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Background: Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively., Methods: A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis., Results: SFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1)., Conclusions: In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine., (© 2024. The Author(s).)

Background: Disorders of the trigeminal nerve, a sensory nerve of the orofacial region, often lead to complications in dental practice, including neuropathic pain, allodynia, and ectopic pain. Management of these complications requires an understanding of the cytoarchitecture of the trigeminal ganglion, where the cell bodies of the trigeminal nerve are located, and the mechanisms of cell-cell interactions., Highlights: In the trigeminal ganglion, ganglion, satellite, Schwann, and immune cells coexist and interact. Cell-cell interactions are complex and occur through direct contact via gap junctions or through mediators such as adenosine triphosphate, nitric oxide, peptides, and cytokines. Interactions between the nervous and immune systems within the trigeminal ganglion may have neuroprotective effects during nerve injury or may exacerbate inflammation and produce chronic pain. Under pathological conditions of the trigeminal nerve, cell-cell interactions can cause allodynia and ectopic pain. Although cell-cell interactions that occur via mediators can act at some distance, they are more effective when the cells are close together. Therefore, information on the three-dimensional topography of trigeminal ganglion cells is essential for understanding the pathophysiology of ectopic pain., Conclusions: A three-dimensional map of the somatotopic localization of trigeminal ganglion neurons revealed that ganglion cells innervating distant orofacial regions are often apposed to each other, interacting with and potentially contributing to ectopic pain. Elucidation of the complex network of mediators and their receptors responsible for intercellular communication within the trigeminal ganglion is essential for understanding ectopic pain., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate cellular changes in protein expression in the trigeminal ganglion in an established preclinical chronic model of temporomandibular joint disorder (TMD) in response to grape seed extract (GSE) supplementation based on its beneficial use in preclinical chronic orofacial pain models., Design: Three experimental conditions included female Sprague-Dawley rats as naïve controls, and animals subjected to neck muscle inflammation and prolonged jaw opening with and without daily supplementation of GSE in the drinking water prior to inflammation. Changes were evaluated in mechanical sensitivity to von Frey filaments and protein expression in the trigeminal ganglion of animals 14 days post jaw opening., Results: Calcitonin-gene related peptide and protein kinase A, proteins positively associated with peripheral sensitization and enhanced nociception, did not show elevated expression at day 14 in the model compared to naïve or GSE supplemented animals. However, neuronal levels of glutamate decarboxylase (GAD) 65/67, which are enzymes responsible for the synthesis of the inhibitory neurotransmitter GABA that functions to suppress neuronal excitability, were significantly decreased on day 14 post jaw opening. Similarly, a significant decrease in neuronal expression of the GABA receptor subunits GABAB1 and GABAB2, but not GABAA, was observed in the TMD model. Importantly, GSE prevented suppression of GAD 65/67 and GABAB subunits, maintaining levels similar to naïve animals., Conclusion: Results from our study provide evidence of the downregulation of inhibitory GABAergic proteins in trigeminal ganglion neurons in a preclinical chronic TMD model and the benefits of GSE supplementation in preventing their suppression and maintaining normal levels., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The trigeminal ganglion, the largest of the vertebrate cranial ganglia, is comprised of sensory neurons that relay sensations of pain, touch, and temperature to the brain. These neurons are derived from two embryonic cell types, the neural crest and ectodermal placodes, whose interactions are critical for proper ganglion formation. While the T-cell leukemia homeobox 3 (Tlx3) gene is known to be expressed in placodally-derived sensory neurons and necessary for their differentiation, little was known about Tlx3 expression and/or function in the neural crest-derived component of the developing trigeminal ganglion. By combining lineage labeling with in situ hybridization in the chick embryo, we show that neural crest-derived cells that contribute to the cranial trigeminal ganglion express Tlx3 at a time point that coincides with the onset of ganglion condensation. Importantly, loss of Tlx3 function in vivo diminishes the overall size and abundance of neurons within the trigeminal ganglion. Conversely, ectopic expression of Tlx3 in migrating cranial neural crest results in their premature neuronal differentiation. Taken together, our results demonstrate a critical role for Tlx3 in neural crest-derived cells during chick trigeminal gangliogenesis., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Trigeminal herpetic neuralgia (THN) presents with severe pain hyperalgesia and is a high-risk factor for postherpetic neuralgia (PHN). The current clinical treatments for THN are unsatisfactory, and new treatments are desperately required., Objectives: This pilot study aimed to evaluate the efficacy of short-term trigeminal ganglion stimulation in treating patients with multi-branch THN., Study Design: A prospective pilot study., Setting: Multi-center study in 3 academic hospitals., Methods: From July 2021 to October 2022, we enrolled 20 patients with multi-branch THN who received short-term trigeminal ganglion stimulation under general anesthesia from 3 hospitals. All patients completed a 12-month follow-up. The visual analog scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess patients' pain and quality of sleep. The Barrow Neurological Institute (BNI) score was used to determine the global outcome of pain relief, and complications were recorded., Results: Significant and sustained pain relief and sleep improvement were achieved by all the patients who underwent trigeminal ganglion electrode stimulation in the present study. Respective BNI scores of 80% and 85% at 3 and 12 months after surgery were considered good. There were no other serious complications except for 2 patients' experiences of transient trigeminal cardiac reflex during the surgery and transient numbness deterioration in one patient's V3 sensory area., Limitations: The present study is a pilot study. We expect prospective multi-center, large-sample studies in the future., Conclusion: Short-term trigeminal ganglion stimulation can be used safely and effectively to treat patients with multi-branch THN and significantly reduce the occurrence of PHN.

Orofacial neuropathic pain is a common symptom induced by orofacial nerve injury caused by a range of trauma or dental and maxillofacial procedures but lacks effective treatment. Circular RNAs (circRNAs) participate in the regulatory processes of neuropathic pain. Nevertheless, the biological roles of circRNAs in orofacial neuropathic pain remain unexplored. In this study, circRNA sequencing and Real-time quantitative polymerase chain reaction (RT-qPCR) were carried out. Notably, a novel circRNA named circ_lrrc49 was identified to be downregulated following chronic constriction injury of the infraorbital nerve (CCI-ION) in mice on day 14. Subsequent RNA Antisense Purification (RAP)-mass spectrometry and RNA immunoprecipitation found a direct interaction between circ_lrrc49 and increased sodium tolerance 1 homolog (Ist1). Western blot (WB) identified decreased expression of Ist1 on day 14 post-CCI-ION. Considering the known relationship between Ist1 and autophagy, LC3-II and p62 were detected to be upregulated, and an accumulation of autophagosomes were observed at the same time point. Besides, the knockdown of circ_lrrc49 by small interfering RNA (siRNA) reduced Ist1 expression, increased LC3-II, p62 levels and autophagosomes amount, and evoked orofacial mechanical hypersensitivity, which could be counteracted by the Ist1 overexpression. Similarly, the knockdown of Ist1 by siRNA also increased LC3-II and p62 levels and evoked orofacial mechanical hypersensitivity without influence on circ_lrrc49. Moreover, autophagy activation by rapamycin alleviated orofacial mechanical hypersensitivity evoked by CCI-ION or circ_lrrc49 knockdown. In conclusion, our data revealed the existence of a circ_lrrc49/Ist1/autophagy signaling axis contributing to the progression of orofacial neuropathic pain. These discoveries reveal the intricate molecular processes that drive orofacial neuropathic pain and identify circ_lrrc49 as a promising target for potential therapeutic interventions., (© 2024 International Society for Neurochemistry.)

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1β, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1β, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1β involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, ~11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naïve mice in part by CSF-borne calcitonin gene-related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache.

Objective: Tumors may be responsible for up to 5% of trigeminal neuralgia cases. Predictors of long-term pain relief after surgical resection of various cerebellopontine angle tumor types are not well understood. Previous studies found that size and extent of resection predict long-term pain status, although resection of tumor involving the trigeminal ganglion may be associated with high morbidity. This study evaluated predictors of TN pain freedom after resection of a nonacoustic CPA tumor, with avoidance of any portion involving the TG., Methods: In a retrospective cohort study, we evaluated clinical outcomes and complications after surgical resection of nonacoustic CPA tumors with purposeful avoidance of the TG causing trigeminal neuralgia. The primary outcome was pain-freedom. We performed logistic regression analyses to examine the relationship between pain-freedom at last follow-up and age, side of symptoms, preoperative symptom duration, tumor diameter, tumor type, and concurrent neurovascular compression (NVC)., Results: Of 18 patients with nonacoustic CPA tumors causing TN treated with surgical resection, 83.3% were pain-free at last follow-up (mean 44.6 months). Age (P = 0.12), side (P = 0.41), preoperative symptom duration (P = 0.85), tumor diameter (P = 0.29), tumor type (P = 0.37), and NVC presence (P = 0.075) were not associated with long-term pain freedom., Conclusions: This study provides additional evidence that various tumor types causing TN may safely undergo surgical resection and decompression of the trigeminal nerve to treat TN. This study presents a cohort of patients that underwent resection of a nonacoustic CPA tumor, with purposeful avoidance of the TG to minimize complications, demonstrating high rates of long-term pain freedom., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively. Methods A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis. Results SFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1). Conclusions In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine.

Background. Diseases of the peripheral nervous system account for more than 50 % of all outpatient neurological pathology, and since inflammatory diseases are one of the main problems of medicine, it is important now to develop new methods of anti-inflammatory therapy based on the action of biologically active substances contained in natural products, as well as in many mammalian tissues, particularly in the placental tissue, which is an endocrine gland during pregnancy. Therefore, the issue of using cryopreserved placenta preparations is of great practical importance in the treatment of inflammatory processes and requires further research. The purpose of the work was to investigate the morphometric and morphological features of the trigeminal ganglion of rats in the experimental model of aseptic inflammation and the introduction of cryopreserved placenta. Materials and methods. The work was carried out on 50 sexually mature male rats. The control group consisted of 5 animals who received a single injection of physiological saline solution. Using standard research methods, paraffin blocks were made from which a series of semi-thin sections were cut and stained with hematoxylin and eosin. Histological sections were studied in a light Biorex 3 microscope with a digi­tal camera using software adapted for research. Statistical data processing was performed using Microsoft Office Excel. Results. The morphometric study of rats from the control group revealed that the cytoplasm volume of the bodies of the trigeminal ganglion neurons was 3489.89 ± 37.59 μm3, the volume of the nucleus was 247.68 ± 4.30 μm3. In the experimental model of inflammation and introduction of cryopreserved placenta, destructive phenomena are observed until the seventh day, with marked swelling of the stroma, disruption in the structure of neurons with signs of cytoplasmic swelling, which is confirmed by the data of a morphometric study, namely a reliable increase in the cytoplasm volume by 30.78 % compared to the control group of animals (p

The trigeminal nerve is the sensory afferent of the orofacial regions and divided into three major branches. Cell bodies of the trigeminal nerve lie in the trigeminal ganglion and are surrounded by satellite cells. There is a close interaction between ganglion cells via satellite cells, but the function is not fully understood. In the present study, we clarified the ganglion cells' three-dimensional (3D) localization, which is essential to understand the functions of cell-cell interactions in the trigeminal ganglion. Fast blue was injected into 12 sites of the rat orofacial regions, and ganglion cells were retrogradely labeled. The labeled trigeminal ganglia were cleared by modified 3DISCO, imaged with confocal laser-scanning microscopy, and reconstructed in 3D. Histograms of the major axes of the fast blue-positive somata revealed that the peak major axes of the cells innervating the skin/mucosa were smaller than those of cells innervating the deep structures. Ganglion cells innervating the ophthalmic, maxillary, and mandibular divisions were distributed in the anterodorsal, central, and posterolateral portions of the trigeminal ganglion, respectively, with considerable overlap in the border region. The intermingling in the distribution of ganglion cells within each division was also high, in particular, within the mandibular division. Specifically, intermingling was observed in combinations of tongue and masseter/temporal muscles, maxillary/mandibular molars and masseter/temporal muscles, and tongue and mandibular molars. Double retrograde labeling confirmed that some ganglion cells innervating these combinations were closely apposed. Our data provide essential information for understanding the function of ganglion cell-cell interactions via satellite cells., (© 2024 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Aims: Itch is an unpleasant sensation that severely impacts the patient's quality of life. Recent studies revealed that the G protein-coupled estrogen receptor (GPER) may play a crucial role in the regulation of pain and itch perception. However, the contribution of the GPER in primary sensory neurons to the regulation of itch perception remains elusive. This study aimed to investigate whether and how the GPER participates in the regulation of itch perception in the trigeminal ganglion (TG)., Methods and Results: Immunofluorescence staining results showed that GPER-positive (GPER + ) neurons of the TG were activated in both acute and chronic itch. Behavioral data indicated that the chemogenetic activation of GPER + neurons of the TG of Gper-Cre mice abrogated scratching behaviors evoked by acute and chronic itch. Conversely, the chemogenetic inhibition of GPER + neurons resulted in increased itch responses. Furthermore, the GPER expression and function were both upregulated in the TG of the dry skin-induced chronic itch mouse model. Pharmacological inhibition of GPER (or Gper deficiency) markedly increased acute and chronic itch-related scratching behaviors in mouse. Calcium imaging assays further revealed that Gper deficiency in TG neurons led to a marked increase in the calcium responses evoked by agonists of the transient receptor potential ankyrin A1 (TRPA1) and transient receptor potential vanilloid V1 (TRPV1)., Conclusion: Our findings demonstrated that the GPER of TG neurons is involved in the regulation of acute and chronic itch perception, by modulating the function of TRPA1 and TRPV1. This study provides new insights into peripheral itch sensory signal processing mechanisms and offers new targets for future clinical antipruritic therapy., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Some γ-glutamyl peptides including glutathione (γ-Glu-Cys-Gly) and γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly= γ-EVG) are reported to increase the intensity of basic tastes, such as salty, sweet, and umami, although they have no taste themselves at tested concentrations. The mechanism of action of γ-glutamyl peptides is not clearly understood, but the calcium sensing receptor (CaSR) may be involved. Glutathione and γ-EVG enhance the pungency of some spices, and the present study investigated the effects of γ-EVG on the responses of trigeminal ganglion (TG) cells to thermosensitiveTRP channel agonists. Single-cell RT-PCR revealed that most CaSR-expressing cells co-expressed TRPV1 (sensitive to capsaicin) and TRPA1 (sensitive to allyl isothiocyanate= AITC). Intracellular Ca2+ imaging showed that pretreatment with γ-EVG excited 7% of trigeminal ganglion (TG) cells and increased the amplitude of their responses to AITC, but not to capsaicin or menthol. The enhancing effect of γ-EVG was prevented by a CaSR inhibitor. The results indicate that γ-EVG increases AITC pungency by activating a subset of trigeminal ganglion cells that co-express CaSR and TRPA1.

Background: Primary neuronal cultures are used to elucidate cellular and molecular mechanisms involved in disease pathology and modulation by pharmaceuticals and nutraceuticals, and to identify novel therapeutic targets. However, preparation of primary neuronal cultures from rodent embryos is labor-intensive, and it can be difficult to produce high-quality consistent cultures. To overcome these issues, cryopreservation can be used to obtain standardized, high-quality stocks of neuronal cultures., New Method: In this study, we present a simplified cryopreservation method for rodent primary trigeminal ganglion neurons and glia from Sprague-Dawley neonates, using a 90:10 (v/v) fetal bovine serum/dimethyl sulfoxide cell freezing medium., Results: Cryopreserved trigeminal ganglion cells stored for up to one year in liquid nitrogen exhibited similar neuronal and glial cell morphology to fresh cultures and retained high cell viability. Proteins implicated in inflammation and pain signaling were expressed in agreement with the reported subcellular localization. Additionally, both neurons and glial cells exhibited an increase in intracellular calcium levels in response to a depolarizing stimulus. Cryopreserved cells were also transiently transfected with reporter genes., Comparison With Existing Methods: Our method is simple, does not require special reagents or equipment, will save time and money, increase flexibility in study design, and produce consistent cultures., Conclusions: This method for the preparation and cryopreservation of trigeminal ganglia results in primary cultures of neurons and glia similar in viability and morphology to fresh preparations that could be utilized for biochemical, cellular, and molecular studies, increase reproducibility, and save laboratory resources., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Genetically encoded calcium indicators (GECIs) enable imaging techniques to monitor changes in intracellular calcium in targeted cell populations. Their large signal-to-noise ratio makes GECIs a powerful tool for detecting stimulus-evoked activity in sensory neurons. GECIs facilitate population-level analysis of stimulus encoding with the number of neurons that can be studied simultaneously. This population encoding is most appropriately done in vivo. Dorsal root ganglia (DRG), which house the soma of sensory neurons innervating somatic and visceral structures below the neck, are used most extensively for in vivo imaging because these structures are accessed relatively easily. More recently, this technique was used in mice to study sensory neurons in the trigeminal ganglion (TG) that innervate oral and craniofacial structures. There are many reasons to study TG in addition to DRG, including the long list of pain syndromes specific to oral and craniofacial structures that appear to reflect changes in sensory neuron activity, such as trigeminal neuralgia. Mice are used most extensively in the study of DRG and TG neurons because of the availability of genetic tools. However, with differences in size, ease of handling, and potentially important species differences, there are reasons to study rat rather than mouse TG neurons. Thus, we developed an approach for imaging rat TG neurons in vivo. We injected neonatal pups (p2) intraperitoneally with an AAV encoding GCaMP6s, resulting in >90% infection of both TG and DRG neurons. TG was visualized in the adult following craniotomy and decortication, and changes in GCaMP6s fluorescence were monitored in TG neurons following stimulation of mandibular and maxillary regions of the face. We confirmed that increases in fluorescence were stimulus-evoked with peripheral nerve block. While this approach has many potential uses, we are using it to characterize the subpopulation(s) of TG neurons changed following peripheral nerve injury.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of NSAID-based pain relief is the inhibition of cyclooxygenase-2, several NSAIDs also modulate other molecular targets related to nociceptive transmission such as voltage-gated Na + channels. In the present study, we examined the effects of NSAIDs on persistent Na + current (I NaP ) mediated by tetrodotoxin-resistant (TTX-R) Na + channels in small-to medium-sized trigeminal ganglion neurons using a whole-cell patch-clamp technique. At clinically relevant concentrations, all propionic acid derivatives tested (ibuprofen, naproxen, fenoprofen, and flurbiprofen) preferentially inhibited the TTX-R I NaP . The inhibition was more potent at acidic extracellular pH (pH 6.5) than at normal pH (pH 7.4). Other NSAIDs, such as ketorolac, piroxicam, and aspirin, had a negligible effect on the TTX-R I NaP . Ibuprofen both accelerated the onset of inactivation and retarded the recovery from inactivation of TTX-R Na + channels at acidic extracellular pH. However, all NSAIDs tested in this study had minor effects on voltage-gated K + currents, as well as hyperpolarization-activated and cyclic nucleotide-gated cation currents, at both acidic and normal extracellular pH. Under current-clamp conditions, ibuprofen decreased the number of action potentials elicited by depolarizing current stimuli at acidic (pH 6.5) extracellular pH. Considering that extracellular pH falls as low as 5.5 in inflamed tissues, TTX-R I NaP inhibition could be a mechanism by which ibuprofen and propionic acid derivative NSAIDs modulate inflammatory pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract Background Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. Methods A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. Results Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. Conclusions LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression. Graphical Abstract The up-regulated lncRNA Anxa10-203 in the trigeminal ganglion of CCI-ION mice interacts with DHX30 to contribute to the excitability of TG neurons and orofacial pain by enhancing Mc1r mRNA stability.

Cannabinoid receptors are expressed in human and animal trigeminal sensory neurons; however, the expression in the equine trigeminal ganglion is unknown. Ten trigeminal ganglia from five horses were collected post-mortem from an abattoir. The expression of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and the cannabinoid-related receptors like transient receptor potential vanilloid type 1 (TRPV1), peroxisome proliferator-activated receptor gamma (PPARɣ), and G protein-related receptor 55 (GPR55) in the trigeminal ganglia (TG) of the horse were studied, using immunofluorescence on cryosections and formalin-fixed paraffin-embedded (FFPE) sections. Neurons and glial cells were identified using fluorescent Nissl staining NeuroTrace ® and an antibody directed against the glial marker glial fibrillary acidic protein (GFAP), respectively. Macrophages were identified by means of an antibody directed against the macrophages/microglia marker ionized calcium-binding adapter molecule 1 (IBA1). The protein expression of CB1R, CB2R, TRPV1, and PPARɣ was found in the majority of TG neurons in both cryosections and FFPE sections. The expression of GPR55 immunoreactivity was mainly detectable in FFPE sections, with expression in the majority of sensory neurons. Some receptors were also observed in glial cells (CB2R, TRPV1, PPARγ, and GPR55) and inflammatory cells (PPARγ and GPR55). These results support further investigation of such receptors in disorders of equine trigeminal neuronal excitability.

We previously demonstrated that experimental traumatic occlusion (ETO) induces a long-lasting nociceptive response. These findings were associated with altered neuronal patterns and suggestive satellite glial cell activation. This study aimed to elucidate the activation of satellite glial cells following ETO in the trigeminal ganglion. Moreover, we explored the involvement of resident and infiltrating cells in trigeminal ganglion in ETO. Finally, we investigated the overexpression of purinergic signaling and the CX3CL1/CX3CR1 axis. RT-qPCR and electrophoresis showed overexpression of GFAP in the trigeminal ganglion (TG), and immunohistochemistry corroborated these findings, demonstrating SGCs activation. ELISA reveals enhanced levels of TNF-α and IL-1β in TG after 28 d of ETO. In trigeminal ganglia, ETO groups improved the release of CX3CL1, and immunohistochemistry showed higher CX3CR1 + -immunoreactive cells in ETO groups. Immunohistochemistry and electrophoresis of the P2X7 receptor were found in ETO groups. The mRNA levels of IBA1 are upregulated in the 0.7-mm ETO group, while immunohistochemistry showed higher IBA1 + -immunoreactive cells in both ETO groups. The expression of CD68 by electrophoresis and immunohistochemistry was observed in the ETO groups. For last, ELISA revealed increased levels of IL-6, IL-12, and CCL2 in the TG of ETO groups. Furthermore, the mRNA expression revealed augmented transcription factors and cytokines associated with lymphocyte activation, such as RORγt, IL-17, Tbet, IFNγ, FOXP3, and IL-10. The findings of this study suggested that ETO activates SGCs in TG, and purinergic signaling and CX3CL1/CX3CR1 axis were upregulated. We uncovered the involvement of a distinct subtype of macrophages, named sensory neuron-associated macrophage activation (sNMAs), and detected an expanded number of infiltrated macrophages onto TG. These findings indicate that ETO induces chronic/persistent immune response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Trigeminal ganglia (TG) are bilateral collections of cell bodies from the first-order pseudounipolar neurons in each trigeminal nerve. Branches of the internal carotid artery (ICA), middle meningeal artery (MMA), accessory meningeal artery (AMA), and superior cerebellar artery (SCA) have been known to supply the TG, but information about the prevalence and patterns of these vessels supplying the TG is limited despite their important clinical relevance to basicranial surgeries. The objective of this study is to investigate the arterial sources and supply patterns to the TG and discuss their clinical implications. Methods: Gross arterial sources and supply patterns were examined on 139 TG from 90 embalmed human cadavers from ethically approved anatomical donor programs. Select specimens were photographed, and color replacement was utilized to aid structure identification. Vascular histology was examined with light microscopy and photographed on one specimen for methods validation. Results: One hundred and one TG (72.7%) received arterial supply from a single source: 71 (51.1%) from ICA, 18 (12.9%) from AMA, and 12 (8.6%) from MMA. Thirty-seven TG (26.6%) exhibited two distinct arterial sources from ICA, AMA, or MMA in either anastomotic (n = 25; 18.0%) or dual-independent (n = 12; 8.6%) patterns. One TG (0.7%) received supply from ICA, AMA, and MMA in a complex pattern. No gross arterial supply from SCA was found. Conclusions: The TG is predominantly supplied by ICA (prevalence = 76.3%), though AMA and MMA also represent considerable contributions (31.7% and 20.1%, respectively) in various supply patterns. The TG arterial sources and supply patterns reported in this study should be considered when deliberating treatment of meningiomas, schwannomas, and dural arteriovenous fistulas within and around Meckel's cave.

Corneal nerves originate from the ophthalmic branch of the trigeminal nerve, which enters the cornea at the limbus radially from all directions toward the central cornea. The cell bodies of the sensory neurons of trigeminal nerve are located in the trigeminal ganglion (TG), while the axons are extended into the three divisions, including ophthalmic branch that supplies corneal nerves. Study of primary neuronal cultures established from the TG fibers can therefore provide a knowledge basis for corneal nerve biology and potentially be developed as an in vitro platform for drug testing. However, setting up primary neuron cultures from animal TG has been dubious with inconsistency among laboratories due to a lack of efficient isolation protocol, resulting in low yield and heterogenous cultures. In this study, we used a combined enzymatic digestion with collagenase and TrypLE to dissociate mouse TG while preserving nerve cell viability. A subsequent discontinuous Percoll density gradient followed by mitotic inhibitor treatment effectively diminished the contamination of non-neuronal cells. Using this method, we reproducibly generated high yield and homogenous primary TG neuron cultures. Similar efficiency of nerve cell isolation and culture was further obtained for TG tissue cryopreserved for short (1 week) and long duration (3 months), compared to freshly isolated tissues. In conclusion, this optimized protocol shows a promising potential to standardize TG nerve culture and generate a high-quality corneal nerve model for drug testing and neurotoxicity studies.

The P2Y 2 receptor agonist, diquafosol sodium, is commonly used to treat the signs and symptoms of dry eye disease (DE) patients. Although diquafosol improves tear film stability, the neural mechanisms underlying the reduction in ocular pain are not well defined. This study determined if repeated application of diquafosol reduces the sensitization of nociceptive neurons in the lower trigeminal brainstem nuclear complex (TBNC) via peripheral P2Y 2 mechanisms in a rat model for DE. Diquafosol was applied to the ocular surface daily for 28 days, starting at day 0 or day 14, after exorbital gland removal. The number of eyeblinks, P2Y 2 -immunoreactive neurons in the trigeminal ganglion (TG), and correlates of TBNC neural excitability (i.e., cFos protein and phosphorylated extracellular signal-regulated kinase (pERK) expression) were assessed in male rats. Diquafosol increased spontaneous tear volume and reduced the number of ocular surface-evoked eyeblinks in DE rats. Fluorogold-labeled TG neurons that supply the cornea expressed P2Y 2 . The number of P2Y 2 -immunoreactive neurons was increased in DE rats and suppressed by diquafosol. Diquafosol also reduced the number of cFos- and pERK-immunoreactive neurons in the TBNC in DE rats. These findings suggest that diquafosol, regardless of late-phase treatment, relieves ocular nociception in DE by reducing peripheral P2Y 2 expression., (Copyright © 2023 Elsevier Ltd and Japan Neuroscience Society. All rights reserved.)

Mengzhen Xu,1 Jin Liu,1 Hui Zhang,2 Ruiting Li,3 Junni Wei1 1School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pain Management, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pain Management, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Hui Zhang, Department of Pain Management, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China, Tel +86 351 13934043126, Fax + 0351-4639114, Email hzhang1974@163.comPurpose: To investigate the clinical outcome of trigeminal ganglion electrical stimulation for the treatment of trigeminal postherpetic neuralgia (TPHN).Patients and Methods: A retrospective analysis of clinical data was performed on six patients who suffered from severe postherpetic neuralgia involving the trigeminal nerve maxillary and mandibular branch. They were admitted under the Pain Management Department of the First Hospital of Shanxi Medical University from July 2022 to February 2023 and underwent trigeminal ganglion electrical stimulation therapy. Visual analogue scale (VAS) scores, pregabalin dosage, pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were recorded before treatment, as well as after treatment at 1, 4, 8, 12, and 24-week. Adverse reactions related to the treatment were also documented.Results: After trigeminal ganglion electrical stimulation therapy, the VAS scores, PSQI scores, anxiety scores, depression scores, and pregabalin dosage of six patients showed significant reductions at 1, 4, 8, 12, and 24 weeks. (P < 0.05). No serious adverse reactions occurred in any of the patients.Conclusion: Trigeminal ganglion electrical stimulation effectively relieved postherpetic neuralgia in the distribution areas of the trigeminal nerve 2 and 3 branches, reduced the dosage of analgesics, improved the quality of sleep, and alleviated anxiety and depression symptoms in patients. Our data suggested that It was a safe and effective clinical.Keywords: trigeminal postherpetic neuralgia, trigeminal ganglion stimulation, therapy, efficacy

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1β, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1β within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitogen activated protein kinase interacting kinases (MNK) 1 and 2 are serine/threonine protein kinases that play an important role in translation of mRNAs through their phosphorylation of the RNA 5'-cap binding protein, eukaryotic translation initiation factor (eIF) 4E. These kinases are downstream targets for mitogen activated protein kinases (MAPKs), extracellular activity regulated protein kinase (ERK) and p38. MNKs have been implicated in the sensitization of peripheral nociceptors of the dorsal root and trigeminal ganglion (DRG and TG) using transgenic mouse lines and through the use of specific inhibitors of MNK1 and MNK2. While specific knockout of the Mknk1 gene suggests that it is the key isoform for regulation of nociceptor excitability and nociceptive behaviors in mice, both MKNK1 and MKNK2 genes are expressed in the DRG and TG of mice and humans based on RNA sequencing experiments. Single cell sequencing in mice suggests that Mknk1 and Mknk2 may be expressed in different populations of nociceptors. We sought to characterize mRNA expression in human DRG and TG (N = 3 ganglia for both DRG and TG) for both MNK1 and MNK2. Our results show that both genes are expressed by nearly all neurons in both human ganglia with expression in other cell types as well. Our findings provide evidence that MNK1 and MNK2 are expressed by human nociceptors of males and females and suggest that efforts to pharmacologically target MNKs for pain would likely be translatable due its conserved expression in both species., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy., Purpose: Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective., Methods/results: After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca 2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca 2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect., Conclusion: This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Background:  Increased intraocular pressure (IOP) likely secondary to an activated oculo-trigeminal reflex network is an important issue following subarachnoid hemorrhage (SAH). The relationship between the IOP and trigeminal ganglion (TGG) following experimental SAH was investigated in this study., Methods:  Twenty-three rabbits were used in this study. Five rabbits ( n  = 5) were used as the control group, another 5 as the sham group ( n  = 5), and the remaining 13 ( n  = 13) as the study group. The study group was further divided into two groups of animals with mild ( n  = 6) and severe ( n  = 7) TGG degeneration. The IOP values were recorded. After 2 weeks, the animals were decapitated. The mean degenerated neuron density of TGGs was estimated by stereological methods and analyzed statistically., Results:  The average IOP values were 11.85, 14.12, and 21.45 mm Hg in the control ( n  = 5), sham ( n  = 5), and study ( n  = 13) groups, respectively. The mean degenerated neuron density was 34, 237, and 3,165 mm 3 in the control, sham, and study groups, respectively., Conclusion:  According to the findings of this study, the experimental SAH leads to changes in IOP by affecting the TGG. By predicting and preventing IOP elevation in the setting of SAH, our findings will shed light on secondary sequelae such as glaucoma and irreversible blindness., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Trigeminal neuralgia (TN) is the most common excruciating cranial neuralgia in the elderly population. Radiofrequency thermocoagulation (RFT) of the trigeminal ganglion is an alternative treatment for medically intractable patients with TN. RFT cannula tip position is an important issue since it is related to treatment outcome and patient safety., Objectives: The purpose of this study was to evaluate the fluoroscopic position of a cannula tip when a maximal stimulation-induced paresthesia was obtained and the treatment outcome using a Barrow Neurological Institute (BNI) pain scale., Study Design: Retrospective analysis., Setting: An interventional pain management practice in South Korea., Methods: The final cannula tip position obtained under maximal electrical stimulation of the face was analyzed using previously saved fluoroscopic images., Results: The cannula tip was located exactly in the clival line in 10 patients (29.4%) with maxillary division (V2) TN. There were 24 patients of V2 TN (70.5% ) in whom the cannula tip was located below the clival line. Over 50% of cannula tips were located at -11 mm to -15 mm below the clival line in mandibular division (V3) TN. Forty-four patients (83%) who received RFT in the trigeminal ganglion demonstrated BNI I or II., Limitations: The number of patients with V3 TN was smaller than that of V2 TN. Only short-term efficacy was evaluated, but not long-term efficacy or recurrence rate of facial pain., Conclusions: Nearly 70% of patients in V2 TN and all patients in V3 TN, the cannula tip was positioned below the clival line. RFT of the trigeminal ganglion showed a successful treatment outcome with BNI I or II in 83% of patients.

Abstract Background Adipokines, including adiponectin, are implicated in nociceptive pain; however, the underlying cellular and molecular mechanisms remain unknown. Methods Using electrophysiological recording, immunostaining, molecular biological approaches and animal behaviour tests, we elucidated a pivotal role of adiponectin in regulating membrane excitability and pain sensitivity by manipulating Cav3.2 channels in trigeminal ganglion (TG) neurons. Results Adiponectin enhanced T-type Ca2+ channel currents (I T) in TG neurons through the activation of adiponectin receptor 1 (adipoR1) but independently of heterotrimeric G protein-mediated signaling. Coimmunoprecipitation revealed a physical association between AdipoR1 and casein kinase II alpha-subunits (CK2α) in the TG, and inhibiting CK2 activity by chemical inhibitor or siRNA targeting CK2α prevented the adiponectin-induced I T response. Adiponectin significantly activated protein kinase C (PKC), and this effect was abrogated by CK2α knockdown. Adiponectin increased the membrane abundance of PKC beta1 (PKCβ1). Blocking PKCβ1 pharmacologically or genetically abrogated the adiponectin-induced I T increase. In heterologous expression systems, activation of adipoR1 induced a selective enhancement of Cav3.2 channel currents, dependent on PKCβ1 signaling. Functionally, adiponectin increased TG neuronal excitability and induced mechanical pain hypersensitivity, both attenuated by T-type channel blockade. In a trigeminal neuralgia model induced by chronic constriction injury of infraorbital nerve, blockade of adipoR1 signaling suppressed mechanical allodynia, which was prevented by silencing Cav3.2. Conclusion Our study elucidates a novel signaling cascade wherein adiponectin stimulates TG Cav3.2 channels via adipoR1 coupled to a novel CK2α-dependent PKCβ1. This process induces neuronal hyperexcitability and pain hypersensitivity. Insight into adipoR-Cav3.2 signaling in sensory neurons provides attractive targets for pain treatment.

Objective: Although macrophage polarisation in the trigeminal ganglion (TG) is crucial in orofacial pain hypersensitivity, the effect of ageing-related changes and their involvement in intra-oral nociception remains unclear. We assessed the effect of ageing-related macrophage polarisation in TG on intra-oral mechanical pain hypersensitivity following palatal mucosal incision using senescence-accelerated mice (SAM)-prone8 (SAMP8) and SAM-resistant 1 (SAMR1)., Materials and Methods: Mechanical head-withdrawal reflex threshold (MHWRT) of the palatal mucosa was measured for 21 days after palatal mucosal incision. On days 3 and 14, the abundance of Iba-1-immunoreactive (IR) cells, CD11c-IR cells (pro-inflammatory macrophages (M1)), C-C motif chemokine ligand 2 (CCL2)-IR M1-macrophages, CD206-IR cells (anti-inflammatory macrophages (M2)) and transforming growth factor-β (TGF-β)-IR M2-macrophages in the TG was analysed. The effect of continuous intra-TG administration of CCL2-neutralising antibody or recombinant-CCL2 on MHWRT was examined., Results: Incision-induced decrease in MHWRT was enhanced in SAMP8 compared with that in SAMR1. On days 3 and 14, the number of CCL2-IR M1-macrophages in TG was increased in SAMP8 compared with that in SAMR1. CCL2-neutralising antibody suppressed, whereas recombinant-CCL2 increased pain hypersensitivity in SAMP8., Conclusions: Mechanical pain hypersensitivity after oral mucosal injury is potentiated and sustained by age-related enhancement of CCL2 signalling via M1-macrophage hyperactivation in TG., (© 2024 John Wiley & Sons Ltd.)

Background: The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure. We performed RNA sequencing on the forming chick trigeminal ganglion and identified Elongator acetyltransferase complex subunit 1 (Elp1) for further study. Mutations in ELP1 cause familial dysautonomia (FD), a fatal disorder characterized by the presence of smaller trigeminal nerves and sensory deficits. While Elp1 has established roles in neurogenesis, its function in placode cells during trigeminal gangliogenesis has not been investigated., Results: To this end, we used morpholinos to deplete Elp1 from chick trigeminal placode cells. Elp1 knockdown decreased trigeminal ganglion size and led to aberrant innervation of the eye by placode-derived neurons. Trigeminal nerve branches also appeared to exhibit reduced axon outgrowth to target tissues., Conclusions: These findings reveal a new role for Elp1 in placode-derived neurons during chick trigeminal ganglion development. These results have potential high significance to provide new insights into trigeminal ganglion development and the etiology of FD., (© 2024 The Author(s). Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Objective: We explored the feasibility of single-division puncture in the ophthalmic division, maxillary division, and mandibular division of the trigeminal ganglion intumescentia (TGI) and the feasibility of radiofrequency treatment of trigeminal neuralgia., Methods: According to the previous anatomical image studies, 3D Slicer software was used to analyze the CT images of the patients. The trigeminal ganglion fossa (TGF) was used as the imaging sign. TGI was identified in the sagittal plane along the fiber. The puncture path starts from the TGI center-foramen ovale line, extending outward to the epidermis as the needle insertion point, and extending inward to the division boundary. For lateral puncture, which is blocked by the mandible, the positions of closed mouth, open mouth, and over-open mouth were used. Multiple targets were generated using straight electrodes and curved electrodes to achieve full coverage of TGI. According to the preoperative design, general anesthesia surgery was performed. Xper CT was used for imaging, and the puncture was guided by Xper Guide. Radiofrequency treatment of TGI was conducted., Results: In total, 45 patients with trigeminal neuralgia underwent 50 single-division TGI punctures. The procedure was smooth and the compliance with the design was good. Continuous radiofrequency (CRF) was performed, the VAS scores were 25 times at 70°C, 19 times at 65°C, two times at 60°C, and two times at 50°C (both in the ophthalmic division). Pulsed radiofrequency (PRF) was conducted two times. Within 24 h after the procedure, the VAS scores were all 0. From 1 to 7 days after the procedure, pain recurrence was found in three cases, of whom two cases received pulsed radiofrequency treatment. Patients were followed up for 1-24 months and there were no recurrence. After continuous radiofrequency at 65-70°C, the moderate tactile loss was observed, and nearly half of the patients had food residues on the surgical side after 6 months. After continuous radiofrequency at 60°C, there was mild tactile loss and no food residue. The tactile sensation was slightly decreased after continuous radiofrequency at 50°C, and the tactile sensation was normal the next day., Conclusion: Trigeminal ganglion intumescentia single-division radiofrequency is effective and feasible for the treatment of trigeminal neuralgia., (© 2023 World Institute of Pain.)