Trigeminal neuropathies following dental anesthetic blocks: a review of the literature

Introduction

Trigeminal nerve injuries (TNI) represent possible complications associated with oral and maxillofacial procedures. The trigeminal nerve, the main cranial nerve responsible for sensory innervation of the face and oral cavity and control of masticatory muscles (1), is susceptible to damage during various dental interventions (2). While certain etiologies of TNI (e.g., nerve injuries derived from local anesthetics (LA) or third molar extractions) are mainly transient, those derived from implant placement and endodontic procedures tend to extend beyond the immediate post-injury period and become permanent (3,4). When the symptomatology lasts longer than 3 months, the International Classification of Orofacial Pain (ICOP) has proposed to name these conditions as post-traumatic trigeminal neuropathic pain (PTTNP). Specific diagnostic criteria will be discussed later in this review.

Establishing the prevalence of TNI is challenging and likely underreported in the existing literature. Estimates range between 0.5% and 5% among individuals undergoing oral and maxillofacial procedures (5-7), but the exact figures may vary according to the specific etiology of the nerve injury. Accurate diagnosis of these complications, characterized by persistent painful and non-painful somatosensory changes, often occurs approximately 1 year post-injury due to the complexities of diagnosis (5,8). This diagnostic delay and the resulting somatosensory changes adversely impact the patient’s quality of life and psychosocial health, mainly when the symptoms are painful (9-12). Understanding the factors contributing to persistent trigeminal nerve-related complaints is critical for promptly adopting effective therapeutic management and preventive strategies. This starts with a thorough and informed consent process that precisely communicates the potential benefits and risks of the intervention (2). Yet, the literature indicates that only 30% of patients who later developed posttraumatic neuropathy of the trigeminal nerve received informed consent (12,13). Likewise, many were not informed about the potential risk of TNI (12,14). A comprehensive understanding of the types of dental procedures, coupled with early and late therapeutic options for these injuries, is crucial. Immediate intervention is emphasized for a more favorable prognosis (8,15), with the chance of improvement decreasing by almost 6% each month that elapses from the injury (16). Early management is also suggested to minimize chronification risk and prevent central sensitization states (8).

This review offers an overview of TNI, summarizing dental procedures responsible for nerve injuries, specifically focusing on dental anesthetic injections. It delves into early and late management strategies, along with diagnostic criteria for accurate diagnosis. By offering this comprehensive exploration, the review not only aims to educate about potential TNI but also informs clinicians of the importance of early management and prompt referral to minimize complications, ultimately enhancing patient care in dental practice. We present this article in accordance with the Narrative Review reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-24-5/rc).

Methods

The current study comprises a comprehensive literature review conducted on PubMed, Google Scholar, Scopus, Ovid, and Web of Science, searching for English-language articles discussing injuries to the trigeminal nerve from dental procedures in human patients, regardless of the study design. Special attention was directed toward TNI associated with injections. As proposed in a previously published systematic review (17), the search strategy employed terms identifying injuries to the V2 and V3 branches of the trigeminal nerve [specifically the inferior alveolar nerve (IAN), the lingual nerve, or the maxillary nerve], such as “trigeminal nerve injuries” OR “posttraumatic neuropathy of trigeminal nerve” OR “posttraumatic trigeminal neuropathic pain” OR “altered sensation” OR “paresthesia” OR “allodynia” OR “neurosensory disturbance” OR “dysaesthesia”. These search terms were combined with those referring to dental procedures, specifically LA (e.g., “local anesthesia” OR “mandibular block analgesia” OR “mandibular injection” OR “dental injection” OR “inferior alveolar nerve block”) and diagnostic criteria (including terms such as “assessment”, OR “evaluation”, OR “diagnosis”). The last search was performed on the 19^th of February 2024. Table 1 summarizes the search strategy of the present narrative review.

Classification of TNI

Various classifications have been proposed in the literature to categorize nerve injuries (18-23) and, by extension, predict the likelihood of recovery (Table 2) (24). The International Association for the Study of Pain (IASP) proposed a classification of chronic pain for the International Classification of Diseases, 11th revision (ICD-11); specifically, in its chronic neuropathic pain section, diagnostic criteria for painful neuropathic pain are described (25). It was suggested that suspected diagnosis of neuropathic pain requires specific investigations to ascertain that the pain originates in the nervous system, and that the distribution of pain should correspond to the underlying lesion or disease of the somatosensory nervous system (25). The neuroanatomical connection to the root cause should remain identifiable even if pain is not experienced throughout the entire area supplied by an affected peripheral nerve or nerve root. This also applies to the mapped representation of a lesion or illness in the central nervous system, or if the pain extends beyond these boundaries (25). Detectable objective signs of a sensory disorder within the pain’s distribution enhance diagnostic certainty. These signs may suggest a sensory impairment or exaggerated responses to typically painful (hyperalgesia) or non-painful stimuli (allodynia).

Descriptors of neurosensory disturbances as described by IASP are reported in Figure 1. Notably, the motor component remains unaffected, branching out before entering the IAN foramen.

Figure 1 Descriptors of neurosensory disturbances, according to the International Association for the Study of Pain.

Dental procedures associated with TNI

Within the field of dentistry, numerous procedures can potentially cause TNI, including LA, root canal treatments, tooth extractions, implants, and orthognathic surgery (Table 3). Interestingly, the intensity of pain and neurosensory impairment does not necessarily correlate to the invasiveness of the dental procedure, so much so that a straightforward procedure may lead to more post-operative pain than a more invasive one. This review will specifically discuss TNI originating from the administration of local dental anesthesia.

Risk factors

Several common risk factors associated with the development of TNI following dental procedures are attributed to the specific procedure, the provider, and the patient.

Inherent risk factors specific to the surgical dental procedure are outlined in Table 3. Overall, a thorough pre-operative assessment, including radiographs or cone beam computed tomography (CBCT), is crucial to minimize the risk of encountering unexpected anatomical variations.

Moreover, the experience of the dental provider has been suggested as a significant factor influencing the risk of TNI occurrence (26).

Patients with specific characteristics are more prone to developing posttraumatic neurosensory changes, including those with existing neuropathic pain (27), chronic widespread pain (i.e., fibromyalgia), heightened psychological distress (pain catastrophizing, anxiety, depression, fear avoidance, somatization, levels of physical activity, self-efficacy, neuroticism), older age (>50 years old), female gender, a pre-existing migraine condition (14), and pre-operative moderate-severe neuropathic pain (3,28,29). Vulnerable patients often exhibit impaired diffuse noxious inhibitory control. Specific genetic variants associated with mitochondrial phosphate carriers and calcium binding genes in the brain and dorsal root ganglia, such as SLC25A3 at chromosome 12q23.1 [odds ratio (OR) =1.68, 95% confidence interval (CI): 1.40–2.02] and at 13q14.2 near CAB39L (OR =1.09, 95% CI: 1.05–1.14), have been identified to increase susceptibility to neuropathic pain (30). While studies have correlated genetic variants of COMT, OPRM1, TNFA, HLA, GCH1, and IL6 with an increased predisposition to neuropathic pain (31), particularly painful diabetic neuropathy, they have not precisely targeted injuries of the trigeminal nerve.

Diagnostic tests for identification of pre-existing neuropathic conditions

In cases where patients present with existing neuropathic pain at baseline, opting to avoid elective surgery is the recommended choice. Preoperative screening of patients can be conducted using validated diagnostic tools (32), including the following tests:

• Neuropathic Pain Questionnaire (NPQ), a 12-item questionnaire (ten sensory and two affect items) containing descriptors of neuropathic pain (33), or its short-form (NPQ-SF), where the 0–100 pain scale is combined with discriminant function coefficients of tingling, numbness, and increased pain to touch (34). A cut-off of ≥0 is used to establish the presence of neuropathic pain (34).
• Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) consists of five items investigating sensory symptoms and two items on sensory clinical examination (35). Its modified self-reported version (S-LANSS) allows neuropathic pain screening without relying on clinical assessment (36). A cut-off of ≥12 suggests neuropathic pain (35).
• Douleur Neuropathique en 4 (DN4) is a 10-item questionnaire based on seven sensory symptom descriptors and three signs of clinical examination (37). A cut-off of ≥4 distinguishes neuropathic from non-neuropathic pain (37).
• PainDETECT is a self-reported questionnaire composed of seven sensory descriptive items and two spatial and temporal pain items (38). A cut-off of ≥19 suggests a neuropathic pain component (38).
• ID-Pain, a 6-item questionnaire comprising five sensory descriptors and one nociceptive pain item related to the joints (39).

All the above questionnaires can also be employed to monitor the progression of neuropathic and somatosensory changes during follow-up.

Despite being validated screening tools for overall neuropathic pain, their sensitivity and specificity are considered low when applied to the screening of trigeminal neuropathies (40-42), as they lack specificity for the orofacial region. Conversely, a more specific screening questionnaire has been developed to assist general dentists in the differential diagnosis of neuropathic pain derived from dental procedures from other types of orofacial pain, such as trigeminal neuralgia, acute odontogenic pain, and temporomandibular disorders (43). This questionnaire is a 10-item instrument that has been proven to exhibit a sensitivity of 77% and a specificity of 69% (43). Other questionnaires have been designed to monitor treatment response, such as the Neuropathic Pain Scale (44).

Diagnostic tests for identification and quantification of neuropathic conditions

Clinical diagnostic tests compare the affected with the unaffected side to examine the presence, extension, and severity of neurosensory disturbances (for a detailed review, refer to (17). These include the following:

• Clinical neurosensory tests consist of noninvasive chairside tests which inspect the sensory components of the trigeminal nerve. These include static 2-point discrimination, dynamic 2-point discrimination, sharp-blunt discrimination, pinprick sensation, light touch, and thermal warm/cold differentiation (17). These sensory modalities can be tested utilizing unexpensive tools, such as cotton wisp, Q-tip, pressure gauge, or blunt tip (45,46), or more sophisticated instruments, such as von Frey or Semmes Weinstein monofilaments (47,48).
• Thermal quantitative sensory testing (QST) measures the thermal (cold or heat) detection threshold, pain threshold and tolerance to the application of a thermode of different size, frequency of stimuli, rate of ascending/descending temperature on the affected area (17). Thermal thresholds mainly test the function of thinly unmyelinated C-fibers and polymodal nociceptors; Aδ fibers and peripheral nerve afferents can also be involved (49).
• Electrical QST quantifies the electrical detection thresholds by applying an electrode to the nerve distribution. It tests the function of thickly myelinated Aβ fibers (50).
• Neurophysiological techniques include nerve conduction studies, measure of somatosensory-evoked potentials, laser-evoked potentials, contact-heat-evoked potentials, and trigeminal blink reflexes (51). Neurophysiological tools mainly test large non-nociceptive Aβ fibers as well as small nociceptive afferent fibers (51).
• Electromyography can be utilized as a measure of severity of nerve injury, by comparing amplitude and latency of sensory action potentials provoked by electrical stimuli (48).

Clinical diagnostic tests can also be utilized to monitor symptoms evolution over time.

Injection-related TNI

The administration of LA is generally deemed safe in healthy individuals. Nevertheless, although rare, documented cases in the literature report injection-related TNI, particularly affecting the inferior alveolar and lingual nerves. A distinctive aspect of dental practice is that, in contrast to other medical specialties, dental providers actively target the nerve during local anesthesia (LA) administration rather than avoiding direct contact (2). Although the exact mechanism is still debated, neurosensory disturbances are proposed to derive from intraneural hematoma formation leading to scar and reactive fibrosis (52-57), direct trauma caused by the beveled barbed needle (56,57), and neurotoxicity resulting from intrafascicular injection or needle withdrawal (57-60). The neurotoxicity is attributed to the presence of alcohols or sterilizing agents in the anesthetic solution or on the needle itself (57) or the release of reactive free radicals in response to the ischemia induced by edema (61). Irrespective of the exact mechanism, sensory disturbances may arise from the disruption of neural transmission.

Incidence

The incidence of injection-related TNI ranges from approximately 1 in 14,000 to 1 in 13,800,970 cases per injection (14,53,54,60,62-64). Their occurrence is more pronounced when associated with oral surgery procedures, with incidence rates reported as 1 in every 3,300 local injections. Nevertheless, this estimate is likely underestimated due to the high number of unreported cases in private practice. It has been proposed that each actively practicing provider may encounter 4 to 6 temporary and one permanent TNI during their career (2).

Risk factors

Certain anesthetics are more commonly associated with injection-related TNI, including articaine 4%, lidocaine 2%, mepivacaine 3%, and prilocaine 3% (53,63,65-70). Notably, it is suggested that a 4% formulation is more frequently associated with TNI than the type of anesthetic itself (54,58,62). Particularly in cases involving the lingual nerve, patients are more likely to receive multiple injections and may report pain or an electric shock sensation during the injection procedure (53,57,71). Nevertheless, even though indicative of direct needle contact with the nerve trunk (72), an electric shock sensation occurs in 1.3–8% of all mandibular anesthetic blocks and is not always associated with TNI (53,55,57,73-75). However, clinicians are advised to document instances when patients report an electric shock sensation during anesthesia administration (2).

The lingual nerve appears to be more frequently associated with neurosensory disturbances than the IAN following a mandibular block (58,59); and the incidence of injection-related TNI seems higher in females (76).

Prevention

There are, to date, no established means of preventing injection-related TNI, partly due to a lack of understanding of the etiological mechanism (53,57). Some studies have proposed favoring buccal infiltration and avoiding anesthetic blocks when feasible (71,77). It has also been suggested to avoid 4% formulation when possible (44,48,52).

Clinical manifestation

Injection-related TNI primarily present as anesthesia, hypoesthesia, hyperalgesia, taste alteration, dysesthesia, allodynia, and burning pain (71,72,78), predominantly affecting the lingual nerve (14,79). The unifascicular nature of the lingual nerve, as opposed to the multifascicular IAN, has been suggested as a potential reason (79), along with its thicker perineurium, which may result in greater endoneurial pressure and the inclusion of all axons in the event of haemorrhage (80).

Functional interference

Patients experiencing injection-related TNI may express difficulties with eating, drinking, speaking, and social interaction (71). Sleep disturbance and mechanical allodynia have also been reported during activities such as shaving and make-up application (71).

Prognosis

Neurosensory disturbances of TNI derived from LA are anticipated to resolve within 8 weeks in 85–94% of the cases (14,53,57), although other studies indicate a poorer prognosis (55,59), with approximately 25–29% of these injuries being permanent (14,64). Injuries associated with the lingual nerve are more likely to be permanent, possibly due to the higher mobility of the nerve, the lower number of fascicles compared to the IAN, and the absence of protection provided by a bony canal (53,59,71,76).

Early management of TNI

Figure 2 depicts a flowchart outlining the early management of TNI (3,81), regardless of their etiology. The diagram underscores the importance of prompt identification, intervention, and pharmacological management. If nerve damage is evident, a range of micro-surgical interventions (e.g., guided nerve regeneration, redirection to a different anatomic location, nerve capping, graft, neurectomy, internal neurolysis, etc.) is advisable. Conversely, in cases where nerve damage is not suspected, clarification of normal post-operative expectations should be provided, and regular follow-up maintained, whether or not a nerve intervention procedure was performed or nerve damage was suspected. Specifically, if an electric shock sensation is reported during local infiltration, initial steps involve monitoring and reassuring the patient the following day. If altered sensation or abnormal pain persists after the dental procedure, a detailed history, clinical examination, and assessment of somatosensory changes should be conducted. A combination of numbness, altered sensation, pain, or taste alterations raises concerns and requires further evaluation. Clinical examination involves mapping the affected dermatome area for initial assessment and monitoring of disease progression in future follow-ups. Comparison with the unaffected side should assess responses to light touch, sharp, blunt discrimination, two-point discrimination, and thermal sensation (3).

Figure 2 Flowchart of early management of trigeminal nerve injuries. Flowchart created based on recommendations published by Renton and van der Cruyssen (3), Neal and Zuniga (29), and Zuniga and Renton (81). MRI, magnetic resonance image; TNI, trigeminal nerve injuries.

In confirmed cases of TNI, early management and intervention depend on the duration and etiology of TNI, ranging from implant removal to addressing endodontic overfilling. On the contrary, injection-related TNI is typically managed pharmacologically (3), with no recommended surgical intervention for such cases (14). Early management involves a high dosage of non-steroidal anti-inflammatory drugs (400–800 mg oral ibuprofen, four times/day or ibuprofen + paracetamol), oral prednisolone for gradual tapering, and a vitamin B complex (i.e., riboflavin 400 mg once daily + other vitamin B for max 90 days) (Table 4) (2). Referral to the orofacial pain specialist is also advised.

Late-phase pharmacological management is indicated when somatosensory changes persist, primarily involving neuropathic pain medications, as further explained below.

Prognosis

Predictive factors for long-term (i.e., >6 months) persistence of somatosensory disturbance include sex (females > males, OR =2.23), older age (OR =1.03), higher number of painful comorbidities (OR =26.20), maxillary nerve lesions (OR =3.05), presence of thermal (OR =5.10) and mechanical hyperesthesia (OR =2.10), initiating events identified by endodontic treatment (OR =1.07) and implant placement (OR =1.86), and higher pain scores (OR =3.39) (4). In addition, more proximal lesions to the cell body typically display a poorer prognosis (2). Conversely, the higher chance of recovery was related to etiology associated to the administration of LA (OR =0.08) and third molar surgery (OR =0.36) (4).

PTTNP

When the somatosensory changes persist after the immediate post-injury period and extend beyond 3 months, various organizations have proposed different terminologies to define this entity (Figure 3). This condition falls within the broader umbrella of neuropathic pain, defined by the IASP as “pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system” (32). Adhering to the latest classification (ICOP), these disorders are categorized as PTTNP, defined as unilateral/bilateral facial or oral pain resulting from trigeminal nerve trauma accompanied by clinical signs and/or symptoms of trigeminal nerve dysfunction persisting for more than 3 months.

Figure 3 Definitions provided by different organizations over time. IASP, International Association for the Study of Pain; ICHD, International Classification of Headache Disorders; ICOP, International Classification of Orofacial Pain.

Pain should manifest within the distribution of the affected nerve within 6 months of the injury. A history of TNI (i.e., mechanical, chemical, thermal, or radiation) should be reported, and diagnostic tests should be used to confirm the nerve lesion. Additionally, associated somatosensory signs and/or symptoms should be observed within the same nerve distribution. The pain, which is neuropathic in nature and is often described as stabbing and/or burning (11,82), rarely crosses the midline (83). Notably, the diagnostic criteria require a minimum of 3 months of persistent pain before a diagnosis is provided.

Derived from the framework of neuropathic pain affecting other body parts (84), PTTNP should be classified as possible when supported solely by the patient’s history; probable when supported by both history and clinical examination [QST and bedside qualitative sensory testing (QualST)]; and definite, when diagnostic testing confirms the condition (83,85). A recently published consensus guideline on TNI has underscored the importance of QualST in achieving an accurate diagnosis of TNI, whereas QST is recommended for cases where QualST results are inconsistent (8). Available diagnostic tests to confirm the diagnosis include imaging (i.e., magnetic resonance neurography, functional magnetic resonance imaging, diffusion tensor imaging studies) (86); surgical exploration of lesion or compression; neurophysiologic diagnostic tests such as laser-evoked potentials, contact heat-evoked potentials, blink reflex, corneal confocal microscopy, nerve conduction study; skin biopsy confirming reduced nerve fiber terminals (32).

Management of PTTNP

Table 4 summarizes the most established therapeutical options for late management of PTTNP (>6 weeks).

In most cases of PTTNP, where the likelihood of achieving a cure is minimal, a palliative strategy based on the recommendations for addressing peripheral neuropathic pain conditions may be employed. There is a lack of randomized clinical trials involving thoroughly characterized patients with PTTNP, and most recommendations apply to neuropathic pain in general (6,87,88).

For systemic management of PTTNP, tricyclic antidepressants (TCA), serotonin-noradrenaline reuptake inhibitor antidepressants, especially duloxetine, gabapentinoids (i.e., pregabalin, gabapentin, gabapentin extended-release), and enacarbil are strongly recommended as first-line treatments for neuropathic pain and supported by moderate to high-quality evidence (87). To improve efficacy and reduce adverse effects, a combination of pregabalin or gabapentin with duloxetine or TCA may be suggested (89).

Drug selection is contingent upon patient-related factors, including the presence of systemic comorbidities, age, and drug adverse effect profile (90,91). For example, systemic medications pose numerous challenges, particularly for elderly patients, those with systemic conditions, and individuals taking multiple drugs, as potential interactions and adverse effects may compromise treatment adherence (92,93). In these instances, a topical approach may be considered either independently or in conjunction with systemic medications (94).

For extraoral persistent PTTNP, topical administration of LA or capsaicin may be utilized, provided that any contact with the eyes is avoided. LA and capsaicin patches are commercially available and may offer greater comfort during application. Despite the successful application of 8% capsaicin patch for conditions such as trigeminal neuropathy, its use on the face is not approved due to its very high concentration and its proximity to mucous membranes (i.e., eyes and oral cavity).

Intraorally, certain areas may also be suitable for topical treatments, with the aid of a customized soft splint designed to cover the affected regions, frequently termed as “neurostent”. This neurostent allows for the application of LA, capsaicin alone or in combination under occlusion, minimizing the risk of the compounds spreading to other parts of the oral cavity and/or pharynx. Currently, there are no official recommendations regarding the concentrations of LA or capsaicin for intraoral use; however, a concentration of 0.1% capsaicin is likely the maximum tolerable to prevent excessive discomfort during application. For LA, commercially available lidocaine or benzocaine gels or creams can be utilized (6). Topical compounded medications, such as TCA, anticonvulsants, or a combination thereof, may be employed in some instances. Nonetheless, insufficient data is available regarding the safety and effectiveness of utilizing these medications via topical application (95).

Conclusions

TNI derived from dental procedures represent a potential consequence that patients should be informed about during the consent process. Although a relatively rare instance, injuries resulting from anesthetic injections are documented in the literature and merit attention and understanding from dental practitioners, especially considering the widespread use of LA during dental procedures. While around 75% of injection-related injuries exhibit spontaneous recovery within the initial weeks, a notable proportion leads to persistent somatosensory changes, negatively impacting patients’ quality of life. Strategies to mitigate the risk of injection-related TNI are outlined, advocating for practices such as avoiding anesthetic blocks, minimizing anesthetic concentration, and limiting multiple injections. Early identification and management of TNI are essential, as timely intervention substantially enhances prognosis. Predictive factors associated with patients, procedures, and providers are identified to aid clinicians in careful treatment planning, facilitating informed patient discussions about potential risks, and minimizing legal ramifications. In cases where chronic PTTNP persists, appropriate management necessitates referral and long-term use of neuropathic pain medications.

Acknowledgments

Funding: None.

Footnote

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