scholarly journals AMPA receptor localization in trigeminal ganglion and its upregulation in migraine

2019 ◽  
Vol 10 (3) ◽  
pp. 2209-2212
Author(s):  
Sankaran PK ◽  
Gunapriya R ◽  
Yuvaraj MF ◽  
Siva T ◽  
Kumaresan M ◽  
...  

Migraine is characterized by headache due to imbalance between excitation and inhibition of neurons disabling normal day to day activities. The excitations of neurons are done by excitatory neurotransmitter glutamate which plays the key role in creating any pathology related to neurons. This study was done to identify GluR1 a subunit of AMPA glutamate receptor in the cells of trigeminal ganglion after inducing migraine and compare it with control rats. The GluR1 subunits were localized in the cytoplasm of neurons, and these subunits were up-regulated following a migraine. The GluR1 was also localized in satellite glial cells and nerve fibers, indicating these subunits expressed in neurons and migrate during nociceptive sensitization. This GluR1 expression in the cells of trigeminal ganglion may be crucial in nociceptive sensitization leading to migraine and other painful conditions like trigeminal neuralgia.

2020 ◽  
Vol 11 ◽  
pp. 412
Author(s):  
Salvador Somaza ◽  
Eglee M. Montilla

Background: There are many theories about the cause of trigeminal neuralgia (TN). None of them satisfactorily explains how demyelination alone through the ephaptic mechanism can contribute to the development of the TN crisis. The main characteristic of TN pain is its dynamic nature, which is difficult to explain based only on anatomical findings. With these antecedents, the exact mechanism by which radiosurgery produces pain relief in TN is unknown. Methods: It is based on the trigeminal ganglion (TG) cytoarchitecture and the pathophysiological findings observed after an injury to a trigeminal branch. TG seems to have a predominant role given its cellular structure. The neuronal component in sensory ganglia is generally surrounded by a single layer of satellite glial cells (SGC), which forms a sheath around each body cell. There is increasing evidence that SGCs play a key role in nociception. This depends on their ability to influence the neuronal excitability that occurs in conditions of neuropathic and inflammatory pain; contributing to both the generation and maintenance of pain. Results: We have already published the beneficial effects of radiosurgery on the TG for the treatment of idiopathic TN and secondary to vertebrobasilar ectasia. Now, we are investigating the functioning of the TG and how radiosurgery could act on the SGC, deactivating them, and contributing to the decrease or disappearance of the painful condition. Conclusion: We are postulating a theory on how radiosurgery in TG produces changes in the SGC, with implications in the pathological mechanisms initiated by the alteration caused in the neuron after a nerve injury.


2019 ◽  
Vol 10 ◽  
pp. 89
Author(s):  
Salvador Somaza ◽  
Eglee M. Montilla ◽  
Maria C. Mora

Background: In the present study, we evaluate the results of gamma knife surgery (GKS) for the treatment of trigeminal neuralgia (TN) using the trigeminal ganglion (TG’) and the adjacent fibers of trigeminal nerve as a target. Methods: From February 2013 to July 2017, we treated 30 cases of TN with GKS. In this group, all patients had an idiopathic typical TN. The radiosurgical target was conformed through two isocenters, 8 and 4 mm at the cavum de Meckel. The maximum dose was 86 Gy using the isodose line of 50%. The median age of the patients was 58.5 (range 28–94) years old, and the median time from diagnosis to GKS was 94 months (range 13–480 months). The median follow-up was 28.5 (range 12–49) months. Clinical outcomes were analyzed. Univariate and multivariate analyses were performed to evaluate factors that correlated with a favorable, pain-free outcome. Results: The mean time to relief of pain was 7 (range 1–40) days. The percentage of patients with significant pain relief was 93.3%. Relapse in pain was noted in four patients at 3, 16, 19, and 36 months. Nine patients were treated in acute status. Fourteen patients had intense pain between 1 and 7 days before the procedure. Among those with the recurrence of their symptoms, one patient had a microvascular decompression. Multivariate regression adjusted for age and sex suggests that, by 40 months, 70% of the patients treated with radiosurgery will remain pain free. At the last follow-up, GKS resulted in pain relief in 86.6% of patients. Our analysis suggests that, using this technique, we can expect that approximately 70% of patients with TN will have some degree of pain improvement at 3 years’ post radiosurgery. Conclusions: GKS on TG appears to be a reasonable treatment option with short latency period, minor collateral effects, and high percentage of pain control. The mechanism of action of radiosurgery could be related to the inactivation of the satellite glial cells in the TG.


Author(s):  
B.F. Hoeflinger ◽  
W.T. Gunning ◽  
J.A. Brown ◽  
A. Eckhardt ◽  
M. McDaniel ◽  
...  

Trigeminal neuralgia (TN) is a disorder characterized by paroxysmal, lancing facial pain confined to the distribution of trigeminal nerve fibers. A procedure to relieve this sensation, Percutaneous Trigeminal Ganglion Compression(PTGC), was introduced in 1983 and has been shown in clinical studies to be an effective treatment for TN. The effect of PTGC on the trigeminal system has not been adequately studied. In a previous study. New Zealand White rabbits were utilized in an attempt to evaluate the consequences of PTGC at the light microscopic level. This investigation revealed a differential demyelination and fragmentation of axons in the trigeminal(V) sensory root while trigeminal ganglion neurons were found to be preserved. Immunocytochemical stains of the spinal trigeminal tract showed no specific loss of fine caliber Ad and C-fibers. Degeneration of axon terminals was found in the deeper layers of the spinal trigeminal nucleus, the region corresponding to the termination of large myelinated axons suggesting a differential loss of these specific fibers.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 636
Author(s):  
Lindsay M. Achzet ◽  
Fanny Astruc-Diaz ◽  
Phillip H. Beske ◽  
Nicholas R. Natale ◽  
Travis T. Denton ◽  
...  

Strokes remain one of the leading causes of disability within the United States. Despite an enormous amount of research effort within the scientific community, very few therapeutics are available for stroke patients. Cytotoxic accumulation of intracellular calcium is a well-studied phenomenon that occurs following ischemic stroke. This intracellular calcium overload results from excessive release of the excitatory neurotransmitter glutamate, a process known as excitotoxicity. Calcium-permeable AMPA receptors (AMPARs), lacking the GluA2 subunit, contribute to calcium cytotoxicity and subsequent neuronal death. The internalization and subsequent degradation of GluA2 AMPAR subunits following oxygen–glucose deprivation/reperfusion (OGD/R) is, at least in part, mediated by protein-interacting with C kinase-1 (PICK1). The purpose of the present study is to evaluate whether treatment with a PICK1 inhibitor, FSC231, prevents the OGD/R-induced degradation of the GluA2 AMPAR subunit. Utilizing an acute rodent hippocampal slice model system, we determined that pretreatment with FSC231 prevented the OGD/R-induced association of PICK1–GluA2. FSC231 treatment during OGD/R rescues total GluA2 AMPAR subunit protein levels. This suggests that the interaction between GluA2 and PICK1 serves as an important step in the ischemic/reperfusion-induced reduction in total GluA2 levels.


2020 ◽  
Vol 32 (6) ◽  
pp. 790-798 ◽  
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Rachel Wolfe ◽  
Ajay Niranjan ◽  
John C. Flickinger ◽  
...  

OBJECTIVEStereotactic radiosurgery (SRS) has been used to treat trigeminal neuralgia by targeting the cisternal segment of the trigeminal nerve, which in turn triggers changes in the gasserian ganglion. In the lumbar spine, the dorsal root ganglion (DRG) is responsible for transmitting pain sensitivity and is involved in the pathogenesis of peripheral neuropathic pain. Therefore, radiosurgery to the DRG might improve chronic peripheral pain. This study evaluated the clinical and histological effects of high-dose radiosurgery to the DRG in a rodent model.METHODSEight Sprague-Dawley rats received either 40- or 80-Gy SRS to the fifth and sixth lumbar DRGs using the Leksell Gamma Knife Icon. Animals were euthanized 3 months after treatment, and the lumbar spine was dissected and taken for analysis. Simple histology was used to assess collagen deposition and inflammatory response. GFAP, Neu-N, substance P, and internexin were used as a measure of peripheral glial activation, neurogenesis, pain-specific neurotransmission, and neurotransmission in general, respectively. The integrity of the spinothalamic tract was assessed by means of the von Frey test.RESULTSThe animals did not exhibit any signs of motor or sensory deficits during the experimentation period. Edema, fibrosis, and vascular sclerotic changes were present on the treated, but not the control, side. SRS reduced the expression of GFAP without affecting the expression of Neu-N, substance P, or internexin. The von Frey sensory perception elicited equivalent results for the control side and both radiosurgical doses.CONCLUSIONSSRS did not alter sensory or motor function but reduced the activation of satellite glial cells, a pathway for DRG-mediated pain perpetuation. Radiosurgery provoked changes equivalent to the effects of focal radiation on the trigeminal ganglion after SRS for trigeminal neuralgia, suggesting that radiosurgery could be successful in relieving radiculopathic pain.


2004 ◽  
Vol 101 (5) ◽  
pp. 872-873 ◽  
Author(s):  
Kim J. Burchiel ◽  
Thomas K. Baumann

✓ The origin of trigeminal neuralgia (TN) appears to be vascular compression of the trigeminal nerve at the root entry zone; however, the physiological mechanism of this disorder remains uncertain. The authors obtained intraoperative microneurographic recordings from trigeminal ganglion neurons in a patient with TN immediately before percutaneous radiofrequency-induced gangliolysis. Their findings are consistent with the idea that the pain of TN is generated, at least in part, by an abnormal discharge within the peripheral nervous system.


2007 ◽  
Vol 98 (3) ◽  
pp. 1083-1101 ◽  
Author(s):  
Joseph C. Holt ◽  
Shilpa Chatlani ◽  
Anna Lysakowski ◽  
Jay M. Goldberg

Intracellular recordings were made from nerve fibers in the posterior ampullary nerve near the neuroepithelium. Calyx-bearing afferents were identified by their distinctive efferent-mediated responses. Such fibers receive inputs from both type I and type II hair cells. Type II inputs are made by synapses on the outer face of the calyx ending and on the boutons of dimorphic fibers. Quantal activity, consisting of brief mEPSPs, is reduced by lowering the external concentration of Ca2+ and blocked by the AMPA-receptor antagonist CNQX. Poisson statistics govern the timing of mEPSPs, which occur at high rates (250–2,500/s) in the absence of mechanical stimulation. Excitation produced by canal-duct indentation can increase mEPSP rates to nearly 5,000/s. As the rate increases, mEPSPs can change from a monophasic depolarization to a biphasic depolarizing–hyperpolarizing sequence, both of whose components are blocked by CNQX. Blockers of voltage-gated currents affect mEPSP size, which is decreased by TTX and is increased by linopirdine. mEPSP size decreases severalfold after impalement. The size decrease, although it may be triggered by the depolarization occurring during impalement, persists even at hyperpolarized membrane potentials. Nonquantal transmission is indicated by shot-noise calculations and by the presence of voltage modulations after quantal activity is abolished pharmacologically. An ultrastructural study shows that inner-face inputs from type I hair cells outnumber outer-face inputs from type II hair cells by an almost 6:1 ratio.


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