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Frontiers in Molecular Neuroscience 2024[This corrects the article DOI: 10.3389/fnmol.2023.1083850.].
[This corrects the article DOI: 10.3389/fnmol.2023.1083850.].
PubMed: 38751714
DOI: 10.3389/fnmol.2024.1417118 -
BMC Oral Health May 2024Patients who suffer from myofascial orofacial pain could affect their quality of life deeply. The pathogenesis of pain is still unclear. Our objective was to assess...
Patients who suffer from myofascial orofacial pain could affect their quality of life deeply. The pathogenesis of pain is still unclear. Our objective was to assess Whether Voltage-gated calcium channel αδ-1(Cavα2δ-1) is related to myofascial orofacial pain. Rats were divided into the masseter tendon ligation group and the sham group. Compared with the sham group, the mechanical pain threshold of the masseter tendon ligation group was reduced on the 4th, 7th, 10th and 14th day after operation(P < 0.05). On the 14th day after operation, Cavα2δ-1 mRNA expression levels in trigeminal ganglion (TG) and the trigeminal spinal subnucleus caudalis and C1-C2 spinal cervical dorsal horn (Vc/C) of the masseter tendon ligation group were increased (P=0.021, P=0.012). Rats were divided into three groups. On the 4th day after ligating the superficial tendon of the left masseter muscle of the rats, 10 ul Cavα2δ-1 antisense oligonucleotide, 10 ul Cavα2δ-1 mismatched oligonucleotides and 10 ul normal saline was separately injected into the left masseter muscle of rats in Cavα2δ-1 antisense oligonucleotide group, Cavα2δ-1 mismatched oligonucleotides group and normal saline control group twice a day for 4 days. The mechanical pain threshold of the Cavα2δ-1 antisense oligonucleotides group was higher than Cavα2δ-1 mismatched oligonucleotides group on the 7th and 10th day after operation (P < 0.01). After PC12 cells were treated with lipopolysaccharide, Cavα2δ-1 mRNA expression level increased (P < 0.001). Cavα2δ-1 may be involved in the occurrence and development in myofascial orofacial pain.
Topics: Animals; Rats; Masseter Muscle; Male; Rats, Sprague-Dawley; Calcium Channels; Trigeminal Ganglion; Pain Threshold; Facial Pain; Spinal Cord Dorsal Horn; Oligonucleotides, Antisense; Myofascial Pain Syndromes; RNA, Messenger; Calcium Channels, L-Type
PubMed: 38735923
DOI: 10.1186/s12903-024-04338-y -
Acta Neurochirurgica May 2024Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to... (Review)
Review
Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to microvascular decompression (idiopathic or secondary TNs). Introduced through the foramen ovale, behind the trigemnial ganglion in the triangular plexus, the needle is navigated by radiology and neurophysiological testing to target the retrogasserian fibers corresponding to the trigger zone. Heating to 55-75 °C can achieve hypoesthesia without anaesthesia dolorosa if properly controlled. Depth of anaesthesia varies dynamically sedation for cannulation and lesioning, and awareness during neurophysiologic navigation. Proper technique ensures long-lasting results in more than 75% of patients.
Topics: Trigeminal Neuralgia; Humans; Electrocoagulation; Trigeminal Nerve; Foramen Ovale; Trigeminal Ganglion; Microvascular Decompression Surgery; Treatment Outcome
PubMed: 38727725
DOI: 10.1007/s00701-024-06074-2 -
Biochemical and Biophysical Research... Jul 2024Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its...
Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its clinical importance, the correlation between neuronal activity and the expression of voltage-gated sodium channel 1.7 (Nav1.7) in the trigeminal ganglion (TG) during pulpitis is less investigated. The aim of this study was to examine the relationship between experimentally induced pulpitis and Nav1.7 expression in the TG and to investigate the potential of selective Nav1.7 modulation to attenuate TG abnormal activity associated with pulpitis. Acute pulpitis was induced at the maxillary molar (M1) using allyl isothiocyanate (AITC). The mice were divided into three groups: control, pulpitis model, and pulpitis model treated with ProTx-II, a selective Nav1.7 channel inhibitor. After three days following the surgery, we conducted a recording and comparative analysis of the neural activity of the TG utilizing in vivo optical imaging. Then immunohistochemistry and Western blot were performed to assess changes in the expression levels of extracellular signal-regulated kinase (ERK), c-Fos, collapsin response mediator protein-2 (CRMP2), and Nav1.7 channels. The optical imaging result showed significant neurological excitation in pulpitis TGs. Nav1.7 expressions exhibited upregulation, accompanied by signaling molecular changes suggestive of inflammation and neuroplasticity. In addition, inhibition of Nav1.7 led to reduced neural activity and subsequent decreases in ERK, c-Fos, and CRMP2 levels. These findings suggest the potential for targeting overexpressed Nav1.7 channels to alleviate pain associated with pulpitis, providing practical pain management strategies.
Topics: Animals; NAV1.7 Voltage-Gated Sodium Channel; Mice; Male; Pulpitis; Trigeminal Ganglion; Neurons; Nerve Tissue Proteins; Proto-Oncogene Proteins c-fos; Voltage-Gated Sodium Channel Blockers; Disease Models, Animal; Intercellular Signaling Peptides and Proteins
PubMed: 38718567
DOI: 10.1016/j.bbrc.2024.150044 -
Neuroscience Letters May 2024Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4)...
BACKGROUND
Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4) modulates the activation of the NF-κB pathway to affect neuropathic pain in rats. Voltage-gated sodium channels (VGSCs) are known to play an important role in neuropathic pain electrical activity.
OBJECTIVE
To investigate whether TLR4 can regulate Nav1.3 through the TRAF6/NF-κB p65 pathway after infraorbital nerve chronic constriction injury (ION-CCI).
STUDY DESIGN
ION-CCI modeling was performed on SD (Sprague Dawley) rats. To verify the success of the modeling, we need to detect the mechanical pain threshold and ATF3. Then, detecting the expression of TLR4, TRAF6, NF-κB p65, p-p65, and Nav1.3 in rat TG. Subsequently, investigate the role of TLR4/TRAF6/NF-κB pathway in ION-CCI model by intrathecal injections of LPS-rs (TLR4 antagonist), C25-140 (TRAF6 inhibitor), and PDTC (NF-κB p65 inhibitor).
RESULTS
ION-CCI surgery decreased the mechanical pain threshold of rats and increased the expression of ATF3, TLR4, TRAF6, NF-κB p-p65 and Nav1.3, but there was no difference in NF-κB p65 expression. After inject antagonist or inhibitor of the TLR4/TRAF6/NF-κB pathway, the expression of Nav1.3 was decreased and mechanical pain threshold was increased.
CONCLUSION
In the rat model of ION-CCI, TLR4 in the rat trigeminal ganglion regulates Nav1.3 through the TRAF6/NF-κB p65 pathway, and TLR4 antagonist alleviates neuropathic pain in ION-CCI rats.
Topics: Animals; Toll-Like Receptor 4; Rats, Sprague-Dawley; TNF Receptor-Associated Factor 6; Male; NAV1.3 Voltage-Gated Sodium Channel; Signal Transduction; NF-kappa B; Trigeminal Neuralgia; Rats; Disease Models, Animal; Transcription Factor RelA; Activating Transcription Factor 3; Pain Threshold
PubMed: 38714229
DOI: 10.1016/j.neulet.2024.137806 -
Cureus Apr 2024Herpes zoster ophthalmicus (HZO) is a condition resulting from the reactivation of dormant varicella zoster virus within the sensory nerve ganglion in the ophthalmic...
Herpes zoster ophthalmicus (HZO) is a condition resulting from the reactivation of dormant varicella zoster virus within the sensory nerve ganglion in the ophthalmic branch of the trigeminal nerve. The tell-tale rash along one side of the nerve tract accompanied by pain, a burning sensation, and itching alerts health practitioners on the right path to diagnosis. Conversely, HZO can present with other rarer complications such as intraocular and extraocular manifestations. This case report deals with a seemingly healthy 45-year-old female who developed left abducens nerve palsy within one week of developing a vesicular rash on the same side. Curiously, those afflicted are usually of an advanced age or suffer from an immunocompromised state; this patient however suffered from no other comorbidities nor did she report having been in contact with anyone of a similar affliction. In this case, the classical treatment regime of antivirals and corticosteroids resulted in the complete resolution of the infection and the return of full ocular function. Being able to recognize and appreciate these typical and atypical signs and symptoms of HZO can aid in the further propagation of good outcomes and timely resolutions.
PubMed: 38707108
DOI: 10.7759/cureus.57506 -
Military Medical Research Apr 2024The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain...
BACKGROUND
The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood.
METHODS
Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund's adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice.
RESULTS
Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of β-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG.
CONCLUSIONS
The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.
Topics: Animals; Connexins; Mice; Nerve Tissue Proteins; Disease Models, Animal; Pain; Neurons; Inflammation; Mice, Knockout; Male
PubMed: 38685116
DOI: 10.1186/s40779-024-00525-8 -
Brain Sciences Mar 2024Migraine, recognized as a severe headache disorder, is widely prevalent, significantly impacting the quality of life for those affected. This article aims to provide a... (Review)
Review
Migraine, recognized as a severe headache disorder, is widely prevalent, significantly impacting the quality of life for those affected. This article aims to provide a comprehensive review of the application of animal model technologies in unraveling the pathomechanism of migraine and developing more effective therapies. It introduces a variety of animal experimental models used in migraine research, emphasizing their versatility and importance in simulating various aspects of the condition. It details the benefits arising from the utilization of these models, emphasizing their role in elucidating pain mechanisms, clarifying trigeminal activation, as well as replicating migraine symptoms and histological changes. In addition, the article consciously acknowledges the inherent limitations and challenges associated with the application of animal experimental models. Recognizing these constraints is a fundamental step toward fine-tuning and optimizing the models for a more accurate reflection of and translatability to the human environment. Overall, a detailed and comprehensive understanding of migraine animal models is crucial for navigating the complexity of the disease. These findings not only provide a deeper insight into the multifaceted nature of migraine but also serve as a foundation for developing effective therapeutic strategies that specifically address the unique challenges arising from migraine pathology.
PubMed: 38671969
DOI: 10.3390/brainsci14040317 -
Cells Apr 2024Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate...
Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.
Topics: Animals; Calcitonin Gene-Related Peptide; Dura Mater; Male; Rats; Subarachnoid Hemorrhage; Neurons; Rats, Sprague-Dawley; Trigeminal Ganglion; RNA, Messenger; Trigeminal Nerve
PubMed: 38667268
DOI: 10.3390/cells13080653 -
Cureus Mar 2024Epstein-Barr virus (EBV) can cause follicular conjunctivitis, keratitis, oculoglandular syndrome, meningitis, and encephalitis. We report a 54-year-old Hispanic male who...
Epstein-Barr virus (EBV) can cause follicular conjunctivitis, keratitis, oculoglandular syndrome, meningitis, and encephalitis. We report a 54-year-old Hispanic male who presented with right pupil-involved complete ophthalmoplegia, orbital and masticatory muscle inflammation, trigeminal enhancement, and new corneal infiltrate highly suggestive of EBV. Labwork was negative except for positive EBV polymerase chain reaction (PCR) in serum. Magnetic resonance imaging (MRI) of his brain and orbits with contrast showed enhancement of the right ganglion of the trigeminal nerve, oculomotor nerve, all extraocular muscles in the right orbit, and right masticatory and temporalis muscles and a right subacute lacunar infarct. The patient was diagnosed with encephalitis and orbital-face inflammation secondary to EBV infection. The patient improved with systemic steroids.
PubMed: 38659504
DOI: 10.7759/cureus.56888