

trigeminal neuralgia – facial pain – burning mouth syndrome – dentoalveolar pain

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Burning mouth syndrome

Persistent idiopathic dentoalveolar pain

Persistent idiopathic facial pain

Persistent unilateral facial pain with associated attacks

Introduction

Idiopathic orofacial pain

The idiopathic orofacial pain group is characterized by intraoral or facial pain of unknown etiology. It consists of four basic units: burning mouth syndrome (BMS), persistent idiopathic dentoalveolar pain (PIDAP), persistent idiopathic facial pain (PIFP), constant unilateral facial pain with additional attacks (CUFPA) (Tab. 1). For the first three entities, three subtypes are distinguished (no somatosensory changes, with somatosensory changes, and a probable diagnosis of BMS, PIDAP, or PIFP). There are not yet sufficient data to make a similar distinction for CUFPA [1].

 

Clinical picture

Epidemiological and demographic characteristics, risk factors and common comorbidities are similar for the whole group and are therefore summarised together in Table 2. Diagnosis is based only on the following clinical criteria:

anatomical localisation in the intraoral and/or facial region; not explained by a lesion of a peripheral nerve (trigeminal nerve and its branches, other cranial or cervical nerve);

the subjective characteristic of pain is not neuralgic, whiplash-like; it cannot be provoked by non-painful stimuli (touch, sniffing, chewing, etc.), the quality of pain is inconsistent (some patients may find it difficult to describe or use more complex analogies), the intensity of pain is highly variable and may fluctuate;

the temporal course of pain is persistent (continuous presence or daily episodes lasting > 2 h/day over an arbitrarily defined period of time > 3 months); it lacks the character of short paroxysms of intense pain with an abrupt beginning and end;

other local or systemic causes are excluded (diagnosis per exclusionem); diagnosis requires a multidisciplinary approach [1].

 

Pathophysiology

Idiopathic orofacial pain is characterized by dysfunction of the somatosensory system leading to pain in the craniofacial region, and this pain cannot be declared as nociceptive (no clear evidence of actual or threatened tissue damage causing activation of peripheral nociceptors) or neuropathic (no evidence of disease or lesion of the somatosensory system causing pain) [1]. Therefore, a nociplastic type of pain is considered in the pathophysiology (Table 4), but in which the absence of evidence of damage to peripheral tissues or the somatosensory system does not exclude a possible nociceptive or neuropathic component. The very existence and conditions for the use of the term nociplastic pain are not accepted entirely without reservation [2-4]. On the contrary, the phenotypic diversity of idiopathic orofacial pain (focal or regional involvement, burning or dull character of pain, possible presence of somatosensory abnormalities, etc.) has led some authors to emphasize the different mechanisms that may be involved in the generation and maintenance of nociplastic pain. Published hypotheses for the origin of idiopathic orofacial pain include focal small fiber neuropathy (demonstrated by a reduction in the density of intraepidermal small nerve fibers from tongue biopsy [5,6]), up-regulation of the capsaicin receptor TRPV1 and purinergic receptor P2X3 in tongue biopsy (expression of both receptors is modulated by estrogens) [6-8], and chorda tympani hypofunction [9] with reduced basal salivary secretion and different salivary composition, all in patients with BMS [10,11]. The hypothetical possibility of microtraumatization (e.g., anesthetic injection into peripheral tissues or intraneural injection, endodontic treatment) has been considered in patients with PIDAP [12]. Subclinical peripheral neuropathy has been described in patients with PIFP (e.g., entrapment in the foramen rotundum or foramen ovale) [13]. In addition to peripheral mechanisms, the role of central pain processing (particularly the influence of the dopaminergic system) has been emphasized, but may apply to different degrees in different diagnoses. For example, it has been proposed to divide diagnoses into subgroups with predominantly peripheral and predominantly central BMS or PIDAP (according to the outcome of a therapeutic test, whereby pain temporarily subsides in some patients during local anaesthesia) [14,15]. Alterations of subcortical and cortical structures involved in pain processing have been demonstrated as secondary correlates of chronic pain in patients with BMS and PIFP, as detected by advanced neuroimaging methods (e.g., functional MRI [fMR], MR volumetry, PET) [16-19]. In summary, therefore, the following are essential for understanding the pathophysiology of idiopathic orofacial pain:

1)
Nociplastic pain is caused by a change in the nociceptive process, even without clear evidence of actual or threatened tissue damage causing activation of peripheral nociceptors (nociceptive pain) or evidence of disease or lesion of the somatosensory system causing pain (neuropathic pain). However, a possible nociceptive and/or neuropathic component is permissible [1,3].

2)
Despite the unclear aetiology, idiopathic orofacial pain preserves the principle of the convergence of peripheral nociceptive stimuli at the level of the trigeminocervical complex (nucleus caudalis nerves trigemini and posterior horns of spinal segments C2 and C3) and thalamus, the process of central sensitization and impaired central modulation (descending inhibition and endogenous facilitation) of pain. Brainstem structures, the limbic system and some cortical areas (anterior cingulum, insula, ventromedial and dorsolateral frontal cortex) are involved in cognitive processing and affective regulation of pain, and their activation is associated with psycho-behavioural consequences of pain (anxiety, depression, hypervigilance, etc.) [1,20].

 

Burning mouth syndrome (BMS)

Formerly used names: stomatodynia/glossodynia, burning mouth syndrome, primary burning mouth syndrome

Burning mouth syndrome is defined by a burning pain felt on the surface of the intact oral mucosa (daily for at least two hours over a period of at least three months) [1]. The most common location is the tip of the tongue (dorsum or margin of its anterior two-thirds); other distributions (hard palate, lips, gums, pharynx) are not very common (Figure 1). The lesion is usually symmetrical but may be unilateral and/or multilocular. The character of the pain is usually described as burning or stinging. Pain intensity is variable (mild to high), may fluctuate, and some patients complain of an increase in intensity associated with stress [21,22]. The clinical division of BMS into type 1 (asymptomatic on awakening, increasing in intensity during the day, evening peak), type 2 (continuous symptoms sometimes interfering with sleep) and type 3 (intermittent symptoms present only some days) has been abandoned [23]. Up to two-thirds of patients with BMS have taste changes (dysgeusia), with a metallic aftertaste being the most frequently mentioned symptom, and a dry mouth sensation (xerostomia) is common [22]. It is necessary to exclude common secondary causes of glossodynia and stomatodynia (exposure to angiotensin converting enzyme inhibitors, B12, folate and zinc deficiency). Pharmacological treatment of BMS consists of topical or systemic administration of drugs whose efficacy is not directly comparable (also the level of evidence of effects varies between studies). Topical application of clonazepam 0.5-3.0 mg/day (drops or tablets dissolved in the mouth, held in saliva and spat out after three minutes) is considered the first choice treatment. The effect is relatively rapid, lasts 4-5 h (administration in three divided doses is therefore possible) and leads to a reduction in pain intensity of 1.5 points on a 10-point scale in three-quarters of patients [24]. Topical application of a gel containing a local anaesthetic (lidocaine) is not commonly used, nor is capsaicin (due to adverse gastrointestinal effects). Rather, neutral, physically acting gels such as artificial saliva or tasteless lozenges may be recommended. Systemic treatment includes clonazepam (0.5-2.0 mg/day; however, there is a risk of developing dependence with long-term use), amitriptyline (12.5-25 mg/day; due to the anticholinergic effect, possible worsening of dry mouth), fluoxetine (20-40 mg/day), pregabalin (75-150 mg/day) or gabapentin (minimum 300 mg/day). Combination treatment with one of the systemically administered drugs and topical clonazepam as needed may also be advantageous. Treatment with alpha-lipoic acid (600-800 mg/day for one or two months) is considered a likely effective and safe option [25,26].

 

Persistent idiopathic dentoalveolar pain (PIDAP)

Formerly used names: atypical odontalgia, primary persistent dentoalveolar pain disorder (PDAP), phantom tooth pain

Persistent idiopathic dentoalveolar pain is characterised by persistent pain in the dentoalveolar region (present daily for more than two hours over a period of more than three months). The typical phenotype is a dull, pressing pain felt deep within the tooth or jaw [1]. Less reliable characteristics of PIDAP include unilateral and monolateral occurrence of pain, with a predominance in the maxillary and posterior regions rather than the mandibular and anterior regions (Figure 2). The first molar region is most commonly affected and most patients underwent their endodontic treatment. The temporal course of pain is variable (up to 80% of patients have a pain-free morning period, possible increase in pain intensity with stress or changes in atmospheric pressure), but it is not characterized by acute paroxysms and remissions [27-29]. A frequently used drug is amitriptyline 12.5-50 mg in an evening dose (four-month treatment resulted in at least 30% reduction in pain intensity in 66% of patients) [30]. Gabapentin (900-3,600 mg/day), pregabalin (150-600 mg/day) and duloxetine (20-40 mg/day) have been tested in small, heterogeneous cohorts of patients with orofacial pain (including PIDAP) [31]. Topical application of lidocaine may be beneficial for a proportion of patients with PIDAP, resulting in a mean reduction in pain intensity of 60% [32]. Topical lidocaine injection is not used in PIDAP due to the short therapeutic window (120 min) and rebound phenomenon in one third of patients [33]. Topical injection of botulinum toxin A (10-30 units) into 3-12 intraoral sites (interdental papillae, vestibular and fixed gingiva) appears to be more promising, resulting in at least 50% reduction in pain intensity with repeated treatments (every 12 weeks) [34].

 

Persistent idiopathic facial pain (PIFP)

Formerly used name: atypical facial pain

Persistent idiopathic facial pain is characterised by persistent facial pain (present daily for more than two hours over a period of more than three months). The pain is ill-defined, poorly localized, and does not fundamentally follow the anatomical distribution of the peripheral nerve (Figure 3). However, the area of the infraorbital nerve, which is the most common site of nociception even in trigeminal neuralgia, is almost never spared. Up to one-third of patients experience extension across the midline of the face, and pain may extend intraorally. The character of the pain is dull and unpleasant, felt vaguely deep in the tissues rather than superficially. Pain intensity is inter -⁠ and intra-individually variable. Similar to PIDAP, patients may report minor trauma or surgery as the triggering cause, although clinical and imaging findings are normal [1,35,36]. Amitriptyline (25-100 mg/day), venlafaxine (75-150 mg/day), fluoxetine (10-20 mg/day), and topiramate (25-100 mg/day) are recommended in the treatment of PIFP [37].

 

Constant unilateral facial pain with associated attacks (CUFPA)

Permanent unilateral facial pain with associated attacks is characterized by constant and strictly unilateral facial pain of low to moderate intensity, which is accompanied by distinct attacks of moderate to high intensity pain in the same localization and lasting 10-30 min. In contrast to PIFP, the patient clearly distinguishes between persistent (basal) pain and associated attacks (exacerbations). Basal pain is non-remitting but may fluctuate in intensity. The exacerbations of associated attacks occur spontaneously, are not neuralgic in nature, last 10-30 min, usually no more than 6 times a day. In the only described cohort of patients with CUFPA, six women aged 41-67 years were involved [38]. Indomethacin is not effective for basal pain or associated attacks; treatment with metamizol, ibuprofen, carbamazepine (400 mg/day) and pregabalin (150 mg/day) has been partially effective in some patients. In two patients, none of the empirically tested drugs (including opioids, antidepressants, anti-seizure medication and corticosteroids) provided relief [38].

 

General principles of diagnosis and treatment

Terminology

Orofacial pain as a symptom must be fundamentally distinguished from the diagnosis. For example, the overall prevalence of the symptom of burning pain in the oral cavity (regardless of the aetiology) is an order of magnitude higher (1-4%) than the prevalence of BMS (0.1%) [21,39]. To express the symptom, it is necessary to resort to older, more general terms (prosopalgia, stomatodynia, glossodynia, odontalgia). The correct nomenclature of the diagnoses is codified by the International Classification of Orofacial Pain (it also has a Czech translation) [1,40]. Obsolete names are given for each diagnosis only for completeness. The previously used nosological terms "atypical facial pain" or "atypical odontalgia" are not appropriate because they refer to an entity historically considered "typical" (trigeminal neuralgia).

 

Differential diagnosis

The first-line contact is usually a dentist, and a consultation at a specialised pain management centre occurs after several months or years of pain [38]. The diagnosis of orofacial pain requires a multidisciplinary approach and the use of paraclinical methods (Table 3, Table 4). The exclusion of local intraoral pathology is the task of the dentist -⁠ in terms of the number of possible clinical entities causing intraoral pain, this is the broadest differential diagnostic area. In addition to the pathology of teeth and related structures (periodontium, alveolar process, gingiva), attention should be paid to possible local lesions of the oral mucosa (caused by trauma, infection, autoimmune or other systemic diseases, hypersensitivity or allergic reaction) [1]. Myofascial orofacial pain is provoked by palpation of the masticatory muscles or by maximal opening of the mouth. Moreover, temporomandibular joint pain is accompanied by its dysfunction (limitation of movement, acoustic phenomena). Orofacial pain with symptoms resembling primary headaches is rare and has a clear seizure course with characteristic accompanying symptoms. Trigeminal neuralgia has a completely different clinical picture with brief attacks of high intensity shooting pain that can be provoked by normally innocuous stimuli. Post-traumatic trigeminal neuropathic pain most often arises iatrogenically (e.g. lesions of the nervus alveolaris inferior after extraction of the third mandibular molar, lesions of the nervus mentalis after application of a root filling to the mandibular canine) [1]. Pain and painless symptoms in the orofacial region (xerostomia, tactile hypesthesia, etc.) are part of a broader differential diagnosis (e.g., Sjögren's syndrome, numb chin syndrome, neuralgia in the ear region) [41,42].

 

Psychological aspects

In patients with idiopathic orofacial pain, we encounter general neuropsychological consequences of chronic pain that significantly affect the emotional experience of pain. Although they are not the cause of the disease, they may dominate the overall clinical impression in some patients . Negative affectivity is a stable tendency to experience a wide range of unpleasant and unproductive feelings for the patient (e.g., worry, anxiety, negative self-view). Anxiety is more closely related to hypervigilance: it refers in particular to the new experience of pain, where it becomes threatening to the patient and leads to the catastrophising of pain. Catastrophising is a specific phenomenon that includes rumination (negative ruminations), exaggeration (exaggerated ideas about possible developments, including carcerophobia) and helplessness (loss of control over the situation) [43]. Psychological distress and catastrophizing are compounded by the so-called perceived injustice, which subjectively accentuates the magnitude and irreversibility of the health loss and carries with it accusations (e.g. of misunderstanding and indifference by the environment). These and related phenomena on the part of the patient may lead to the indication of unhelpful and repeated examinations or erroneous reasoning about the non-organic origin of the pain or, on the contrary, to the attempt to find a radical solution (e.g. endodontic and reendodontic treatment, root tip amputation, tooth extraction, dental implants). Last but not least, they can cause feelings of frustration in the treating physicians and otherwise disrupt the patient-therapist relationship [43,44].

 

Patient education and prevention of further damage

When communicating with the patient, it is advisable to spend sufficient time describing the symptoms in detail, which will facilitate subsequent cooperation, may increase tolerance and a sense of control of the symptoms and induce the patient to take the initiative. On the other hand, many patients are burdened, to varying degrees, with elements of cognitive bias (misconceptions about the cause, misconceptions about the disease, irrational beliefs about symptoms, carcerophobia, etc.). Basic education should include information about the diagnosis, the real and authentic experience of pain despite the absence of tissue damage, and especially information about the complex, neurobiological nature of the disease. The patient can monitor and possibly influence exposure to mucosal irritants (spicy foods, hot foods, carbonated beverages, chewing gum, mentholated dragees, toothpaste, cosmetics, smoking and vaping). Awareness of parafunctional oral activities (e.g., touching the tip of the tongue to the teeth, avoiding tongue protrusion or abrasion, clenching of the masticatory muscles, lip clenching) is also appropriate [45]. Unwarranted invasive dental procedures or interference with tissue integrity by the patient themselves are completely undesirable.

 

Pharmacological and non-pharmacological treatment

In general, the treatment strategy for idiopathic orofacial pain is symptomatic only, with the predominant indication of adjuvant analgesics (antidepressants, anti-seizure medication, etc.). The efficacy of pharmacological treatment is limited and sometimes limited by adverse effects. Nevertheless, experts agree that early diagnosis and initiation of pharmacological therapy are positive prognostic factors for the future course of the disease. While the indication of opioids is not recommended, cannabis has an interesting perspective for medical use [46]. If the patient is interested, simple supportive techniques can be tried -⁠ lubrication of the oral cavity with an indifferent solution (the patient holds it in the mouth for a few minutes 3-4 times a day) or relaxation exercises targeting the masticatory and mimic muscles. Cognitive behavioral therapy should accompany pharmacotherapy for chronic pain when possible [37]. The following interventional and neurostimulation interventions have not been shown to have a positive effect in PIFP (e.g. are not recommended): block of the nervus occipitalis major or ganglion stellatum, pulsed radiofrequency treatment of the sphenopalatine ganglion, microvascular decompression of the trigeminus, Leksell gamma knife treatment, conventional transcutaneous stimulation, repetitive transcranial magnetic stimulation of the secondary somatosensory cortex, spinal cord stimulation in the upper thoracic region [37,47].

 

Conclusion

Idiopathic orofacial pain is a set of clinical entities whose diagnosis and treatment pose a challenge to physicians of various specialties. This is due to the lack of a structural correlate to explain the patient's difficulties, as well as limited interdisciplinary collaboration. Thus, the correct diagnosis is commonly made after a time delay, often after undergoing unnecessarily invasive dental treatments. There is consensus that early and correct diagnosis and pharmacological therapy are positive prognostic factors in the management of these diseases. Conversely, repeated invasive procedures worsen the prognosis. Nevertheless, only about one third of patients achieve significant improvement. Thus, communication and provision of sufficient information to patients, as well as reassurance about the neurobiological nature of the disease, remains a crucial element. Supportive psychotherapy is desirable but generally underused in chronic pain.

 

Conflict of interest

The authors have no conflicts of interest related to the work.

 

Acknowledgements

The authors would like to thank Maxdorf -⁠ graphic studio for the pictures.

 

Table 1. Clinical criteria of idiopathic orofacial pain units according to ICOP [1].

Burning mouth syndrome (BMS)

A. oral pain meeting criteria B and C B. recurring daily for > 2 h for > 3 months C. pain has both of the following characteristics: 1. a burning quality 2. felt on the surface of the oral mucosa D. the oral mucosa has a normal appearance and local or systemic causes have been excluded E. not better classified under another ICOP or ICHD-3 diagnosis

Persistent idiopathic dentoalveolar pain (PIDAP)

A. intraoral dentoalveolar pain meeting criteria B and C B. recurring daily for > 2 h for > 3 months C. pain has both of the following characteristics: 1. localized in the dentoalveolar region (tooth or alveolar process) 2. deep, dull or pressure quality D. clinical and radiological findings are normal and local causes have been excluded E. not better classified under another ICOP or ICHD-3 diagnosis

Persistent idiopathic facial pain (PIFP)

A. facial pain meeting criteria B and C B. recurring daily for > 2 h for > 3 months C. pain has both of the following characteristics: 1. poorly localized and inconsistent with peripheral nerve distribution 2. a dull, burning or bothersome quality D. clinical and radiological findings are normal and local causes have been excluded E. not better classified under another ICOP or ICHD-3 diagnosis

Constant unilateral facial pain with associated attacks (CUFPA)

A. persistent, strictly unilateral facial pain meeting criterion B, with exacerbations meeting criterion C B. persistent pain has both of the following characteristics: 1. mild to moderate intensity 2. persistently present for > 3 months C. exacerbations occur up to six times a day as distinct attacks of pain that has all three of the following characteristics: 1. in the same localization as the persistent pain 2. moderate to high intensity 3. lasting 10-30 min D. clinical and radiological findings are normal and local causes have been excluded E. not better classified under another ICOP or ICHD-3 diagnosis

ICOP -⁠ International Classification of Orofacial Pain; ICHD-3 -⁠ International Classification of Headache Disorders

 

 

Table 2: Epidemiology and common clinical characteristics of idiopathic orofacial pain. 

Idiopathic orofacial pain is uncommon or rare. The prevalence of BMS is reported to be 0.1% of the general population [39]. The lifetime prevalence of PIFP is estimated to be 0.03% [48]. The prevalence of PIDAP in the general population is less than 0.1%, but 3-4% in patients who have undergone endodontic treatment [49].

 

The predominant affected population is female. The ratio of female to male involvement is reported to be 7-10 : 1 for BMS [50], 3-8 : 1 for PIDAP [51] and 3 : 1 for PIFP [36].

 

The development occurs most often in middle age and reaches its highest prevalence in old age. The development of BMS has been observed in adulthood, and its prevalence increases with age, reaching a maximum in the age group 60-80 years [21,39]. The highest prevalence of PIDAP is estimated between the fourth and sixth decades [51]. The age at development of PIFP ranged from 17-74 years with a mean age of 44 years [36].

 

Dental treatment was reported as the triggering cause by most patients. One-fifth of patients after endodontic treatment suffer from intense pain lasting more than one week (acute dental pain or periodontal pain) [1,31]. However, PIDAP occurs in only 3-6% of patients after previous endodontic treatment [52]. Yet, 57-83% with PIDAP retrospectively identify an invasive dental or ostomy procedure as the trigger [28,52]. Conversely, 30% of patients with PIFP underwent invasive dental treatment after the disease developed in an attempt to cure [36]. Patients with BMS may relate to disinfectant rinses during endodontic treatment or dental restorations [53]. 

Idiopathic orofacial pain may be multilocalized and have a progressive course. One third of patients with BMS and half of patients with PIDAP experience pain in more than one intraoral localization [21,28]. Bilateral localization of pain has been observed in 39% of patients with PIDAP and 13% of patients with PIFP [28,36]. In 17% of PIFP patients, there is a progressive spread to the wider craniocervical region beyond the trigeminal distribution [36].

Psychiatric comorbidities are relatively common; exacerbation of pain by psychological distress is possible.  Anxiety symptoms and depression have been diagnosed in 48% and 35% of patients with BMS [54], 10% and 15% of patients with PIDAP [28], and 13% and 30% of patients with PIFP [36], respectively. Aggravation of pain by psychological distress was reported in 17% of PIFP patients [36].

The prognosis of the disease is rather less favorable. Of 53 patients with BMS (mean duration of complaints 5.5 years, minimum follow-up 18 months), 50% observed no change in symptoms, 20% reported worsening, and 30% experienced symptom relief (spontaneous remission in only 3% of patients) [55]. A negative prognostic factor for treatment response in BMS is xerostomia at the start of follow-up and persistent dysgeusia [56]. During a follow-up period of seven years, 35% of patients with PIDAP improved significantly (only 14% were completely pain-free), and low pain intensity at the beginning of follow-up was a predictor of improvement [57]. Periods of remission longer than one month occur in approximately 20% of patients with PIDAP [36].

BMS, burning mouth syndrome; PIDAP, persistent idiopathic dentoalveolar pain; PIFP, persistent idiopathic facial pain

 

 

Table 3. Diagnostic procedure and paraclinical examinations in idiopathic orofacial pain.

History: dental anomalies, dental fillings (galvanism, contact allergies), fixed orthodontic/prosthetic appliances, mechanical/thermal/chemical/advisory damage, use of angiotensin converting enzyme inhibitors, oral antidiabetic drugs, chemotherapeutic drugs (side effects), long-term application of topical antiseptics, long-term antibiotic treatment, food preservatives (e.g. Sorbic acid, benzoic acid), cosmetic ingredients and toothpaste (e.g. sodium lauryl sulfate) [23,53].

Dental examination including orthopantomography ev. CT with cone beam CT: Disease of the tooth, periodontium, gingiva, oral mucosa, jaw, salivary glands [1], in 90% of PIDAP patients the area of mechanical allodynia of the gingival sulcus can be examined -⁠ usually extending to the adjacent tooth in the same quadrant, affecting two quadrants (30%), three quadrants (15%), four quadrants (8%) [27].

ENT examination incl. X-ray of paranasal sinuses, ev. CT of the facial skeleton: local pathological process (local metastasis, perineural metastatic spread, etc.) [41,58].

Neurological examination: orientation examination of facial sensitivity by qualitative methods (tactile and thermal sensitivity), in case of abnormality in peripheral nerve distribution, exclusion of peripheral neuropathy in malignancy [41]; in idiopathic orofacial pain, a definite pathognomonic profile cannot be established even with quantitative sensitivity testing [59]

MRI of the brain: to exclude lesions in the skull base, leptomeningeal infiltration, neurovascular conflict (dislocation and/or atrophy) with the ipsilateral trigeminal nerve [36,41]

Laboratory screening: Within the range usual in polyneuropathies (blood count, erythrocyte sedimentation rate, sodium, potassium, chloride, zinc, glucose, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, C-reactive protein, total serum proteins, serum protein electrophoresis, cryoglobulins, lipids, thyrotropin, free thyroxine, serum vitamin B12 and folic acid levels, serological testing for antiborrelial antibodies) [23,53].

Other optional investigations: dermatology, mucosal biopsy, microbiological examination including cultures (bacteria, yeast), sialometry (Škach test), Schirmer test, endoscopic examination of the oesophagus, scintigraphy or salivary gland biopsy [23,53]

 

 

Table 4. Pain is an unpleasant sensory experience associated with, or similar to, actual or potential tissue damage. From a pathophysiological point of view, it is divided into three basic types, examples of which are given in the orofacial region [1,60].

Pain type	General definition	Examples
nociceptive pain	Pain arises as a consequence of actual or threatened damage to peripheral tissue that causes activation of nociceptors. It is an expression of the normal function of the somatosensory nervous system.	pain in the dental pulp in connection with exposed dentin   dental pulp pain associated with irreversible pulpitis caused by caries affecting the pulp cavity   periodontal pain in connection with chronic periodontitis   gingival pain related to gingivitis   oral mucosal pain related to radiation or chemotherapy   jaw pain related to a local malignant lesion   myofascial orofacial pain related to muscle spasm   temporomandibular joint pain related to degenerative joint disease
neuropathic pain	Pain arising as a consequence of a lesion or disease affecting the somatosensory system.	Classical trigeminal neuralgia   secondary trigeminal neuralgia related to multiple sclerosis   secondary trigeminal neuralgia in association with a structural lesion   idiopathic trigeminal neuralgia   trigeminal neuropathic pain in association with acute herpes zoster infection   postherpetic trigeminal neuralgia   post-traumatic trigeminal neuropathic pain
nociplastic pain	Pain is caused by a change in nociception, even without clear evidence of actual or threatened tissue damage causing activation of peripheral nociceptors or even without evidence of disease or lesion of the somatosensory nervous system causing pain.	Burning mouth syndrome (BMS) Persistent idiopathic dentoalveolar pain (PIDAP) Persistent idiopathic facial pain (PIFP) persistent unilateral facial pain with associated attacks (CUFPA)