Infraorbital Nerve Research Articles

Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.

Reconstruction of the Infraorbital Nerve Using Bilayered Artificial Nerve Conduits after Partial Maxillectomy.

Facial sensory nerves play vital roles in daily functions like self-protection, facial expressions, speaking, and eating. Severing the infraorbital nerve (ION) during partial maxillectomy via the Weber-Ferguson incision can lead to sensory disturbances. This study presents immediate ION reconstruction using artificial nerve conduits and its short-term outcomes. This retrospective study included three patients (mean age: 67.0 years) undergoing immediate ION reconstruction after partial maxillectomy via the Weber-Ferguson incision. Sensory recovery was evaluated using the Semmes-Weinstein and two-point discrimination (2PD) tests. A reference group of five patients who underwent total maxillectomy without ION reconstruction was also assessed. No postoperative complications were observed during the 15.3-month follow-up. Sensory recovery varied among patients, with one achieving normal perception at 24 months, another showing diminished light touch at 13 months, and the third experiencing diminished protective sensation at 7 months postoperatively. In comparison, the reference group showed lower sensory recovery. Two patients showed improvements in 2PD test results at 24 and 13 months, whereas one showed no recovery at 7 months. No patients in the reference group showed improvement. Immediate ION reconstruction using artificial nerve conduits after partial maxillectomy appears feasible, as evidenced by acceptable sensory recovery in the short term.

Assessing the Adequacy of Orbital Reconstruction With Titanium Mesh Using Clinical and Radiological Measures.

Background Orbital reconstruction aims to restore the original orbit volume and correct diplopia, enophthalmos, and ocular motility of the fractured orbit. This study aimed to assess the adequacy of orbital reconstruction using radiological and clinical factors. Methods In this retrospective study, patients with orbital blowout fractures meeting clinical or radiographic criteria underwent orbital reconstruction with titanium mesh. The orbital volume and anteroposterior displacement were calculated pre- and post-operatively using computed tomography. Diplopia, inferior orbital nerve examination, and ocular movement were also evaluated. Pre- and post-operative orbital volumes of the fractured and contralateral unfractured orbits were compared. Statistical analysis was performed using MS Excel (Redmond, USA) and STATA BE (Texas, US). Results There was a significant reduction in the difference in volumes between fractured and normal orbits postoperatively (p-value <0.001). The mean difference between the reconstructed orbital floor fracture and the contralateral normal orbit was 0.55 cm3, which is within the normal anatomic variation. Enophthalmos was corrected postoperatively in our patients per radiological parameters as a result of a reduction in the mean posterior displacement. Infraorbital nerve hypoesthesia was not resolved postoperatively. Conclusion Our study highlights the restoration of the normal anatomical variation in volume differences between the fractured and contralateral orbits post-surgery using CT-guided analysis, thereby improving clinical outcomes.

Structural reorganization of medullary dorsal horn astrocytes in a rat model of neuropathic pain.

Multiple studies have shown that astrocytes in the medullary dorsal horn (MDH) play an important role in the development of pathologic pain. However, little is known about the structural reorganization of the peripheral astrocytic processes (PAP), the main functional part of the astrocyte, in MDH in neuropathic state. For this, we investigated the structural relationship between PAP and their adjacent presynaptic axon terminals and postsynaptic dendrites in the superficial laminae of the MDH using electron microscopical immunohistochemistry for ezrin, a marker for PAP, and quantitative analysis in a rat model of neuropathic pain following chronic constriction injury of the infraorbital nerve (CCI-ION). We found that, compared to controls, in rats with CCI-ION, (1) the number, % area, surface density, and volume fraction of ezrin-positive (+) PAP, as well as the fraction of synaptic edge apposed by ezrin + PAP and the degree of its coverage of presynaptic axon terminals and postsynaptic dendrites increased significantly, (2) these effects were abolished by administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP). These findings indicate that PAP undergoes structural reorganization around the central synapses of sensory afferents following nerve injury, suggest that it may be mediated by mGluR5, and may represent the structural basis for enhancing astrocyte-neuron interaction in neuropathic pain.

The Role of Astrocyte-Neuron Lactate Shuttle in Neuropathic Orofacial Pain.

Inhibition of astrocytic energy metabolism alleviates neuropathic pain. To explore whether astrocyte-neuron lactate shuttle (ANLS) played any role in neuropathic orofacial pain. Rats with partial transection of the right infraorbital nerve (p-IONX) or sham operation were intrathecally injected with acetazolamide (a carbonic anhydrase inhibitor), bithionol (a soluble adenylyl cyclase inhibitor), α-cyano-4-hydroxycinnamic acid [α-CHCA, a monocarboxylate transporter (MCT) inhibitor] or vehicle once a day from postoperative day 1-14. The facial mechanical thresholds were tested on preoperative day 1 and 2 and postoperative days 1, 3, 5, 7, 10 and 14, expression of glucose transporters (GLUTs) and MCTs in the trigeminal subnucleus caudalis (Vc) were examined on the postoperative day 3 and neuronal activities in the Vc were examined in the p-IONX rats on postoperative days 3-5. Compared with the sham group, the mechanical thresholds in the p-IONX group were significantly reduced at postoperative days 1-7, and the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 was significantly increased on postoperative day 3. In the p-IONX groups, neurons in the Vc were sensitised, and acetazolamide, bithionol and α-CHCA reversed the central sensitisation, significantly increased the mechanical thresholds at postoperative days 1-7 and decreased the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 at postoperative day 3 compared with those in the vehicle-treated rats. Inhibition of ANLS alleviates p-IONX-related neuronal, behavioural and immunohistochemical changes, which suggests that ANLS plays an important role in trigeminal neuropathic pain.

Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain

BackgroundWidespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking.MethodsWidespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain.ResultsWe found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain.ConclusionThese results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Contrast-free visualization of distal trigeminal nerve segments using MR neurography.

The 3-dimensional cranial nerve imaging (CRANI) sequence may assist visualization of anatomical details of extraforaminal cranial nerves and aid in clinical diagnosis and preoperative planning. In this study, we investigated the feasibility of using a combined CRANI and magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) imaging protocol to comprehensively identify trigeminal nerve projections. We evaluated the detection of distal regions of three branches of the ophthalmic nerve (V1), three branches of the maxillary nerve (V2), and five branches of the mandibular nerve (V3) in seven healthy adult subjects, with and without contrast injection. Nerve branches were rated on a 5-point scale by three observers. Interobserver reliability was studied using weighted kappa statistics and percentage agreement. Among V1 and V2 branches, the frontal nerve and infraorbital nerve were most successfully identified (average rating of 3.9, agreement >80%) in precontrast MPRAGE images. In V3 branches, lingual and inferior alveolar nerves were most successfully identified (average rating of 3.9, agreement >80%) in precontrast CRANI images, with an excellent average rating. In all cases except one, interobserver reliability was rated good to excellent. The buccal nerve was the only branch with a low average interobserver rating. Gadolinium contrast did not improve nerve segment visualization in our study. This may relate to the specific anatomic regions assessed, gadolinium dose, postcontrast image timing, and lack of pathology. A combined CRANI and MPRAGE protocol can be combined to visualize distal branches of V1, V2, and V3 and has potential for clinical use.

Normative Measurements of the Infraorbital Nerve by Magnetic Resonance Imaging in an Australia Cohort.

To report the normative dimensions of the infraorbital nerve on fat-suppressed gadolinium-enhanced MRI and correlate with patient demographics in an Australian cohort. A retrospective review of patients who underwent coronal fat-suppressed gadolinium T1-weighted MRI from September 2021 to December 2023. One hundred sixty-eight orbits were included. The maximum diameter of the infraorbital nerve and the optic nerve sheath was measured. Orbits were excluded if there was unilateral or bilateral pathology of the infraorbital nerve or optic nerve sheath, incomplete MRI sequences, poor image quality, or indiscernible infraorbital nerve on radiological examination. The mean age of participants was 58 ± 16 years, and 50% were females (n = 42). The mean normative measurements (mean ± standard deviation) on coronal T1-weighted imaging: optic nerve sheath, 5.08 ± 0.67 mm. On coronal fat-suppressed gadolinium T1-weighted imaging: infraorbital nerve, 0.89 ± 0.22mm. No significant differences were found between male or female participants in both the infraorbital nerve (p = 0.757) or optic nerve sheath (p = 0.646). There was no significant correlation between age and mean diameter of the infraorbital nerve (r = 0.077, p = 0.320) or optic nerve sheath (r = 0.075, p = 0.336). Additionally, no significant difference was identified between the mean diameter of the infraorbital nerve (p = 0.079) and optic nerve sheath (p = 0.120) across age groups. The mean infraorbital nerve to optic nerve sheath ratio was 0.18 ± 0.00. Normative dimensions of the infraorbital nerve may be used to identify enlargement in conditions such as IgG4-related ophthalmic disease and reactive lymphoid hyperplasia.

Three-dimensional computer navigation in the reconstruction of complex unilateral orbital fractures: evaluation and review of applications.

The eyes are the central aesthetic unit of the face. Maxillofacial trauma can alter facial proportions and affect visual function with varying degrees of severity. Conventional approaches to reconstruction have numerous limitations, making the process challenging. The primary objective of this study was to evaluate the application of three-dimensional (3D) navigation in complex unilateral orbital reconstruction. A prospective cohort study was conducted over 19 months (January 2020 to July 2021), with consecutive enrollment of 12 patients who met the inclusion criteria. Each patient was followed for a minimum period of 6 months. The principal investigator carried out a comparative analysis of several factors, including fracture morphology, orbital volume, globe projection, diplopia, facial morphic changes, lid retraction, and infraorbital nerve hypoesthesia. Nine patients had impure orbital fractures, while the remainder had pure fractures. The median orbital volume on the normal side (30.12 cm3; interquartile range [IQR], 28.45-30.64) was comparable to that of the reconstructed orbit (29.67 cm3; IQR, 27.92-31.52). Diplopia improved significantly (T(10) = 2.667, p = 0.02), although there was no statistically significant improvement in globe projection. Gross symmetry of facial landmarks was achieved, with comparable facial width-to-height ratio and palpebral fissure lengths. Two patients reported infraorbital hypoesthesia at presentation, which persisted at the 6-month follow-up. Additionally, five patients developed lower lid retraction (1-2 mm), and one experienced implant impingement at the infraorbital border. Our study provides level II evidence supporting the use of 3D navigation to improve surgical outcomes in complex orbital reconstruction.

Recovery of the Infraorbital Nerve Following Open Reduction and Fixation Surgery of Zygomaticomaxillary Complex Fractures-A Prospective Cohort Study Based on Quantitative Sensory Testing.

This study aimed to assess the sensory function of the infraorbital nerve in patients with fractures of the zygomatic complex who underwent open reduction and internal fixation at different time points using quantitative sensory testing, which was established by the German Neuropathic Pain Research Network, comprising a 7-item mechanical and thermal sensory test. A total of 21 patients (age range 17-46y, 14 males) with unilateral zygomatic complex fractures were included. Quantitative sensory testing was conducted before the operation and at 1 week, 3 months, and 6 months operatively, with cold detection threshold, warmth detection threshold, cold pain threshold, heat pain threshold, mechanical detection threshold, mechanical pain threshold, pressure pain threshold, and vibration detection threshold being measured in bilateral infraorbital regions. Notable changes in sensitivity were observed in all values except for the mechanical pain threshold. In the majority of patients with zygomaticomaxillary complex fractures, infraorbital hypoesthesia was significantly improved within 3 months postoperatively, and almost complete recovery could be achieved by 6 months postoperatively.

Different mechanisms guide the antinociceptive effect of bone marrow-mononuclear cells and bone marrow-mesenchymal stem/stromal cells in trigeminal neuralgia

AimsTrigeminal neuralgia (TN) is a type of chronic orofacial pain evoked by trivial stimuli that manifests as episodes of excruciating and sudden, recurrent paroxysmal pain. Most patients are refractory to pharmacological therapy used for the treatment of TN. Mononuclear cells (MNC) and mesenchymal stem/stromal cells (MSC) have shown therapeutic potential in painful neuropathies, but their mechanism of action is not fully understood. The present work aimed to investigate the antinociceptive effect and mechanism of action of MNC and MSC in experimental TN. Materials and methodsMice submitted to the chronic constriction injury of the infraorbital nerve (CCI-ION) mouse model of TN received a single intravenous injection of saline, MNC, or MSC (1 × 106 cells/mouse). The effect of the treatments on the behavioral signs of painful neuropathy, morphological aspects of the infraorbital nerve, and inflammatory and oxidative stress markers in the infraorbital nerve were assessed. Key findingsMNC and MSC improved behavioral painful neuropathy, activated key cell signaling antioxidant pathways by increasing Nrf2 expression, and reduced the proinflammatory cytokines IL-1β and TNF-α. However, treatment with MSC, but not MNC, was associated with a sustained increase of IL-10 and with the re-establishment of the morphometric pattern of the infraorbital nerve, indicating a difference in the mechanism of action between MNC and MSC. In line with this result, in IL-10 knockout mice, MSC transplantation did not induce an antinociceptive effect. SignificanceImportantly, these data suggest an IL-10-induced disease-modifying profile related to MSC treatment and reinforce cell therapy's potential in treating trigeminal neuralgia.

OTULIN's influence on neuroinflammation and pain modulation in trigeminal neuralgia.

Trigeminal neuralgia (TN), marked by chronic pain from neural damage, is closely associated with inflammation. The role of OTULIN, a key regulator in inflammation and autophagy, is not fully understood in TN. The regulatory mechanism of OTULIN, a key protein involved in modulating inflammatory responses and autophagy processes, remains incompletely elucidated, particularly in the context of TN and neuroinflammation. An infraorbital nerve ligation-induced rat model of TN was used. OTULIN's expression was modulated using adenovirus vectors and short hairpin RNA. The impact on pain and inflammatory responses was assessed via quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and transcriptomic analysis. Enhanced OTULIN expression significantly increased head withdrawal thresholds and reduced pain sensitivity and neuroinflammatory markers in the model. Conversely, silencing OTULIN exacerbated pain and inflammation. Transcriptomic data revealed OTULINs influence on both inflammatory and autophagy pathways, specifically in suppressing NLR family pyrin domain containing 3 (NLRP3) inflammasome and promoting autophagy. Invitro experiments demonstrated OTULIN's inhibition of inflammatory markers in microglia and neurons. OTULIN is crucial in modulating TN, reducing neuropathic pain and neuroinflammation by activating the autophagy pathway and inhibiting the NLRP3 inflammasome.

Anatomical Variations of the Canalis Sinuosus: A CBCT Study

Objective: Canalis sinuosus (CS) is a bony canal separated from the infraorbital nerve containing the anterior superior alveolar vessel-nerve bundle. This study aimed to assess the anatomical variations of the canalis sinuosus from cone-beam computed tomography (CBCT) images. Methods: CBCT images of 568 patients (328 females and 240 males; aged between 18 and 81 years old) were evaluated retrospectively. Axial, sagittal, coronal, and cross-sectional images with 0.5 mm slice thicknesses were used to evaluate the presence of CS and associated accessory canal (AC). Results: Bilateral CS was detected in the entire sample (n=568, 100%). A total of 340 ACs were detected, including at least one AC in 41.9% of the patients. The median value of AC diameter was calculated as 0.89 mm both for females and males. ACs were found in 135 females and in 103 males. One up to five ACs were found per patient. However, the majority of the patients had one AC. ACs were mostly located at tooth region 11 (17.9%) and tooth region 12 (16.4%). Only 59.71% of ACs had a radiographically observed foramen. Conclusion: In conclusion, all patients had CS and ACs were in nearly half of the patients. Knowledge about these structures aid to correct radiographic diagnosis of these canals and minimize the risk of complications during surgical procedures.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Assessment of recovery time for the functional status of infraorbital nerve in open versus closed reduction of zygomatico-maxillary complex fractures: a comparative study

&lt;p&gt;Background and Objective: Zygomatico-maxillary complex (ZMC) fractures and associated infraorbital nerve paresthesia are the most prevalent features of facial trauma associated with road traffic accidents, accidental falls, and violent assaults. The objective of this study was to assess the recovery time of the infraorbital nerve functional status in individuals with paresthesia after open and closed reduction of ZMC fractures.&lt;/p&gt; &lt;p&gt;Method: A comparative cohort study was conducted in the Oral and Maxillofacial Surgery Department of Mayo Hospital in Lahore. The study comprised 100 patients with unilateral isolated en bloc ZMC fractures and post-traumatic paresthesia. Patients were equally divided into two groups: Group A comprised of patients who underwent closed reduction while patients of Group B had open reduction with micro plate osteosynthesis. Demographic information, infraorbital nerve healing, post-op complications, and patients&amp;rsquo; satisfaction were documented. To compare the outcomes of the two groups, statistical analyses were done and p-value &amp;lt;0.05 was taken as statistically significant.&lt;/p&gt; &lt;p&gt;Results: The age distribution revealed a mean age of 37.43 &amp;plusmn; 11.06 years, with 72% of the participants being males. In 63% of patients, there was overall functional nerve recovery. After 6 weeks, 74% of those in Group A (closed reduction) had functional nerve recovery, as compared to 52% of those in Group B (open reduction) (p = 0.023). Age subgroup analysis revealed no significant differences in the recovery rates. When compared to Group-A, patients in Group-B showed faster sensory improvement and better satisfaction levels. Complication rates were equal for both approaches.&lt;/p&gt; &lt;p&gt;Conclusion: In ZMC fractures with paresthesia, both open and closed reduction procedures yielded good results in recovering infraorbital nerve function; however, the open reduction technique demonstrated quicker sensory recovery and more patient satisfaction.&lt;/p&gt;

Treatment Strategy for the Retention Cyst of the Maxillary Sinus

Retention cysts are commonly found in the maxillary sinus and are discovered incidentally on imaging studies. Obstruction of the ducts of the seromucous glands of the paranasal sinus lining is thought to induce the development of retention cysts. Since retention cysts are asymptomatic and tend to degenerate, they do not require definite treatment. However, in clinical practice, surgical treatment is often performed without clear indications. Retention cysts need to be surgically managed when accompanied with relevant clinical symptoms or with obstruction of the natural ostium, or when involving the ostiomeatal complex or the infraorbital nerve. Endoscopic sinus surgery has become the surgical procedure of choice for removing retention cyst. Therefore, it is important for rhinologists to understand the nature and behavior of this pathology so that unnecessary surgical intervention could be avoided.

Anatomical Studies Evaluating Pediatric Regional Anesthesia: A Scoping Review

Background: Pediatric regional anesthesia has been driven by the gradual rise in the adoption of opioid-sparing strategies and the growing concern over the possible adverse effects of general anesthetics on neurodevelopment. Nonetheless, performing regional anesthesia studies in a pediatric population is challenging and accounts for the scarce evidence. This study aimed to review the scientific foundation of studies in cadavers to assess regional anesthesia techniques in children. Methods: We searched the following databases MEDLINE, EMBASE, and Web of Science. We included anatomical cadaver studies assessing peripheral nerve blocks in children. The core data collected from studies were included in tables and comprised block type, block evaluation, results, and conclusion. Results: The search identified 2409 studies, of which, 16 were anatomical studies on the pediatric population. The techniques evaluated were the erector spinae plane block, ilioinguinal/iliohypogastric nerve block, sciatic nerve block, maxillary nerve block, paravertebral block, femoral nerve block, radial nerve block, greater occipital nerve block, infraclavicular brachial plexus block, and infraorbital nerve block. Conclusion: Regional anesthesia techniques are commonly performed in children, but the lack of anatomical studies may result in reservations regarding the dispersion and absorption of local anesthetics. Further anatomical research on pediatric regional anesthesia may guide the practice.

MicroRNA-6954-3p Downregulation Contributes to Orofacial Neuropathic Pain in Mice Via Targeting Voltage-Gated Sodium Channel β2 Subunit Protein

The voltage-gated sodium channel β2 subunit protein (SCN2B) plays a crucial role in neuropathic pain. However, the role and mechanisms of SCN2B in orofacial neuropathic pain are still unclear. This study aimed to investigate the upstream regulatory mechanisms of SCN2B in the trigeminal ganglion (TG) underlying orofacial neuropathic pain. Chronic constriction injury of the infraorbital nerve (CCI-ION) of mice was performed to establish the model of orofacial neuropathic pain. Von Frey filament test was performed to detect the head withdrawal threshold (HWT) of mice. Quantitative reverse transcription-polymerase chain, western blotting (WB), fluorescence in situ hybridization, and immunofluorescence (IF) staining were used to detect the expression and distribution of SCN2B and miR-6954-3p in the TG of mice. A luciferase activity assay was carried out to prove the binding between SCN2B messenger ribonucleic acid (mRNA) and miR-6954-3p. After the CCI-ION surgery, the levels of Scn2b mRNA and protein significantly increased and miR-6954-3p decreased in the TG of mice with decreasing HWT. IF staining revealed that SCN2B was expressed specifically in the TG neurons. Silencing SCN2B in the TG of CCI-ION mice significantly increased the HWT. Importantly, the 3′-untranslated region of Scn2b mRNA was proved to bind with miR-6954-3p. Fluorescence in situ hybridization and IF staining demonstrated that miR-6954-3p was expressed in TG neurons and co-expressed with SCN2B. Furthermore, intraganglionic injection of miR-6954-3p agomir into the TG of CCI-ION mice resulted in the downregulation of SCN2B and increased the HWT. These findings suggest that the downregulation of miR-6954-3p in the TG promotes orofacial neuropathic pain by promoting SCN2B expression following trigeminal nerve injury. PerspectiveThis study points to the important role of SCN2B in orofacial neuropathic pain. Furthermore, miR-6954-3p is proven to regulate the expression of SCN2B by binding to the 3′-untranslated region of Scn2b mRNA. These findings indicate that SCN2B and miR-6954-3p are potential therapeutic targets for the treatment of orofacial neuropathic pain.

Infraorbital nerve block for pain management in pediatric cleft lip surgery in resource-limited areas of Indonesia: A case series

Introduction and importanceCleft lip and palate (CLP) are congenital anomalies of the craniofacial region, commonly found in low- and middle-income countries, including Indonesia. Surgical correction of clefts typically begins at around three months of age to support infant growth. An infraorbital nerve block is an option for regional anesthesia in CLP surgery. This case series aims to determine the effectiveness of infraorbital nerve block in pain management for pediatric CLP surgery. Case presentationThis case series includes five patients who fulfilled the Millard criteria for CLP surgery. All patients received general anesthesia followed by an infraorbital nerve block with 0.2 % ropivacaine in the infraorbital foramen area using the intraoral approach. Data were collected preoperatively, intraoperatively, and postoperatively. DiscussionThe combination of general anesthesia and infraorbital nerve block resulted in stable hemodynamics, low delirium scores, low pain intensity, and adequate oral intake postoperatively. ConclusionInfraorbital nerve block with ropivacaine provides intraoperative hemodynamic stability, decreased delirium, and effective postoperative pain management in pediatric patients undergoing CLP surgery.

Interleukin-22 receptor 1-mediated stimulation of T-type Ca2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

BackgroundInterleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24’s role in peripheral nociception remain unclear.MethodsUsing patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels).ResultsIL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2.ConclusionOur findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.