Neuropathic orofacial pain: a narrative review of mechanisms, differential diagnosis, and management

Introduction

Background

JK | Revised text

Neuropathic pain (NP) is a pain syndrome defined by the International Association for the Study of Pain (IASP) as "pain caused by a lesion or disease of the somatosensory system" (1). It is characterized by unpleasant symptoms, including shooting, electric-like, or burning sensations, numbness, altered sensations, and sensations that are difficult to describe (2). The lesion or disease resulting in an abnormal and dysfunctional somatosensory nervous system is the primary cause of NP. In contrast, nociceptive pain involves peripheral sources of noxious stimuli that are processed by an otherwise normally functioning somatosensory nervous system (3). Standard analgesics are relatively ineffective in treating NP. Evidence-based treatment guidelines recommend treatment with antiepileptics, antidepressants, and/or topical medications, and nonpharmacological approaches (4-6). Patients with NP often receive inadequate treatment despite the existence of established guidelines and medications (7). Enhancing awareness among healthcare providers and patients is essential for achieving better outcomes in managing chronic NP.

Rationale and knowledge gaps

Neuropathic orofacial pain (NOP) is a distinct category of disorders affecting the orofacial region, requiring specialized attention and treatment. The trigeminal nerve plays an indispensable role in the orofacial region, transmitting pain signals from peripheral nociceptors to the thalamus and cerebral cortex. Modulating systems and individual factors, such as cognition, behavior, emotions, and motivation, influence the final perception of pain (8). Assessing patients with chronic orofacial pain can be complex. Notably, NOP poses a significant challenge for clinicians, as its symptoms can mimic those of odontogenic pain. The first comprehensive classification of orofacial pain, the International Classification of Orofacial Pain (ICOP), was published in 2020 (9).

Neuropathic orofacial pain is defined by a lesion or disease of the somatosensory system, rather than by pain quality alone (1). For dentists, the clinical challenge is to recognize neuropathic presentations, distinguish them from odontogenic disease, and choose appropriate management. Previous reviews have considered neurophysiological assessment of chronic neuropathic orofacial pain (10) and the broader spectrum of orofacial pain disorders (11). This narrative review connects mechanistic evidence with clinical assessment and treatment, focusing on trigeminal neuralgia (TN) and on the proposed neuropathic mechanisms and overlapping presentations of burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), and persistent idiopathic dentoalveolar pain (PIDP). These idiopathic conditions are discussed because of their relevance to differential diagnosis and the mechanistic literature; their inclusion does not imply a confirmed neuropathic cause in every patient. ICOP and the International Classification of Headache Disorders, 3rd edition (ICHD-3), provide the classification framework (9,12).

Objective

This narrative review examines the mechanisms, differential diagnosis, and management of neuropathic orofacial pain for dentists and other healthcare professionals. The clinical discussion centers on TN and the neuropathic mechanisms proposed in BMS, PIFP, and PIDP, while distinguishing these idiopathic diagnoses from pain attributable to an established somatosensory lesion or disease. Assessment, treatment, and referral are considered within ICOP and ICHD-3 frameworks. A brief overview of pediatric pain assessment provides supplementary clinical context. We present this article in accordance with the Narrative Review reporting checklist (available at https://fomm.amegroups.com/article/view/10.21037/fomm-2025-1-50/rc).

Methods

A literature search was performed using PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science, from database inception through March 2025 (Table 1). Only English-language publications were included, with no restrictions on study design. Search terms included neuropathic pain, facial nerve, trigeminal neuralgia, neuralgia, therapy, and etiology, combined using the Boolean operators AND and OR. Two authors (S.A. and A.V.) independently screened titles and abstracts and identified and analyzed relevant studies. Disagreements were resolved through discussion and consultation with a third researcher (J.K.). Reference lists of relevant original research and review articles were also hand-searched to identify studies that might have been overlooked. Sixty manuscripts were included in the review.

Pediatric pain assessment: general considerations

Pain assessment should be adapted to the child's developmental stage, communication abilities, and clinical context. In preterm infants, neonates, and young children, observational tools used primarily for acute or procedural pain include the Premature Infant Pain Profile (PIPP), Douleur Aiguë du Nouveau-né (DAN), Neonatal Infant Pain Scale (NIPS), Neonatal Facial Coding System (NFCS), Évaluation Enfant Douleur (EVENDOL), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), and Face, Legs, Activity, Cry, Consolability (FLACC) scale. When developmentally appropriate, children can self-report pain using the Faces Pain Scale-Revised, visual analog scale, numerical rating scale, or verbal rating scale (13). These tools provide general pediatric assessment context; pain-intensity scores alone do not establish a diagnosis of TN, BMS, PIFP, or PIDP, which requires condition-specific clinical assessment.

NOP

According to the new classification, NOP is classified into two broad categories:

Orofacial pain attributed to a lesion or disease of the cranial nerve (16)

• Pain attributed to lesion or disease of the trigeminal nerve:
  • TN:
    • Classic TN;
    • Secondary TN.
  • TN and other trigeminal NP:
    • Trigeminal NP attributed to herpes zoster;
    • Trigeminal post-herpetic neuralgia;
    • Post-traumatic trigeminal pain.
• Pain attributed to lesion or disease of the glossopharyngeal nerve. ICHD-3(H/a classification cephalgia) includes other, less common entities.

Idiopathic orofacial pain (16)

• BMS;
• Persistent idiopathic facial pain (PIFP);
• Persistent idiopathic dentoalveolar pain (PIDP).

This manuscript will discuss the most common clinical presentation of NOP, a topic relevant to dentists.

• TN;
• BMS;
• PIFP/PIDP.

TN

TN is described as a paroxysmal NP condition marked by short-lasting, electric shock-like pain, typically triggered by non-painful stimuli. The location of pain corresponds to the course of the trigeminal nerve divisions (17,18). About half of TN patients experience concomitant continuous pain, characterized by dull, aching, or burning pain of reduced intensity superimposed on the areas of paroxysmal pain (19). It is estimated that in approximately 97% of TN patients, paroxysms were linked to triggers (20-22). Historically, at the end of the first century, Aretaeus of Cappadocia (23) described a condition (heterocrania) where ‘‘spasm and distortion of the countenance take place”. It wasn’t until 1677 that John Locke correctly identified that facial pain was caused by the trigeminal nerve and not of odontogenic origin (24).

TN is a relatively uncommon condition, and as a result, epidemiological studies on the topic are scarce in existing literature. The prevalence of TN is approximately 200.2 per million women and 107.5 per million men. And the overall prevalence in the general population is about 0.015% (25). TN predominantly affects adults aged 60 years and older, with a higher incidence in women. This condition most commonly affects the right side and the mandibular branch of the trigeminal nerve. An epidemiological study revealed depression, heightened anxiety, and disturbed sleep in patients with TN, emphasizing the condition’s impact on mental health (26,27). Recent advances in understanding the pathophysiology, etiology, symptomatology, and imaging of TN have resulted in a revised classification system. This new system, endorsed by the IASP and others, is outlined in the ICOP classification (Table 2). The revised classification system renames “classical TN” as either “classic” or “idiopathic TN”, based on the presence of neurovascular contact (16). Additionally, TN caused by other underlying conditions, such as tumors or multiple sclerosis, is now referred to as “secondary TN”. According to the International Classification of Headache Disorders (ICHD-3), TN is defined as recurrent, severe, paroxysmal pain limited to the trigeminal territory, lasting from a fraction of a second to 2 minutes, with pain described as electric-shock-like, stabbing, or sharp, and triggered by innocuous stimuli (28). The long-held theory that neurovascular compression, typically caused by the superior cerebellar artery, leads to TN through demyelination and abnormal firing has faced challenges. While compression is often observed, many TN patients lack evidence of it, and it is also commonly seen in individuals without symptoms. This has prompted researchers to explore alternative explanations for TN's pathophysiology. One such model, the “ignition hypothesis”, proposes that partly damaged trigeminal root neurons become hyperexcitable, characterized by spontaneous bursts and increased sensitivity (29). Carbamazepine, a first-line medication for TN, has made voltage-gated sodium channels an appealing target for investigating the origin of ectopic nerve activity (30). Various ion channels, including calcium, potassium, and chloride channels, are also being investigated. A review of the current literature reveals an exploration of multiple potential pathophysiological mechanisms, with no definitive frontrunner, suggesting that TN may have various causes (31-33).

TN diagnosis relies on a comprehensive clinical evaluation, including a detailed medical history of pain episodes meeting established diagnostic criteria, physical examination findings, and results of cranial imaging studies. Because TN typically presents with acute bouts of severe pain in the lower face triggered by perioral stimuli, the condition is often misdiagnosed as dental issues or pathology (34). When examining a patient with suspected TN, it is crucial to begin with a comprehensive medical and dental history and a detailed account of the presenting symptoms. Any unusual neurological findings should be further investigated, as they may suggest secondary TN-related issues. However, sensory abnormalities, such as hypoesthesia, may be commonly encountered in TN patients and do not always require further investigation. A Danish study found that 29% of surgically naive TN patients exhibited sensory abnormalities, suggesting that these findings are a relatively typical aspect of the condition (35).

Differential diagnoses include postherpetic/posttraumatic or pain, trigeminal autonomic cephalalgias (TAC) (30,36). Glossopharyngeal neuralgia (GN) presents as stabbing pain in the back of the tongue, pharynx, or ear, which can be triggered by activities such as swallowing, coughing, and sneezing. In contrast, painful posttraumatic trigeminal neuropathy causes stabbing pain like TN but is preceded by a traumatic event and features distinct neurological abnormalities.

PIFP presents as aching, dull, constant pain, either spontaneous or touch evoked (16). Painful trigeminal neuropathy may be secondary to acute herpes zoster and presents as burning/stabbing pain after a herpetic rash in the trigeminal distribution. Other conditions, such as Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing (SUNCT), Short-lasting Unilateral Neuralgiform headache with Autonomic symptoms (SUNA), paroxysmal hemicrania, and cluster headache, cause stabbing pain accompanied by autonomic symptoms, with the notable difference that pain can shift sides, unlike in TN (33). Lastly, Primary stabbing headache is characterized by spontaneous, unilateral scalp pain, unaccompanied by autonomic symptoms. A cracked tooth presents as a shooting, sharp pain triggered by chewing hard foods. Cavities or pulpitis can lead to pain when consuming sweet/hot/cold foods. The pain can last anywhere from minutes to hours (30,36,37). Management of TN can be a challenge due to the chronicity, exacerbations, and nature of pain. The pharmacological management of TN involves antiepileptic drugs, muscle relaxants, and neuroleptic agents (36). Carbamazepine or oxcarbazepine is often recommended as the first-line medication. Gabapentinoids, lamotrigine, botulinum toxin type A, phenytoin, and baclofen can be used as monotherapy or in combination. Combined therapy with multiple drugs may be considered when monotherapy is ineffective (38). Vixotrigine, a Nav1.7-selective sodium channel blocker, is currently being investigated. Nav1.7, a key sodium channel in the nociceptive system, is absent in the brain, thereby mitigating the side effects associated with suppression of CNS excitability. This enables administration at therapeutic doses without the need for titration. Phase 3 trials were proposed in July 2020 and include two randomized, double-blind studies evaluating the safety and efficacy of lamotrigine compared with placebo in subjects with TN (39).

Surgical options can be explored in cases where there is inadequate pain relief or intolerable side effects (40). TN surgical management can be either ablative (destructive), where the sensory function of the trigeminal nerve is intentionally destroyed, or non-destructive, involving the decompression of the trigeminal nerve while preserving its normal function (40).

Microvascular decompression (MVD) has been regarded as the operative gold standard in classic TN since P. Jannetta described it (41), with the highest long-term satisfaction rate. However, due to the increased perioperative morbidity and mortality in older patients, MVD is often not offered as a primary choice (40). A systematic review evaluating the effectiveness of botulinum toxin in treating TN analyzed 4 studies and found that different dosages of botulinum toxin type A yielded similar outcomes, with no significant differences. Maximum efficacy was observed between 6 weeks and 3 months after the procedure. Side effects primarily included facial asymmetry after injection, headaches, and hematoma, all of which resolved in one week (41,42).

Idiopathic facial pain

• BMS (Glossodynia/Stomatodynia).
• PIDP and PIFP.

These two disorders are the most prevalent neuropathic conditions affecting the orofacial region. They are associated with a long history of inaccurate “myths” and dogmas about their nature. More than any other chronic orofacial pain conditions, patients with these disorders were most likely to be told that their pain is “psychogenic” or some manifestation of a mood disorder. While there is a higher degree of comorbid psychogenic conditions among these patients, the evidence is clear that they are not the cause of pain. If anything, they are a result of unrelieved pain and suffering (43).

BMS

BMS is a challenging condition to diagnose and treat. It is an intraoral burning sensation without clinical pathology (44,45). Depending on the classification system, BMS may be defined in several ways. Table 3 presents ICD-10 and ICD-11 descriptions of BMS. BMS often involves two-thirds of the anterior tongue but may also occur on the gingiva, lips, hard palate, and pharynx (44-46). As noted in the ICHD-3 criterion, BMS often presents bilaterally with variations in pain intensity (9). It occurs more commonly in women, specifically, those who are postmenopausal in their 50–60 years of life, and the prevalence increases with age (45,46). Bergdahl [1999] reported a prevalence of 12% in women in their fifth and sixth decades of life (47). The reported prevalence of BMS ranges from 0.7% to 15% among adults (47,48). Individuals with BMS often present with dysesthesia, xerostomia, and alterations in taste (44-46). Patients often describe a bitter or metallic taste (46). Up to 70% of patients with BMS report experiencing taste distortion, often perceived as a bitter or metallic change (45,46,49). Measurements of taste thresholds through whole-mouth tastings indicate elevated levels, resulting in decreased sensitivity to salty, sweet, sour, and bitter flavors, which creates difficulties in identification, particularly for salt and sour (50). Dysgeusia has been documented in about 70% of BMS patients (44,51). Forssell et al. [2012] reported that patients with BMS described the pain as ‘burning’, stinging’, pricking’, ‘throbbing’, and ‘troublesome’ (52). BMS pain typically increases throughout the day; nonetheless, patients rarely complain of it waking them from sleep (45, 0). Still, patients with BMS often have poor sleep quality (45). Pain may be exacerbated by stress, hot, spicy, or acidic foods or drinks (44,52). It varies from intermittent to constant and often occurs for periods without remission (44,45). The onset of BMS is often spontaneous but may occur secondary to procedures, stress, medications, or foods (44,45,52,53). Spontaneous remission within 5 years in BMS patients has been reported at 3% (54). Individuals with BMS are more likely to experience generalized anxiety disorder, major depressive disorder, and hypochondria, and often require more psychotropic medication compared to the general population. BMS is sometimes divided into primary and secondary BMS (55). Distinguishing between primary and secondary BMS is crucial for effective management. Primary BMS is an idiopathic condition with no underlying disease, and diagnosis is made by exclusion, as imaging, cytology, and clinical examinations will yield expected results. In contrast, secondary BMS is linked to an underlying condition and requires identifying and treating the root cause (53). Tissue trauma, infections, allergies, autoimmune conditions, gastrointestinal disease, thyroid disorders, hormonal deficiencies, parafunctional habits, xerostomia, nutritional deficiencies (vitamin B12 deficiency, iron, vitamin B complexes, and zinc), and medications, especially involving angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril), may elicit secondary BMS (55-57). Due to the numerous underlying conditions that can contribute to BMS, a comprehensive evaluation is necessary to determine the cause. BMS is the most prevalent NP disorder, affecting approximately 1% of the general population. Its prevalence increases with age, impacting nearly 6% of individuals over 70 years.

The pathogenesis of BMS is not well understood but is believed to be multifactorial (44,45,58). Despite comprehensive research investigating sex-related biomarkers, hormones, and genetics, no distinct differences have been found between men and women with BMS. Evidence supports BMS as a small-fiber (C-fiber) peripheral neuropathy (59). Despite effective treatments and guidelines for NP, many patients remain untreated or inadequately treated. Raising awareness of NPs among patients and healthcare providers is essential for enhancing treatment outcomes in chronic NP cases. Additionally, NOP encompasses various disorders affecting the mouth and face, underscoring the need for comprehensive management. He also reported increased transient receptor potential vanilloid channel type 1 (TRPV-1) in the tongue papillae (59). TRPV-1 is a nociceptive receptor. Nerve growth factor, which regulates TRPV-1, also increased in BMS patients (59).

Individuals with BMS exhibit abnormal sensitivity to temperature. Yet their mechanical sensation remains unaffected, indicating damage to only the small nerve fibers responsible for thermal sensation, while motor function, governed by larger nerve fibers, remains intact. Notably, studies have shown a significant reduction in both myelinated and unmyelinated nerve fibers in the tongues of BMS patients, particularly in areas where symptoms are most pronounced. An emerging mechanism, supported by multiple lines of investigation, proposes that trigeminal peripheral neuropathy is characterized by hyperexcitability due to disinhibition (60,61). Taste and sensory components will be reduced, which may be caused by chorda tympani damage and dysfunction. This dysfunction or damage may lead to a loss of central inhibition of the trigeminal nerve, resulting in hyperactivity (60,61). Taste afferents are reduced with age. Loss of taste afferents and inhibitory tone on somatosensory activity results in increased and abnormal activity in pain afferents (also supported by QST) (62).

BMS is proposed to be at least partially neuropathic, with increased expression of specific receptors and reduced nerve fibers (63). Among other theories postulated about pathogenesis, BMS may be related to dopamine deficiency. Prakash [2012] reported reduced BMS symptoms after administration of dopaminergic medication (64). Before treating BMS, it's essential to rule out all potential local and systemic factors. Managing primary BMS is particularly challenging because its cause is unknown. The primary goals of BMS treatment include patient education and reassurance, symptom relief, and psychological and social support as needed (44).

Treatment approaches vary and may include topical treatments, systemic medications, and cognitive-behavioral therapy (44). A stepwise treatment plan is often recommended, starting with a single topical treatment. If ineffective, systemic treatment is considered. Clonazepam, a benzodiazepine, is typically the first-line treatment. A single or combination treatment approach may be necessary to alleviate burning sensations and improve overall patient well-being. Clonazepam, a benzodiazepine, is often the first-line medication prescribed for BMS and has been reported to reduce BMS symptoms (63,65). Other treatment modalities, including anticonvulsants, tricyclic antidepressants (TCAs), and antioxidants, have limited or inconclusive reported efficacy (66). Topical medications are beneficial for patients with BMS, either as a complementary therapy or as primary treatment. One such medication is capsaicin, a compound derived from chili peppers, which alleviates pain by desensitizing pain receptors. It causes an initial increase in the burning sensation right after application (67). Laser therapy can be effective for patients with BMS, as it works by boosting serotonin and certain endorphins and depolarizing C-fibers (68). Alpha-lipoic acid (ALA) functions as a mitochondrial coenzyme and has antioxidant and neuroprotective properties. Research indicates that it may be beneficial for some patients with BMS (69). Despite advances in scientific understanding, BMS remains a poorly understood, underrecognized, and enigmatic condition characterized by pain. The varied and unpredictable symptoms of BMS pose a significant challenge for healthcare practitioners and can substantially impair patients' oral health-related quality of life.

PIFP and PIDP

PIDP and PIFP, previously known as atypical odontalgia, atypical facial pain, or phantom tooth pain, are chronic pain conditions that affect the face and dentoalveolar structures. Importantly, PIDP is regarded as a subset of PIFP. Initially described in 1924 by Franzier and Russell (70), who noted that 10-15% of patients with chronic facial pain had pain that differed from TN. They called these conditions atypical odontalgia (AO). For years, the terms AO and atypical facial pain were used to refer to intraoral and extraoral pain, respectively (71). The recent ICOP classification has introduced the terms PIDP and PIFP, providing more precise descriptions of these diagnoses (16). According to ICHD-3 and the International Headache Society (IHS), PIFP is defined as persistent facial and/or oral pain with variable presentations, occurring daily for more than 2 hours and lasting longer than 3 months, without any clinical neurological deficits (Table 4). The quality of the pain can range from sharp and shooting to dull and aching, and it does not follow a specific nerve distribution (12).

As PIDP and PIFP management strategies are similar, this article will focus on PIDP, which is more relevant to dentists. PIDP is a persistent pain condition localized to the dentoalveolar region, with no identifiable odontogenic, musculoskeletal, or psychological origin.

There are two possible subtypes:

• Primary, in which no apparent cause could be found.
• Secondary, which is linked to a causal event such as trauma.

ICOP addresses secondary dentoalveolar pain through the term post-traumatic trigeminal neuropathic pain (PTNP). PIDP is a rare pain disorder with an estimated prevalence of 0.03%, and the incidence is around 4.4 per 100,000 person-years (72,73). The clinical characteristics of PIDP include dull or sharp pain that is poorly localized, unilateral or bilateral, and intraoral, with a longer duration (16). In contrast, TN is characterized by well-defined pain confined to one branch of the Trigeminal nerve. The ICOP classification provides detailed definitions for PIFP and PIDP, as outlined in Table 3, and categorizes PIDP and PIFP based on the presence or absence of somatosensory changes.

Notably, many patients report that their pain began after a dental procedure, facial trauma, or other surgical interventions. Despite the normal healing period having passed, the pain persists. To alleviate their pain, these patients often undergo multiple invasive dental procedures, which, unfortunately, provide little to no relief and may even exacerbate the pain due to additional nerve damage. PIDP is a NP disorder that can occur even after a minor tissue injury and is often the type associated with minimally invasive dental treatment (74). It is usually related to therapeutic peripheral nerve injury during endodontic treatment or, less commonly, following extractions (75). While tooth extractions and endodontic treatments involve severing peripheral nerves that innervate the pulp, the resulting wound and injured nerve environments differ significantly. Following an extraction, the open socket allows injured nerve endings to survive and potentially reinnervate new targets as the socket heals. In contrast, endodontic treatment often leaves the amputated nerve in locally inflamed periapical tissues, where it is unable to reinnervate new pulpal targets due to the physical barrier created by the gutta-percha filling. While the prevalence of post-endodontic PIDP is estimated at 1–2% of cases, it is well established that around 5.3% of perfectly performed root canal procedures result in lingering/permanent localized NP (76).

Few studies examined the incidence and prevalence of PIDP in the general population. A retrospective study evaluating more than 3,000 patients in an orofacial pain specialty clinic between 2003 and 2007 reported a prevalence of 2.1 percent (77). However, a study conducted at an orofacial pain hospital-based center by Howard Israel et al. reported a 40% prevalence rate (78). Typically, patients with PIDP initially present with pain and undergo an average of seven consultations before receiving an accurate diagnosis. Unfortunately, PIDP is often misdiagnosed, as dentists tend to focus on identifying inflammatory signs and symptoms. To diagnose PIDP, all other potential causes of pain must be ruled out before referring the patient to a specialized clinic.

Despite limited research, particularly in animal models, the pathophysiology of PIDP remains unclear. However, PIDP is recognized as a type of NP characterized by abnormal sensations, including pain or hypersensitivity, perceived by the affected individual and originating from the peripheral or central nervous system. Current research suggests that deafferentation of the primary trigeminal nerve fibers occurs following alveolar trauma during dental procedures (79,80). Many studies indicate that both peripheral and central mechanisms are involved in initiating and maintaining PIDP. Studies in PIDP testing the ability of the patients to process trigeminal nociceptive information using QST (81) and blink reflex (82) have provided evidence suggesting abnormalities in peripheral perception of these patients, and peripheral input, in addition to central sensitization of higher order neurons may be involved in the pathogenesis of PIDP (83). The pain associated with idiopathic facial pain is often diffused and can even cross the midline, suggesting central sensitization. Interestingly, regional anesthesia administered at the site of pain is no more effective than a placebo (84).

Despite ongoing research, the underlying pathophysiology of idiopathic facial pain remains poorly understood. Studies have yielded conflicting results regarding the relationship between dental procedures and PIDP. While some studies report that dental procedures preceded 54–83% of PIDP cases, others indicate that 24–64% of cases had no prior dental work, underscoring the complexity of this condition. There is also recent evidence that suggests that PIFP is characteristically like trigeminal NP, presenting as different ends of a continuum (51,85). Masticatory myalgia has been reported in 50–55% of PIDP patients (86). Pain originating from the temporalis, masseter, and digastric muscles can radiate to the teeth. Interestingly, the pain may be localized to the teeth, while the muscles remain pain-free unless specifically palpated (87). Myofascial pain from these masticatory muscles can be misdiagnosed as PIDP if not properly examined. PIDP can manifest as constant pain with intermittent exacerbations, bearing some resemblance to classic TN, accompanied by persistent facial pain. Notably, TN attacks often follow a specific anatomical pattern aligned with the trigeminal nerve branch.

A patient's history of PIDP pain is a significant predictor of their likelihood of developing post-procedural NP in the future (88). While the exact pathophysiology of these disorders is not fully understood, some individuals are likely to have a genetic predisposition to an abnormal nervous system response to minor injuries, increasing their risk of developing NP (89). Millions of dental procedures are performed in the United States and worldwide, but very few result in PIDP (90). It is crucial to inform patients at risk of pathological outcomes about the potential for such outcomes and take proactive measures to minimize this risk. Research has identified the duration and intensity of preoperative and intraoperative pain as significant risk factors for developing PIDP. To mitigate this risk, achieving profound anesthesia during invasive procedures is essential. This helps reduce neuronal hyperexcitability, a key factor in the establishment of pathological neural plasticity and pain “memories” that can persist even after tissues have healed. There is some evidence that prophylaxis with an adjuvant analgesic medication for NP (selected anti-convulsant, tricyclic antidepressants) during the two to three weeks post-operative healing period can reduce the risk of developing NP (91). To optimize postoperative recovery, minimizing inflammation and primary hyperalgesia is crucial. In managing idiopathic facial pain, it's essential to recognize that there are no curative therapies available. Instead, treatment focuses on symptom management, with pharmacotherapy remaining the primary approach. Patient education and reassurance are vital, as individuals must understand that their pain is unrelated to dental issues. Reassure the patient and educate them that it is not of odontogenic origin. Pain should not be considered psychogenic, although psychological comorbidities like depression and anxiety are common in patients with PIDP (92). The severity of damage caused by misinterpreting PIDP as tooth-related pain should not be overlooked. To prevent further exacerbation of NP, unnecessary dental procedures should be avoided. Unfortunately, there is a lack of clinical studies on efficacious management strategies for idiopathic facial pain, resulting in limited evidence-based recommendations for PIDP treatment. However, TCAs have demonstrated efficacy in managing this condition. Studies by Sharav et al. (92) reported that high- and low-dose TCAs are effective in managing idiopathic facial pain.

The primary treatment for PIFP and PIDP continues to be low doses of TCAs, with Amitriptyline and Nortriptyline being the most frequently prescribed medications. Typical starting doses are 25–100 mg per day for Amitriptyline and 20–50 mg per day for Nortriptyline. If TCAs are contraindicated or ineffective, second-line options such as anticonvulsants, including Pregabalin, may be considered, as they have demonstrated efficacy in certain studies (93).

Topical medications targeting the area of pain have also been effective in the management of PIDP (94,95).

A few studies have examined the efficacy of botulinum toxin type A (BTxA) in the management of PIDP. They have shown that BTx A is effective (95). Effective management of TN and PIDP) involves a multifaceted approach. Botulinum toxin (BTx) alleviates NP by inhibiting the release of inflammatory mediators and deactivating sodium channels (96). A comprehensive strategy for PIDP includes educating patients about their pain, pharmacological interventions, and psychological interventions, with the primary objectives being pain reduction and rehabilitation. Additionally, invasive procedures such as exploratory surgery should be avoided, and irreversible treatments like root canal treatment or extraction should only be considered if clear pathology is evident, with non-invasive methods preferred for diagnostic purposes.

NOP conditions may mimic odontogenic pain. Acute odontogenic pain may be differentiated from NOP by comprehensive clinical examination and radiographic imaging. In odontogenic pain, local anesthetic infiltration/blockade relieves the pain completely, whereas in conditions such as PIDP/PIDF, local anesthetic is equivocal.

Strengths and limitations

At present, there are very few review articles focusing exclusively on NOP. In 2020, the most comprehensive classification of orofacial pain conditions, the ICOP, was published. There is a lack of review articles familiarizing healthcare professionals with NOP using ICOP criteria. The limitations of the review and future articles may include a lack of information on diagnostic tools and the differential diagnosis of NOP.

Conclusions and clinical implications

NOP is complex and may pose diagnostic challenges for dentists and healthcare providers.

Accurate diagnosis is the key to successful management. Familiarization with current

classification systems, diagnostic criteria, and updated terminologies may enable precise diagnosis and management. Further research in NOP should rely on using standard classification and diagnostic criteria. Early referral to orofacial pain specialists and multidisciplinary management may be required in complex cases. The potential role of this review may be enhanced in the future diagnosis and treatment of NOP.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Frontiers of Oral and Maxillofacial Medicine for the series “Orofacial Pain”. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://fomm.amegroups.com/article/view/10.21037/fomm-2025-1-50/rc

Peer Review File: Available at https://fomm.amegroups.com/article/view/10.21037/fomm-2025-1-50/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://fomm.amegroups.com/article/view/10.21037/fomm-2025-1-50/coif). The series “Orofacial Pain” was commissioned by the editorial office without any funding or sponsorship. J.K. serves as an unpaid editorial board member of Frontiers of Oral and Maxillofacial Medicine from June 2026 to December 2028 and served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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