Food impaction on three-dimensional printed models with periodontal ligament simulation.

OBJECTIVE: This study aims to evaluate food impaction on three-dimensional (3D) printed models with periodontal ligament simulation. MATERIALS AND METHODS: Based on a commercial typodont pair, 3D maxillary and mandibular models were created with no teeth and with tooth sockets that were 1 mm wider than the original ones from 24 to 27 or 34 to 37 for periodontal ligament simulation with vinyl polysiloxane impression material. In total, 35 pairs of 7 combinations, including maxillary/mandibular typodonts in occlusion with maxillary/mandibular 3D models with/without a distal gap of canines on 3D models (tooth 23 or 33) were mounted on hinge articulators and divided into seven groups (n = 5). Each sample experienced the same manual chewing simulation on a customized device. The proximal surfaces were photographed to measure the percentage of food impaction area using ImageJ software. RESULTS: Group with fixed maxillary and mandibular teeth showed more food impaction than other groups with significant differences in the average of maxilla and the average of all proximal areas. CONCLUSION: The flexibility of the periodontal ligament and the degree of freedom of the teeth in their sockets may contribute to the extent of food impaction in proximal spaces.

Coffee-stained tooth enamel color restoration and surface abrasion with whitening and regular toothpaste.

PURPOSE: To evaluate the effectiveness of whitening toothpaste in restoring tooth color after coffee staining and its potential impact on enamel surfaces compared with regular toothpaste. METHODS: Bovine tooth enamel specimens were prepared and stained with coffee solutions before undergoing brushing simulation with different toothpaste slurries (whitening, regular, reference). For precise evaluation, spectrophotometric measurements were taken at intervals to assess color changes using the CIELAB (Commission Internationale de l'Éclairage Lab*) color space. Additionally, profilometric measurements were taken to determine the impact of toothpaste type on the roughness and abraded depth of the enamel surface. To understand the effects of toothpaste and brushing on color change, surface roughness, and abraded depth, while also considering correlations between these factors, the findings were analyzed using mixed-effects models. RESULTS: The whitening toothpaste group demonstrated the highest recovery rate (71%) after 10,000 brushstrokes, followed by the regular toothpaste group (48%) and the reference slurry group (43%). The mixed-effects model analysis revealed that the reference group had a smaller change in lightness (ΔL) than those in the regular toothpaste group. The whitening toothpaste group showed a greater change in lightness on average than those in the regular toothpaste group, with an increase in lightness as the number of brushstrokes increased. According to the roughness and abraded depth data, the whitening toothpaste group was least affected by brushing, while the reference and regular toothpaste groups showed higher levels of roughness and abraded depth at all intervals. CLINICAL SIGNIFICANCE: Gaining a thorough understanding of the effectiveness of whitening toothpaste and its impact on the enamel surface plays a crucial role in refining toothpaste formulations and advancing tooth whitening techniques in dental care.

Examining enamel-surface demineralization upon exposure to acidic solutions and the remineralization potential of milk and artificial saliva.

The enamel surface may undergo demineralization due to exposure to acidic substances and the remineralization of the etched enamel is crucial to regain or maintain integrity. This study aimed to investigate the erosive effect of 10 acidic solutions on tooth enamel and the remineralization capacity of milk and artificial saliva by measuring surface roughness (Ra), enamel depth, and microhardness. A total of 80 bovine incisor enamel specimens were immersed in 10 different acidic solutions, including four different acidic drinks, three different citric acid solutions, and three different citric acid buffer solutions, for 1 h. After demineralization, the specimens were immersed in milk and artificial saliva for 3 h. Surface roughness, enamel abraded depth, and microhardness were measured before demineralization, in-between time intervals and after remineralization. Data were analyzed using Friedman and Kruskal-Wallis tests (p < 0.05). The results indicate a significant difference in surface roughness between the measurements taken at different time intervals, particularly between the baseline and after 1 h demineralization. Also, the specimens immersed in CAB1 exhibited greatest increase in Ra among other acidic solutions (Δ: 0.18 ± 0.07). Moreover, only the microhardness increased after remineralization (p < 0.05). Enamel demineralization using various acidic solutions revealed increased Ra and enamel abraded depth, and decreased microhardness. The use of remineralization agents, milk and artificial saliva, demonstrated an increase in microhardness. This study provides insights into the effects of different acidic solutions and potential remineralization agents on tooth enamel.

Investigating the role of chlorogenic acids and coffee type in coffee-induced teeth discoloration.

OBJECTIVE: Coffee is one of the most popular beverages in the world, with millions of people consuming it every day. The effect of coffee on teeth discoloration has long been a concern for both coffee drinkers and dental professionals. To address this concern, this study aimed to investigate the role of chlorogenic acids (CGAs) and the type of coffee in coffee-induced teeth discoloration. MATERIALS AND METHODS: High-performance liquid chromatography with a photodiode array detector was used to determine the CGA contents of instant coffee produced by five manufacturers (Starbucks, Dunkin' Donuts, Kanu, Ediya, Coffee Bean). A total of 180 bovine tooth specimens were immersed in the coffee samples for varying durations (3, 9, 24, 48, and 72 h), and the discoloration levels were measured using a spectrophotometer. A linear mixed-effects model analysis was used to determine the significance of L*, a*, and b* values in relation to the duration of coffee immersion and coffee type. RESULTS: Both immersion time and coffee type had significant effects on tooth discoloration (p < 0.001), with some types of coffee being more strongly associated with tooth discoloration than others. The amount of CGAs present in coffee was found to be positively correlated with the degree of discoloration (p = 0.030). CONCLUSIONS: Prolonged exposure to coffee can exacerbate teeth staining, and different types of coffee can cause varying degrees of discoloration. Furthermore, coffee with higher levels of CGAs may lead to greater tooth discoloration.

Shear bond strength of orthodontic brackets bonded with primer-incorporated orthodontic adhesives and unpolymerized 3-dimensional printing materials on 3-dimensional-printed crowns.

INTRODUCTION: The use of 3-dimensional (3D) printing techniques in fabricating crowns has increased the demand for bracket bonding onto these surfaces. The objective was to evaluate the shear bond strength (SBS) of orthodontic brackets bonded onto 3D-printed crowns using primer-incorporated orthodontic adhesives and 3D printing materials as orthodontic adhesives. METHODS: A total of 160 crowns were printed with two 3D printing materials, DentaTOOTH (Asiga, Sydney, Australia) (group A) and NextDent C&B Micro Filled Hybrid (3D Systems, Soesterberg, Netherlands) (group N). Each group was randomly divided into 4 adhesive subgroups (n = 20): Transbond XT (for groups A [ATX] and N [NTX]; 3M Unitek, Monrovia, Calif), Ortho Connect (for groups A [AOC] and N [NOC]; GC Corporation., Tokyo, Japan), Orthomite LC (for groups A [AOM] and N [NOM]; Sun Medical, Co Ltd, Moriyama, Shiga, Japan), and unpolymerized liquid state of 3D printing resin (for groups A [AA] and N [NN]). SBS was measured with a universal testing machine at a crosshead speed of 0.5 mm/min. The adhesive remnant index and the mode of failure were analyzed under the microscope. Statistical analysis was performed at a significance level of α = 0.05. RESULTS: When used as adhesives (AA and NN), 3D printing materials showed no statistically significant difference in SBS compared with Transbond XT (ATX and NTX, respectively). In group N, NN showed a significantly higher SBS than primer-incorporated orthodontic adhesives (NOC and NOM; P <0.001). Adhesive failures were only observed in primer-incorporated orthodontic adhesives (AOC, NOC, AOM, and NOM). CONCLUSIONS: Primer-incorporated orthodontic adhesives, as well as unpolymerized 3D printing materials employed as orthodontic adhesives on 3D-printed crowns, exhibited comparable bonding strength to Transbond XT without surface modification. Despite variations in adhesive-related factors, all measurements stayed within clinically acceptable ranges, highlighting the potential of these materials for orthodontic bonding on 3D-printed crowns, simplifying clinical procedures without compromising bond strength.

Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain.

Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC's connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.

Dentin abrasion using whitening toothpaste with various hydrogen peroxide concentrations.

PURPOSE: To compare the amount of abrasion of four whitening toothpastes, two conventional toothpastes, and seven experimental toothpastes with varying concentrations of hydrogen peroxide. METHODS: Bovine dentin specimens were treated with the four whitening toothpastes (containing three different concentrations of hydrogen peroxide: 0.75%, 1.50%, and 2.80%), two conventional toothpastes without hydrogen peroxide, seven experimental toothpastes (concentrations of hydrogen peroxide: 0.75%, 1.50%, 3.0%, 4.50%, 6.0%, 7.50%, and 9.0%), and distilled water. After 10,000 strokes of toothbrushing, the amount of abrasion on the dentin surface was measured with a contactless 3D surface profiler (n= 8). The pH of all solutions, the weight percentages of the particles, and the component of particles in the toothpaste were analyzed. The correlations between the dentin abrasion, pH, and weight percentages of the particles in the toothpastes were investigated. RESULTS: The amount of abrasion of the two conventional toothpastes were 1.1-3.6 times higher than those of the four whitening toothpastes. Likewise, the pH of the conventional toothpaste was higher than those of the other whitening toothpastes. No significant differences were found among the four whitening toothpastes. The four whitening toothpastes consisted of a relatively lower weight percentage of particles compared to the two conventional toothpastes. A strong positive correlation was observed between the dentin abrasion and the weight percentages of the particles (r= 0.913; P< 0.05). Furthermore, no significant differences in the amount of abrasion were observed between the specimens treated with seven experimental toothpastes and those treated with distilled water. CLINICAL SIGNIFICANCE: The whitening toothpastes containing less than 9% hydrogen peroxide did not seem to harm the dentin surface significantly. These findings can serve as a reference for consumers, patients, and dental professionals.

Longterm abrasive and erosive effect of whitening toothpaste on dentin surface.

PURPOSE: To evaluate the amount of dentin loss following immersion in or toothbrushing with whitening toothpaste (WT) containing hydrogen peroxide (HP) and citric acid (CA). Additionally, the amount of dentin loss after brushing with a WT alone or in combination with a conventional toothpaste was assessed, and the effects of HP and CA solutions on the dentin surface were investigated. METHODS: Bovine dentin specimens (n= 350) were randomly assigned to seven solutions of various compositions as toothpaste: The specimens assigned to each solution were then further divided into five treatment groups (n=10 each) : Group A = 1-hour immersion in each solution (ES); Group B = 10,000 brushing in ES; Group C = 1-hour immersion in ES + 10,000 brushing in ES; Group D = 1-hour immersion in ES + 10,000 brushing in reference slurry (RS); Group E = 10,000 brushing in ES + 10,000 brushing in RS. The amount and pattern of dentin loss were determined, and the surfaces were observed using noncontact profilometry. RESULTS: The WT (pH 5.0) caused lower dentin loss than RS after a single brushing cycle; however, the extent of dentin loss after 1 hour of immersion in the WT was significantly greater than that in the RS. Among the specimens treated with WT, a significant difference in dentin loss was observed between Group C and Groups D and E (P< 0.05) but not between Groups D and E. The surfaces exposed to CAS1, CAPB, and WT exhibited U-shaped patterns of dentin loss after brushing or immersion, whereas a wedge-shaped pattern was observed in those that underwent brushing with the RS. CLINICAL SIGNIFICANCE: The effects (dentin abrasion) of a whitening toothpaste containing hydrogen peroxide and citric acid when used in combination with a conventional toothpaste were similar to those seen with the continuous use of a conventional toothpaste alone.

Effects of a commercial whitening toothpaste containing hydrogen peroxide and citric acid on dentin abrasion and erosion.

BACKGROUND: Hydrogen peroxide (HP) and citric acid (CA), key contributors to toothpaste acidity, can lead to dental loss. This study aimed to compare the amount of abrasion or loss of dentin based on pH, buffering, and concentration of HP and CA in commercial and experimental toothpastes after toothbrushing or immersion. METHODS: Bovine dentin specimens were randomly assigned to nine solutions. The prepared solutions included two commercial toothpastes (whitening toothpaste [WT] with HP and CA; conventional toothpaste [CT] without HP and CA), reference slurry (RS), two CA solutions (1.92%, CAS1; 0.001%, CAS2), basic solution (7.16% sodium phosphate dibasic [SPDS]), CA phosphate buffer solution (3.58% SPDS and 0.96% CA [CAPB]), HP solution (4%, HPS), and distilled water (DW). Dentin specimens were performed in two treatments: one with only abrasion (10,000 brushings) and one with only immersion (1 h). After treatments, the amount of dentin loss and surface images were measured and observed using noncontact profilometry. Data were analyzed using an one-way analysis of variance and the Tukey test as a post hoc analysis (p < 0.05). RESULTS: WT with pH 5.0 had lower dentin abrasion than CT and RS after brushing but had higher dentin loss than both after immersion. The dentin surfaces of CAS1, CAPB, and WT were damaged after immersion, whereas HPS, CAS2, CT, SPDS, RS, and DW remained intact after soaking. CAS2 and HPS, which had a pH of 5.0 like WT, did not significantly differ from those of DW after brushing. CONCLUSIONS: WT containing HP and CA did not cause significant dentin abrasion but may cause additional dentin loss even without brushing. After brushing or immersion, the CA concentration may affect the dentin surface more than the HP concentration included in WT. The amount of abrasion or loss of dentin after brushing or soaking can vary based on the composition, concentration, and buffer in the solution, even if the pH of the solution is similar to pH 5.0.

GFAP-NpHR mediated optogenetic inhibition of trigeminal nucleus caudalis attenuates hypersensitive behaviors and thalamic discharge attributed to infraorbital nerve constriction injury.

The significance of hyperactive astrocytes in neuropathic pain is crucial. However, the association between medullary astrocytes and trigeminal neuralgia (TN)-related pain processing is unclear. Here, we examined how optogenetic inhibition of medullary astrocytes in the trigeminal nucleus caudalis (TNC) regulates pain hypersensitivity in an infraorbital nerve (ION) constricted TN model. We used adult Sprague Dawley rats subjected to infraorbital nerve (ION) constriction to mimic TN symptoms, with naive and sham rats serving as controls. For in vivo optogenetic manipulations, rats stereotaxically received AAV8-GFAP-eNpHR3.0-mCherry or AAV8-GFAP-mCherry at the trigeminal nucleus caudalis (TNC). Open field, von Frey, air puff, and acetone tests measured pain behavioral flexibility. In vivo thalamic recordings were obtained simultaneously with optogenetic manipulation in the TNC. Orofacial hyperalgesia and thalamic hyperexcitability were both accompanied by medullary astrocyte hyperactivity, marked by upregulated GFAP. The yellow laser-driven inhibition of TNC astrocytes markedly improved behavioral responses and regulated thalamic neuronal responses. Halorhodopsin-mediated inhibition in medullary astrocytes may modify the nociceptive input transmitted through the trigeminothalamic tract and pain perception. Taken together, these findings imply that this subpopulation in the TNC and its thalamic connections play a significant role in regulating the trigeminal pain circuitry, which might aid in the identification of new therapeutic measures in TN management.

Chrysin Induces Apoptosis via the MAPK Pathway and Regulates ERK/mTOR-Mediated Autophagy in MC-3 Cells.

Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.

Trigeminal ganglion itself can be a viable target to manage trigeminal neuralgia.

Excruciating trigeminal neuralgia (TN) management is very difficult and severely affects the patient's quality of life. Earlier studies have shown that the trigeminal ganglion (TG) comprises several receptors and signal molecules that are involved in the process of peripheral sensitization, which influences the development and persistence of neuropathic pain. Targeting TG can modulate this sensitization pathway and mediate the pain-relieving effect. So far,there are few studies in which modulation approaches to TG itself have been suggested so far. "Trigeminal ganglion modulation" and "trigeminal neuralgia" were used as search phrases in the Scopus Index and PubMed databases to discover articles that were pertinent to the topic. In this review, we address the role of the trigeminal ganglion in TN and underlying molecules and neuropeptides implicated in trigeminal pain pathways in processing pathological orofacial pain. We also reviewed different modulation approaches in TG for TN management. Furthermore, we discuss the prospect of targeting trigeminal ganglion to manage such intractable pain.

Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury.

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model.

BACKGROUND: Preceding studies have reported the association of chronic neuropathic orofacial pain with altered ongoing function in the ventrolateral periaqueductal gray (vlPAG). However, its role in trigeminal neuralgia (TN) lacks attention. We here reported the aspect that vlPAG neurons play in TN nociceptive processing by employing excitatory neuron-specific optogenetic approaches. METHODS: TN was generated via unilateral infraorbital nerve chronic constriction in Sprague Dawley rats which induced mechanical and thermal pain sensitivity in air puff and acetone test, respectively. Channelrhodopsin conjugated virus with CamKIIα promoter was used to specifically activate the excitatory vlPAG neuronal population by optogenetic stimulation and in vivo microdialysis was done to determine its effect on the excitatory-inhibitory balance. In vivo extracellular recordings from ventral posteromedial (VPM) thalamus were assessed in response to vlPAG optogenetic stimulation. Depending on the experimental terms, unpaired student's t test and two-way analysis of variance (ANOVA) were used for statistical analysis. RESULTS: We observed that optogenetic activation of vlPAG subgroup neurons markedly improved pain hypersensitivity in reflexive behavior tests which was also evident on microdialysis analysis with increase glutamate concentration during stimulation period. Decreased mean firing and burst rates were evident in VPM thalamic electrophysiological recordings during the stimulation period. Overall, our results suggest the optogenetic activation of vlPAG excitatory neurons in a TN rat model has pain ameliorating effect. CONCLUSIONS: This article presents the prospect of pain modulation in trigeminal pain pathway via optogenetic activation of vlPAG excitatory neurons in rat model. This outlook could potentially assist vlPAG insight and its optogenetic approach in trigeminal neuropathic pain which aid clinicians endeavoring towards enhanced pain relief therapy in trigeminal neuralgia patients.

Pain modulation effect on motor cortex after optogenetic stimulation in shPKCγ knockdown dorsal root ganglion-compressed Sprague-Dawley rat model.

Neuropathic pain can be generated by chronic compression of dorsal root ganglion (CCD). Stimulation of primary motor cortex can disrupt the nociceptive sensory signal at dorsal root ganglion level and reduce pain behaviors. But the mechanism behind it is still implicit. Protein kinase C gamma is known as an essential enzyme for the development of neuropathic pain, and specific inhibitor of protein kinase C gamma can disrupt the sensory signal and reduce pain behaviors. Optogenetic stimulation has been emerged as a new and promising conducive method for refractory neuropathic pain. The aim of this study was to provide evidence whether optical stimulation of primary motor cortex can modulate chronic neuropathic pain in CCD rat model. Animals were randomly divided into CCD group, sham group, and control group. Dorsal root ganglion-compressed neuropathic pain model was established in animals, and knocking down of protein kinase C gamma was also accomplished. Pain behavioral scores were significantly improved in the short hairpin Protein Kinase C gamma knockdown CCD animals during optic stimulation. Ventral posterolateral thalamic firing inhibition was also observed during light stimulation on motor cortex in CCD animal. We assessed alteration of pain behaviors in pre-light off, stimulation-light on, and post-light off state. In vivo extracellular recording of the ventral posterolateral thalamus, viral expression in the primary motor cortex, and protein kinase C gamma expression in dorsal root ganglion were investigated. So, optical cortico-thalamic inhibition by motor cortex stimulation can improve neuropathic pain behaviors in CCD animal, and knocking down of protein kinase C gamma plays a conducive role in the process. This study provides feasibility for in vivo optogenetic stimulation on primary motor cortex of dorsal root ganglion-initiated neuropathic pain.

Characterization and comparison of genomic profiles between primary cancer cell lines and parent atypical meningioma tumors.

BACKGROUND: Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas. METHODS: We evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor. RESULTS: Our results were consistent with earlier studies that reported mutations in NF2, SMO, and AKT1 genes in atypical meningiomas, and we also observed mutations in MYBL2, a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient. CONCLUSION: Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.

Optical Modulation on the Nucleus Accumbens Core in the Alleviation of Neuropathic Pain in Chronic Dorsal Root Ganglion Compression Rat Model.

OBJECTIVE: The role of the nucleus accumbens (NAc) in chronic neuropathic pain has been suggested, but the role of the NAc in dorsal root ganglion (DRG) neuropathic pain remains unclear. The objective of this study was to determine whether optogenetic stimulation of the NAc influences DRG compression-induced neuropathic pain. MATERIALS AND METHODS: We established sham or DRG lesions in female Sprague-Dawley rats by L4-5 DRG root compression, and the animals received unilateral injections of optogenetic virus in the NAc core. We employed reflexive pain tests to assess the alterations between the groups at the light on/off states. To determine thalamic firing, we performed single-unit in vivo extracellular recording. For statistical analysis, we used one- or two-way repeated-measures analysis of variance. RESULTS: Compared to sham-operated rats, chronic compressed DRG rats showed elevated behavioral sensitivity and sustained neuronal hyperexcitability in the thalamus. NAc optic stimulation improved pain behaviors and lowered thalamic discharge from ventral posterolateral thalamic nuclei. CONCLUSIONS: The NAc core impacts the reward and motivational aspects of chronic neuropathic pain influenced by limbic behaviors to thalamic discharge. Increased thalamic firing activity may result in chronic compressed DRG-induced neuropathic pain, and optogenetic neuromodulation of the NAc can ease chronic pain and thalamic discharge.

Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms.

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke. Recent studies have suggested that variants of RNF213, a susceptibility gene for moyamoya disease (MMD), are also related to non-MMD ICASO. Regarding the predominant involvement of steno-occlusion on anterior circulation in MMD, we hypothesized that the ICASO distribution pattern (anterior/posterior) in non-MMD may differ according to RNF213 variants. This study analyzed 1024 consecutive Korean subjects without MMD who underwent computed tomography angiography (CTA) or magnetic resonance angiography (MRA). We evaluated four single nucleotide polymorphisms (SNPs) in the exon region of RNF213: 4448G > A (rs148731719), 4810G > A (rs112735431), 4863G > A (rs760732823), and 4950G > A (rs371441113). Associations between RNF213 variants and anterior/posterior ICASO were examined using multivariate logistic regression analysis. Anterior ICASO was present in 23.0% of study subjects, and posterior ICASO was present in 8.2%. The GA genotype of RNF213 4810G > A (adjusted odds ratio (AOR) [95% confidence interval (CI)], 2.39 [1.14-4.87] compared to GG; p = 0.018) and GA genotype of RNF213 4950G > A (AOR [95% CI], 1.71 [1.11-2.63] compared to GG; p = 0.015) were more frequent in subjects with anterior ICASO. The genotype frequency of RNF213 4863G > A differed significantly according to the presence of posterior ICASO. Further investigations of the functional and biological roles of RNF213 will improve our understanding of the pathomechanisms of ICASO and cerebrovascular disease.

Optogenetic stimulation of the motor cortex alleviates neuropathic pain in rats of infraorbital nerve injury with/without CGRP knock-down.

BACKGROUND: Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. OBJECTIVE: The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury. METHODS: Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively. RESULTS: We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition. CONCLUSION: Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.

Percutaneously Inserted Unilateral Lead Migration Salvaged with a Paddle Electrode.

INTRODUCTION: Lead migration has been regarded as a frequent complication after percutaneous spinal cord stimulation (SCS). Thus far, repeated reinsertion of leads or replacement of paddle electrodes after removing percutaneous leads has been performed, but a salvage surgical technique using the remaining electrode has not been reported. Here, we describe a case in which unilateral lead migration was successfully treated with the insertion of a paddle electrode. CASE SUMMARY: A 44-year-old male paraplegic patient with chronic neuropathic pain in the right leg and low back for 7 years underwent a percutaneous spinal cord stimulation procedure 5 times over 2 years because of repeated unilateral lead migration. The left lead underwent repeated migration and was difficult to reinsert due to epidural adhesion. After confirming the position and stimulation area of the remaining lead, we decided to insert another paddle electrode beside the remaining lead. We performed a T10 laminotomy and inserted a paddle electrode on the right side, using it in combination with the previous left lead. After surgery, the patient was satisfied with a wide coverage area. DISCUSSION: We recommend salvage additional paddle electrode insertion rather than removing both leads during revision SCS. This surgical method increases the possibility of covering the dorsal column (DC) of the spinal cord, is cost effective, and decreases the possibility of failing to cover dorsal column using the paddle electrode during open surgery because the remaining lead's position and stimulation area guide the insertion of the additional paddle lead.