Infraorbital canal variants and its clinical and surgical implications. A systematic review.

BACKGROUND: Recent literature highlights anomalous cranial nerves in the sinonasal region, notably in the sphenoid and maxillary sinuses, linked to anatomical factors. However, data on the suspended infraorbital canal (IOC) variant is scarce in cross-sectional imaging. Anatomical variations in the sphenoid sinuses, including optic, maxillary, and vidian nerves, raise interest among specialists involved in advanced sinonasal procedures. The infraorbital nerve's (ION) course along the orbital floor and its abnormal positioning within the orbital and maxillary sinus region pose risks of iatrogenic complications. A comprehensive radiological assessment is crucial before sinonasal surgeries. Cone-beam computed tomography (CBCT) is preferred for its spatial resolution and reduced radiation exposure. OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants of the infraorbital canal (IOC) and report its association with clinical condition or surgical implication. METHODS: We searched Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to June 2023. Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Preliminary results show that three types are prevalent, type 1: the IOC does not bulge into the maxillary sinus (MS); therefore, the infraorbital foramen through the anterior wall of MS could be used for identification of the ION. Type 2: the IOC divided the orbital floor into medial and lateral aspects. Type 3: the IOC hangs in the MS and the entire orbital floor lying above the IOC. From which the clinical implications where mainly surgical, in type 1 the infraorbital foramen through the anterior wall of MS could be used for identification of the ION, while in type 2, since the lateral orbital floor could not be directly accessed an inferiorly transposition of ION is helpful to expose the lateral orbital wall directly with a 0 scope; or using angled endoscopes and instruments, however, the authors opinion is that direct exposure potentially facilitates the visualization and management in complex situations such as residual or recurrent mass, foreign body, and fracture located at the lateral aspect of the canal. Lastly, in type 3, the ION it's easily exposed with a 0° scope. CONCLUSIONS: This systematic review identified four IOC variants: Type 1, within or below the MS roof; Type 2, partially protruding into the sinus; Type 3, fully protruding into the sinus or suspended from the roof; and Type 4, in the orbital floor. Clinical recommendations aim to prevent nerve injuries and enhance preoperative assessments. However, the lack of consistent statistical methods limits robust associations between IOC variants and clinical outcomes. Data heterogeneity and the absence of standardized reporting impede meta-analysis. Future research should prioritize detailed reporting, objective measurements, and statistical approaches for a comprehensive understanding of IOC variants and their clinical implications. Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/UGYFZ .

Sex differences in carbamazepine effects in a rat model of trigeminal neuropathic pain.

Carbamazepine (CBZ) represents the first-line treatment for trigeminal neuralgia, a condition of facial pain that affects mainly women. The chronic constriction of the infraorbital nerve (CCI-ION) is a widely used model to study this condition, but most studies do not include females. Thus, this study aimed to characterize sensory and affective changes in female rats after CCI-ION and compare the effect of CBZ in both sexes. Mechanical allodynia was assessed 15 days after CCI-ION surgery in rats treated with CBZ (10 and 30 mg/kg, i.p.) or vehicle, together with the open-field test. Independent groups were tested on the Conditioned Place Preference (CPP) paradigm and ultrasonic vocalization (USV) analysis. Blood samples were collected for dosage of the main CBZ metabolite. CBZ at 30 mg/kg impaired locomotion of CCI-ION male and sham and CCI-ION female rats and resulted in significantly higher plasma concentrations of 10-11-EPX-CBZ in the latter. Only male CCI-ION rats showed increased facial grooming which was significantly reduced by CBZ at 10 mg/kg. CBZ at 10 mg/kg significantly reduced mechanical allodynia and induced CPP only in female CCI-ION rats. Also, female CCI-ION showed reduced emission of appetitive USV but did not show anxiety-like behavior. In conclusion, male and female CCI-ION rats presented differences in the expression of the affective-motivational pain component and CBZ was more effective in females than males. Further studies using both sexes in trigeminal neuropathic pain models are warranted for a better understanding of potential differences in the pathophysiological mechanisms and efficacy of pharmacological treatments.

Standardized Centella asiatica extract ECa 233 alleviates pain hypersensitivity by modulating P2X3 in trigeminal neuropathic pain

Abstract During oral surgery and temporomandibular joint repositioning, pain hypersensitivity often occurs due to irritation or inflammation of the nerve endings in the orofacial region. Objective: This study aimed to investigate the effects of ECa 233, a Centella asiatica-standardized extract, on the development of mechanical hyperalgesia and allodynia induced by chronic constriction injury of the infraorbital nerve in mice. Methodology: The right infraorbital nerves of the mice were ligated. Oral carbamazepine (20 mg/kg) or ECa 233 (30, 100, or 300 mg/kg) was administered daily for 21 days. Von Frey and air-puff tests were performed on both sides of the whisker pad on days 0, 7, 14, and 21. Thereafter, the expression of purinergic receptor subtype 3 (P2X3) and voltage-gated sodium channel 1.7 (NaV1.7), a transmembrane protein, in the trigeminal ganglion and c-fos immunoreactivity-positive neurons in the trigeminal nucleus caudalis was assessed. Results: After 21 days of infraorbital nerve ligation, the mice showed allodynia- and hyperalgesia-like behavior, P2X3 and NaV1.7 were upregulated in the trigeminal ganglion, and nociceptive activity increased in the trigeminal nucleus caudalis. However, the oral administration of carbamazepine (20 mg/kg), ECa 233 (100 mg/kg), or ECa 233 (300 mg/kg) mitigated these effects. Nevertheless, ECa 233 failed to affect NaV1.7 protein expression. Conclusion: Carbamazepine and ECa 233 can prevent pain hypersensitivity in mice. Considering the side effects of the long-term use of carbamazepine, ECa 233 monotherapy or combined ECa 233 and carbamazepine therapy can be used as an alternative for regulating the development of hypersensitivity in trigeminal pain. However, further detailed clinical studies should be conducted to provide comprehensive information on the use of ECa 233.

Morphometry of the infraorbital foramen in dentate and edentulous adult humans and its clinical relevance

The infraorbital foramen (IOF) serves as an important anatomical reference for infraorbital nerve block during different procedures. Its clinical and surgical relevance, associated with conflicting results in its anatomy description justifies the present study. Thus, this work aims to describe the IOF, qualitatively and quantitatively, and propose an accurate measurement to define its location. One hundred and seventy-four IOFs of dry skulls were analyzed and divided in dentate (DE) and edentulous (ED) groups. Distances were measured between the IOF and the margin of the alveolar arch of the maxilla (MAAM), the inferior orbital margin (IOM), the intermaxillary suture (IMS), the vertical plane of IOF. A new methodology was proposed to optimize the identification of IOF based on the IMS distance. Oval-shaped IOFs (n=81/174) with inferomedial orientation (n=104/174) and with a crest-shaped upper margin (n=163/174) constituted the norm for this sample. Distance between IOF and MAAM was 29.97 ± 4.09 mm, to IOM 7.27 ± 1.8 mm, and to IMS 35.09 ± 3.77 mm. ED individuals had IOF closer to MAAM (p=0.0124). The highest point of this methodology was the lack of statistical differences in the IMS distance in ED and DE specimens, making this method applicable for both. Therefore, to minimize iatrogenic injuries, clinicians and surgeons must consider the total or partial presence of teeth, the methodology established to find the IOF, its inferomedial orientation, and the prevalent crest on its superior margin.

Maresin-2 inhibits inflammatory and neuropathic trigeminal pain and reduces neuronal activation in the trigeminal ganglion.

Pain is a common symptom associated with disorders involving the orofacial structures. Most acute orofacial painful conditions are easily recognized, but the pharmacological treatment may be limited by the adverse events of current available drugs and/or patients' characteristics. In addition, chronic orofacial pain conditions represent clinical challenges both, in terms of diagnostic and treatment. There is growing evidence that specialized pro-resolution lipid mediators (SPMs) present potent analgesic effects, in addition to their well characterized role in the resolution of inflammation. Maresins (MaR-1 and MaR-2) were the last described members of this family, and MaR-2 analgesic action has not yet been reported. Herein the effect of MaR-2 in different orofacial pain models was investigated. MaR-2 (1 or 10 ng) was always delivered via medullary subarachnoid injection, which corresponds to the intrathecal treatment. A single injection of MaR-2 caused a significant reduction of phases I and II of the orofacial formalin test in rats. Repeated injections of MaR-2 prevented the development of facial heat and mechanical hyperalgesia in a model of post-operative pain in rats. In a model of trigeminal neuropathic pain (CCI-ION), repeated MaR-2 injections reversed facial heat and mechanical hyperalgesia in rats and mice. CCI-ION increased c-Fos positive neurons and CGRP+ activated (nuclear pNFkB) neurons in the trigeminal ganglion (TG), which were restored to sham levels by MaR-2 repeated treatment. In conclusion, MaR-2 showed potent and long-lasting analgesic effects in inflammatory and neuropathic pain of orofacial origin and the inhibition of CGRP-positive neurons in the TG may account for MaR-2 action.

Morphometric analysis of infraorbital foramen using cone beam computed tomography in a cohort of Sri Lankan adults / Análisis morfométrico del foramen infraorbitario mediante tomografía computarizada de haz cónico en una cohorte de adultos de Sri Lanka

SUMMARY: Infraorbital foramen (IOF) located bilaterally within the maxillary bone about 1 cm inferior to the infraorbital margin is a vital landmark when delivering local anesthesia and during surgical interventions in the midface region. A total of 122 infraorbital foramina in 61 cone beam computed tomographic (CBCT) images of 32 females and 29 males in the age range of 17 to 32 were analyzed to determine the shape, direction, presence of accessory foramina, size and the precise position of IOF in relation to the inferior orbital margin (IOM), maxillary midline (MM), lateral nasal wall (LNW), alveolus (ALV) and maxillary teeth in a group of Sri Lankan people. The IOF was oval in shape (80.3 % and 88.5 % on the right and left side, respectively) in a majority of individuals. The infraorbital foramina were located at a mean distance of 5.56 ± 3.95 and 4.91 ± 2.08 mm, below the IOM on the right and left side, 27.13 ± 2.6 and 26.99 ± 2.73 on the right and left side from the mid maxillary line, 11.96 ± 3.45 mm and 12.18 ± 3.35 from the LNW on the right and left side and 29.59 ± 3.59 and 29.65 ± 3.28 above the alveolar crest on the right and left side. There were no statistically significant differences between the left and right sides or between sexes. Majority of IOF (37.5 % and 55.9 % on the right and left side, respectively) were located in the vertical plane passing though the maxillary second premolar tooth.

RESUMEN: El foramen infraorbitario (FIO) ubicado bilateralmente dentro de la maxila, aproximadamente 1 cm inferior al margen infraorbitario, es un punto de referencia vital cuando se administra anestesia local y durante intervenciones quirúrgicas en la región media de la cara. Se analizaron un total de 122 forámenes infraorbitarios en 61 imágenes de tomografía computarizada de haz cónico (CBCT) de 32 mujeres y 29 hombres en un rango etario de 17 a 32 años para determinar la forma, dirección, presencia de forámenes accesorios, tamaño y posición precisa de FIO en relación con el mar- gen orbitario inferior (MOI), la línea mediana maxilar (MM), la pared nasal lateral (PNL), el alvéolo (ALV) y los dientes maxilares en un grupo de personas de Sri Lanka. En la mayoría de los adultos se observó que el FIO tenía forma ovalada (80,3 % y 88,5 % en el lado derecho e izquierdo, respectivamente) Los forámenes infraorbitarios se ubicaron a una distancia media de 5,56 ± 3,95 y 4,91 ± 2,08 mm, por debajo del MOI en los lados derecho e izquierdo; 27,13 ± 2,6 y 26,99 ± 2,73 en el lado derecho e izquierdo desde la línea maxilar mediana, 11,96 ± 3,45 mm y 12,18 ± 3,35 de la PNL en el lado derecho e izquierdo y 29,59 ± 3,59 y 29,65 ± 3,28 por encima de la cresta alveolar en los lados derecho e izquierdo. No hubo diferencias estadísticamente significativas entre los lados izquierdo y derecho o entre sexos. La mayoría de IOF (37,5 % y 55,9 % en el lado derecho e izquierdo, respectivamente) se ubicaron en el plano vertical que pasa por el segundo premolar maxilar.

Correlation analysis of infraorbital foramen with related anatomical structures / Análisis de correlación del foramen infraorbitario con estructuras anatómicas relacionadas

The anatomical localization of foramen infraorbitale (FOI) and its relationship with ambient structures are of great importance for clinicians and surgeons. This study was performed on seventy five skulls, and the distance between FOI to important anatomical formations, angular position of the zygomatic bone and the relationship between these parameters were investigated on both sides. The distance of FOI to margo infraorbitalis (MI), apertura piriformis (AP) and spina nasalis anterior (SNA), upper face height (UH) and upper face width (UW) were measured. Zygomatic bone triangle angles (SA, PA, IA) and porion-nasion-spina nasalis anterior angle (PNS) were measured from lateral view of the skull. While there was no significant difference between right and left measurement except for PA (p=0.03), the distance from FOI to MI is showed a very high degree positive correlation between the right and left sides, the distance from the FOI to AP was weak correlated only right side.

La localización anatómica del foramen infraorbitario (FIO) y su relación con las estructuras adyacentes son de gran importancia para los médicos y cirujanos. Este estudio se realizó en setenta y cinco cráneos, y se investigó la distancia entre FIO a formaciones anatómicas importantes, la posición angular del hueso cigomático y la relación entre estos parámetros en ambos lados. Se midió la distancia de FIO al margen infraorbitario (MI), apertura piriforme (AP) y espina nasal anterior (ENA), altura superior de la cara (AC) y ancho superior de la cara (AC). Los ángulos del triángulo óseo cigomático y el ángulo anterior porion-nasion-epina nasal se midieron desde la vista lateral del cráneo. Si bien no hubo una diferencia significativa entre la medición derecha e izquierda, a excepción AP (p = 0,03), la distancia de FIP a MI mostró una correlación positiva de alto grado entre los lados derecho e izquierdo, la distancia de FIO a AP fue débil correlacionado solo en el lado derecho.

Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia.

This study describes the encapsulation of the local anaesthetic lidocaine (LDC) in large unilamellar liposomes (LUV) prepared in a scalable procedure, with hydrogenated soybean phosphatidylcholine, cholesterol and mannitol. Structural properties of the liposomes were assessed by dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy. A modified, two-compartment Franz-cell system was used to evaluate the release kinetics of LDC from the liposomes. The in vivo anaesthetic effect of liposomal LDC 2% (LUVLDC) was compared to LDC 2% solution without (LDCPLAIN) or with the vasoconstrictor epinephrine (1:100 000) (LDCVASO), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250 nm and low polydispersity even after LDC incorporation. Zeta potential laid around -30 mV and the number of suspended liposomal particles was in the range of 1012 vesicles/mL. Also the addition of cryoprotectant (mannitol) did not provoke structural changes in liposomes properties. In vitro release profile of LDC from LUV fits well with a biexponential model, in which the LDC encapsulated (EE% = 24%) was responsible for an increase of 67% in the release time in relation to LDCPLAIN (p < 0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (∼70 min), in comparison with LDCPLAIN (45 min), but less than LDCVASO (130 min). In this context, this study showed that the liposomal formulations prepared by scalable procedure were suitable to promote longer and safer buccal anaesthesia, avoiding side effects of the use of vasoconstrictors.

Eficacia de la técnica infraorbitaria en incisivos y premolares maxilares usando lidocaína al 2% con epinefrina 1:80,000 / Anesthetic efficacy of the infraorbital nerve block in maxillary incisors and premolars using 2% lidocaine with epinephrine 1:80,000

Objetivos: Los autores condujeron un ensayo clínico no controlado para determinar la efectividad de la técnica infraorbitaria, para proporcionar anestesia pulpar profunda en incisivos y premolares maxilares. Material y métodos: Diecinueve adultos voluntarios recibieron 1.8 mililitros de lidocaína al 2% con epinefrina 1:80,000 con una técnica infraorbitaria intraoral. Los investigadores usaron un electric pulp tester (vitalómetro) para medir la anestesia pulpar en incisivos y premolares maxilares. Los participantes informaron sobre anestesia en tejidos blandos, y molestias durante la inyección además de que valoraron el tiempo de inicio de la anestesia y la duración de la misma. Los autores analizaron los datos usando el programa estadístico STATA 9®. Resultados: La mayoría de los sujetos tenía 21 años (30%), el sexo más común fue el sexo femenino (n = 12-60%). Los autores evaluaron con escala visual análoga (VAS), la percepción del dolor al momento de aplicar la anestesia, encontrando que el 57.9% de los pacientes (n = 11) lo catalogaron como moderado (escala de 3-6). Al evaluar el éxito anestésico, observaron un mayor número de episodios en el canino y el primer premolar (57.9%, n = 9 - IC 95%), Los autores observaron un importante número de fallas en la anestesia pulpar de incisivos centrales y laterales (100-84.2%, respectivamente). El inicio de la anestesia fue a los 12-19 minutos, siendo el canino el de mayor número de reportes con un 47.4%. La incidencia de sensación subjetiva de anestesia de los tejidos blandos en piel de párpado, ala de la nariz y piel de labio superior fue del 100%, los autores observaron que el 100% de los sujetos la calificaron como desagradable (VAS). Conclusiones: La técnica infraorbitaria produce anestesia exitosa en sólo el 57.9% de los caninos y primeros premolares maxilares; es ineficaz para anestesiar incisivos centrales y laterales, luego de ser evaluada con un riguroso test de vitalometría, se produce anestesia de tejidos blandos que es catalogada como incomoda. Los autores consideran que la utilidad de la técnica infraorbitaria en odontología es cuestionable y se deben considerar otras técnicas para los incisivos y premolares maxilares.

Objectives: The authors conducted a clinical-trial, uncontrolled study to determine infraorbital nerve block effectiveness. Material and methods: Nineteen adult volunteers received 1.8 mL of lidocaine 2% with epinephrine 1:80,000 with an intraoral, infraorbital nerve block. Researchers used an electric pulp tester to measure pulp anesthesia in maxillary incisors and premolars. Participants reported soft tissue anesthesia and discomfort during the injection procedure; anesthesia onset time and its duration were also assessed and analyzed. Authors analyzed data using STATA statistical program 9®. Results: Most of the subjects in our trial were 21 years old (30%); the number of female participants (n = 12 - 60%) was greater than that of male participants. Authors evaluated pain perception when injecting anesthesia with a visual analogue scale (VAS), finding that 57.9% of patients (n = 11) categorized the pain as moderate (in a scale of 3-6). When assessing anesthesia success, it was observed that a greater number of canine teeth and first premolars (57.9%, n = 9 - CI 95%) were anesthetized. The authors also observed a significant greater number of nonresponse (non-anesthetized) cases in central and lateral incisors (100-84.2%, respectively). Anesthesia onset was at 12 to 19 minutes, with canines exhibiting the largest number of anesthetized reports with 47.4%. There was a 100% incidence of subjective feeling of soft tissue anesthesia in lower eyelid skin, skin of the nose and skin of the upper lip. Authors noted that 100% of the subjects rated it as unpleasant (VAS). Conclusions: Infraorbital anesthesia technique achieved successful anesthesia in only 57.9% of upper canines and first premolars; it proved ineffective for anesthetizing central and lateral incisors. This was demonstrated after these teeth were evaluated using rigorous pulp vitality testing. Soft tissue anesthesia occurred and it was classified as uncomfortable. Authors consider that usefulness of infraorbital nerve block technique in dentistry was questionable.

Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects.

[Infraorbital schwannoma. Case report]. / Schwannoma infraorbitario. Informe de un caso.

BACKGROUND: Infraorbital schwannoma is a benign tumor of the peripheral nerve seath composed of Schwann cells. Usually occurs between 20 and 70 years of age, are usually asymptomatic and can cause progressive, painless proptosis during growth. CLINICAL CASE: A 32-year-old male admitted to ophthalmologic hospital with a painless, slowly progressive mass above the left lacrimal sac. At the ophthalmologic examination the tumor had a rubbery consistency and was firmly attached to the surrounding structures. The transillumination was negative. The B mode ultrasound disclosed a phakic eye as well as an infraorbital well-circumscribed homogeneous mass with a largest diameter of 19.7 mm, without involvement of the lacrimal pathway. The A mode ultrasound showed medium-high reflectivity with small internal vascularity. The computed tomography showed a homogeneous wellcircumscribed solid mass anterior and inferior to the left globe without bony erosion. Through subdermic incision the mass was excised. The histopathological diagnosis was "Infraorbital schwannoma". CONCLUSIONS: The schwannoma is a rare benign tumor in the orbit, few cases have been reported. The definitive diagnosis is made by histopathologic findings as the presence of a true capsule, hyper-and hypocellular areas, thickening and hyalinization of the vessel walls. When these findings are not be confused with benign fusocellular tumors. We report a new case of infraorbital schwannoma and compared it with those cases previously reported.

Antecedentes: el schwannoma infraorbitario es un tumor benigno de la vaina nerviosa periférica compuesto por células de Schwann. Suele aparecer entre los 20 y 70 años de edad, asintomático y producir proptosis progresiva e indolora durante su crecimiento. Caso clínico: paciente masculino de 32 años de edad que ingresó al hospital debido a un tumor no doloroso de crecimiento lentamente progresivo sobre el saco lagrimal izquierdo. A la exploración oftalmológica el tumor era de consistencia ahulada y estaba firmemente adherido a las estructuras vecinas. La transiluminación resultó negativa. El ultrasonido modo B mostró un ojo fáquico y un tumor infraorbitario homogéneo, bien circunstrito, con diámetro mayor de 19.7 mm, sin afectación de la vía lagrimal. El ultrasonido modo A mostró una reflectividad media-alta, con escasa vascularidad interna. La tomografía computada mostró un tumor de densidad homogénea, bien circunscrito a la región anterior y por debajo del globo ocular, sin erosión ósea. El tumor se extirpó mediante una incisión subdérmica. El diagnóstico histopatológico fue: schwannoma infraorbitario. Conclusiones: el schwannoma es un tumor benigno, poco frecuente en la órbita. Su diagnóstico definitivo se establece con base en los hallazgos histopatológicos, como: cápsula verdadera, áreas hiper e hipocelulares, engrosamiento y hialinización de las paredes vasculares. Sin esos hallazgos puede confundirse con tumores fusocelulares benignos. Se informa un nuevo caso de schwannoma infraorbitario y se compara con los casos previamente reportados.