Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

Rodent MrgC receptor (Mas-related G-protein-coupled receptor subtype C) shares 65% sequence homology and similarities in terms of expression pattern and binding profile with human Mas-related gene X receptor 1 (hMrgX1). Therefore, researchers generally explore the role of hMrgX1 by studying the function of MrgC receptor. Murine MrgC receptor is uniquely expressed in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia (TG), which is closely related to the transmission process of pain. This review summarizes the analgesic effects of intrathecal activation of MrgC receptors in pathological pain and morphine tolerance.
Animals ; Drug Tolerance ; Ganglia, Spinal ; Humans ; Mice ; Morphine ; pharmacology ; Pain ; Peptide Fragments ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; physiology ; Trigeminal Ganglion

Trigeminal neuralgia is caused by compression of trigeminal nerve root and it leads to demyelination gradually. It was almost idiopathic and occurred unexpected. The upper cervical spinal cord contains the spinal trigeminal tract and nucleus. Fibers with cell bodies in the trigeminal ganglion enter in the upper pons and descend caudally to C2 level. We experienced a rare patient with facial pain, which was paroxysmal attack with severe pain after a clear event, cervical spinal injury (C2). So, this case reminds us of a possible cause of trigeminal neuralgia after a trauma of the head and neck.
Cell Body ; Cervical Cord ; Demyelinating Diseases ; Facial Pain ; Head ; Humans ; Neck ; Odontoid Process ; Pons ; Spinal Cord ; Spinal Injuries ; Trigeminal Ganglion ; Trigeminal Nerve ; Trigeminal Neuralgia

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.
Cell Communication ; Cervical Cord ; Facial Pain ; Inflammation ; Macrophages ; Neurons ; Nociceptors ; Trigeminal Ganglion ; Trigeminal Nerve ; Trigeminal Nerve Injuries ; Trigeminal Nucleus, Spinal

Orthodontic pain that is induced by tooth movement is an important sequela of orthodontic treatment and has a significant effect on patient quality of life. Studies have shown that the high expression of transient receptor potential vanilloid 1 (TRPV1) in trigeminal ganglions plays a vital role in the transmission and modulation of orofacial pain. However, little is known about the role of TRPV1 in orthodontic pain. In this study, male Sprague-Dawley rats were randomly assigned to six groups to study the role of TRPV1 in the modulation of tooth-movement pain. The expression levels of TRPV1 mRNA and protein were determined by real-time PCR and western blot, respectively. Moreover, pain levels were assessed using the rat grimace scale (RGS). The role of TRPV1 in modulating tooth-movement pain was examined by injecting a TRPV1 antagonist into the trigeminal ganglia of rats. A lentivirus containing a TRPV1 shRNA sequence was constructed and transduced into the rats' trigeminal ganglia. The results showed that the expression levels of TRPV1 protein and mRNA were elevated following tooth-movement pain. Pain levels increased rapidly on the 1 day, peaked on the 3 day and returned to baseline on the 14 day. The TRPV1 antagonist significantly reduced tooth-movement pain. The lentivirus containing a TRPV1 shRNA sequence was able to inhibit the expression of TRPV1 and relieved tooth-movement pain. In conclusion, TRPV1-based gene therapy may be a treatment strategy for the relief of orthodontic pain.
Animals ; Calcitonin Gene-Related Peptide ; Genetic Therapy ; Male ; Molar ; Pain ; Quality of Life ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels ; Tooth Movement Techniques ; Trigeminal Ganglion

OBJECTIVE: To evaluate the accuracy and feasibility of a custom robot system guided by optical navigation for needle puncture on trigeminal gasserian ganglion. METHODS: A synthetic human skull model was used, with plasticine placed around the skull base to imitate the human soft tissue. Cone beam CT (CBCT) scanning was performed before the operation. With image data transferred to the graphical user interface of the computer workstation, the oval foramen was selected as the target and the "skin entry point" was also determined by the surgeon on the surgical planning software. Thus the needle trajectory was eventually planned. The skull model was fixed firmly to the trial table with a head clamp and relative size of the trial table was the same as a standard operating table. Following point-based registration, the data were sent to the robot control unit. Only after the surgeon's confirmation, the needle was automatically inserted into the intended target by the robot guided by optical navigation. When the procedure was completed, the instantaneous data of the needle tip orientation acquired by navigation system was sent back to the computer workstation for accuracy verification by calculating the geometric distance between the needle tip and the planning target after matrix transformation. Subsequently, after the needle had been released, CBCT scanning was also acquired to make image fusion of the preoperative skull and the postoperative skull. The data of the needle tip orientation was acquired on the postoperative image and the accuracy was re-verified by calculating the geometric distance between the needle tip and the planning target after matrix transformation. IBM SPSS Statistics 20 was used for statistical analysis and the paired t-test was used to compare the differences in the accuracy measured by the intraoperative navigation and postoperative image fusion. RESULTS: All 20 interventions were successfully located in oval foramen at the first needle insertion. The mean deviation of the needle tip was (0.56±0.07) mm (measured by the navigation system) and (1.49±0.14) mm (measured by the image fusion), respectively (P<0.001). CONCLUSION The experimental results show the robot system is efficient and reliable. The navigation accuracy is one of the most significant factors in robotic procedures.
Humans ; Needles ; Robotic Surgical Procedures ; Robotics ; Surgery, Computer-Assisted ; Trigeminal Ganglion

Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery. Stellate ganglion block (SGB) is a nerve block method that is used for treatment of neuropathic pain in the head, neck and upper extremities, especially trigeminal neuralgia, postherpetic neuralgia and complex regional pain syndrome. SGB can modulate and stabilize the sympathetic nervous system, which prevents it from overexcitation and improves symptoms of syncope. The authors report a patient who was treated for pain and edema of both upper extremities with SGB, then showed improvement in recurrent syncope followed by chest pain and overall quality of life.
Chest Pain ; Edema ; Head ; Humans ; Methods ; Neck ; Nerve Block ; Neuralgia ; Neuralgia, Postherpetic ; Quality of Life ; Stellate Ganglion ; Sympathetic Nervous System ; Syncope ; Thorax ; Trigeminal Neuralgia ; Unconsciousness ; Upper Extremity

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.
Analgesia ; Animals ; Constriction ; Humans ; Hyperalgesia* ; Male ; Neuralgia ; Neurons ; Rats* ; Rats, Sprague-Dawley ; Sodium Channels ; Trigeminal Ganglion ; Up-Regulation ; Voltage-Gated Sodium Channels

Migraine is a neurological disorder characterized by recurrent and disabling severe headaches. Although several anticonvulsant drugs that block voltage-dependent Na⁺ channels are widely used for migraine, far less is known about the therapeutic actions of carbamazepine on migraine. In the present study, therefore, we characterized the effects of carbamazepine on tetrodotoxin-resistant (TTX-R) Na⁺ channels in acutely isolated rat dural afferent neurons, which were identified by the fluorescent dye DiI. The TTX-R Na⁺ currents were measured in medium-sized DiIpositive neurons using the whole-cell patch clamp technique in the voltage-clamp mode. While carbamazepine had little effect on the peak amplitude of transient Na⁺ currents, it strongly inhibited steady-state currents of transient as well as persistent Na⁺ currents in a concentration-dependent manner. Carbamazepine had only minor effects on the voltage-activation relationship, the voltage-inactivation relationship, and the use-dependent inhibition of TTX-R Na⁺ channels. However, carbamazepine changed the inactivation kinetics of TTX-R Na⁺ channels, significantly accelerating the development of inactivation and delaying the recovery from inactivation. In the current-clamp mode, carbamazepine decreased the number of action potentials without changing the action potential threshold. Given that the sensitization of dural afferent neurons by inflammatory mediators triggers acute migraine headaches and that inflammatory mediators potentiate TTX-R Na⁺ currents, the present results suggest that carbamazepine may be useful for the treatment of migraine headaches.
Action Potentials ; Animals ; Anticonvulsants ; Carbamazepine* ; Headache ; Kinetics ; Migraine Disorders ; Nervous System Diseases ; Neurons* ; Neurons, Afferent ; Rats ; Sodium Channels ; Trigeminal Ganglion*

Cranial Fossa, Posterior ; Cranial Nerve Neoplasms ; diagnosis ; pathology ; Ganglioneuroma ; diagnosis ; pathology ; Humans ; Male ; Middle Aged ; Skull Base Neoplasms ; diagnosis ; pathology ; Trigeminal Ganglion