Kv4.3 Channel Dysfunction Contributes to Trigeminal Neuropathic Pain Manifested with Orofacial Cold Hypersensitivity in Rats

Trigeminal neuropathic pain is the most debilitating pain disorder but current treatments including opiates are not effective. A common symptom of trigeminal neuropathic pain is cold allodynia/hyperalgesia or cold hypersensitivity in orofacial area, a region where exposure to cooling temperatures are inevitable in daily life. Mechanisms underlying trigeminal neuropathic pain manifested with cold hypersensitivity are not fully understood. In this study, we investigated trigeminal neuropathic pain in male rats following infraorbital nerve chronic constrictive injury (ION-CCI). Assessed by the orofacial operant behavioral test, ION-CCI animals displayed orofacial cold hypersensitivity. The cold hypersensitivity was associated with the hyperexcitability of small-sized trigeminal ganglion (TG) neurons that innervated orofacial regions. Furthermore, ION-CCI resulted in a reduction of A-type voltage-gated K⁺ currents (IA currents) in these TG neurons. We further showed that these small-sized TG neurons expressed Kv4.3 voltage-gated K⁺ channels, and Kv4.3 expression in these cells was significantly downregulated following ION-CCI. Pharmacological inhibition of Kv4.3 channels with phrixotoxin-2 inhibited IA-currents in these TG neurons and induced orofacial cold hypersensitivity. On the other hand, pharmacological potentiation of Kv4.3 channels amplified IA currents in these TG neurons and alleviated orofacial cold hypersensitivity in ION-CCI rats. Collectively, Kv4.3 downregulation in nociceptive trigeminal afferent fibers may contribute to peripheral cold hypersensitivity following trigeminal nerve injury, and Kv4.3 activators may be clinically useful to alleviate trigeminal neuropathic pain.SIGNIFICANCE STATEMENT Trigeminal neuropathic pain, the most debilitating pain disorder, is often triggered and exacerbated by cooling temperatures. Here, we created infraorbital nerve chronic constrictive injury (ION-CCI) in rats, an animal model of trigeminal neuropathic pain to show that dysfunction of Kv4.3 voltage-gated K⁺ channels in nociceptive-like trigeminal ganglion (TG) neurons underlies the trigeminal neuropathic pain manifested with cold hypersensitivity in orofacial regions. Furthermore, we demonstrate that pharmacological potentiation of Kv4.3 channels can alleviate orofacial cold hypersensitivity in ION-CCI rats. Our results may have clinical implications in trigeminal neuropathic pain in human patients, and Kv4.3 channels may be an effective therapeutic target for this devastating pain disorder.     

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

First emerging objective experimental evidence of hearing impairment following subarachnoid haemorrhage; Felix culpa,phonophobia, and elucidation of the role of trigeminal ganglion

Objective: The exact mechanism of phonophobia induced by subarachnoid hemorrhage (SAH) has not been understood well. This subject was investigated.

Material and methods: This study was conducted on 25 rabbits. They divided into three groups: Five as control, five as SHAM, 20 as SAH group. All animals objected to 85?dB impulse noise by daily periods, and their phonophobic score values were examined by daily periods for 20 days. Their brains, trigeminal ganglia were extracted bilaterally. The normal and degenerated neuron densities of trigeminal ganglia were examined by stereological methods and compared with phonophobia scores.

Results: Phonophobic score was 19-17, mean live neuron density (LND) of the trigeminal ganglia was 16.321?±?2.430/mm³, and degenerated neuron density (DND) was 1.15?±?0.120/mm³ in animals of control groups (n?=?5). The phonophobic score was 17-14, LND: 14.345?±?1.913/mm³, DND of the trigeminal ganglia was 1.150?±?0.110/mm³ in SHAM group (n?=?5). The phonophobic score was 14-8, LND: 12.987?±?1.966/mm³, mean DND of the trigeminal ganglia was 2.520?±?510/mm³ in animals with high phonophobia scores (n?=?6). The phonophobic score was 7-4, LND: 9.122?±?1.006, mean DND of the trigeminal ganglia was 5.820?±?1.610/mm³, in animals with fever phonophobia scores (n?=?9).

Conclusion: An inverse relationship between DND trigeminal ganglion (TGG) and phonopobic score was found. The paralysis of tensor tympani muscle owing to trigeminal ganglia ischemia may be responsible for phonophobic clinical state in animals with SAH. In addition, there seems to be an important concern for the verbal component of GCS in SAH. These two important findings have not been published previously.     

Analysis of morphological measurements of the trigeminal nerve in the linac stereotactic radiosurgery simulation targeting the root entry zone in trigeminal neuralgia

PurposeTo describe the anatomical measurements of the trigeminal nerve in patients with trigeminal neuralgia (TN) during Linac (linear accelerator)-based stereotactic radiosurgery (SRS) simulation, targeting the root entry zone (REZ), with a 30% isodose line tangential to the pons, using 4-mm and 6-mm collimators.MethodsIn this retrospective study, 53 TN patients, who underwent Fiesta sequence scanning prior to any treatment modality, were assessed. Bilateral measurements were obtained from the cisternal segment of the trigeminal nerve, the trigeminal-pontine angle, and the lateral width of the pontine cistern on the Fiesta MRI sequence. Linac-based SRS simulations were estimated with a radiation dosage of 90 Gy to 30% isodose line tangential to the pons, with both 4- and 6-mm collimators. Distances from the calculated targets to the pons and the Gasserian ganglion were measured for later analysis. The statistical analysis was performed comparing the affected side against the unaffected side.ResultsRight trigeminal nerve was affected in 36 patients (67.9%), and left one in 17 (32.1%) patients. The mean length of the trigeminal nerve was 9.8 mm (range: 4.6–16.8 mm) on the affected side, and 10.5 mm (range: 5.6–18.4 mm) on the unaffected side (p = .02). The mean trigeminal-pontine angle was 12.5° (range: 5.4° to 19.5°) on the affected side, and 10.2° (range: 5.0° to 30.5°) on the unaffected side (p = .01). In the simulations, the distances from the estimated targets to the pons and the Gasserian ganglion were not statistically different between sides. The variation of target-pons and target-ganglion distances was statistically significant on the affected side with the change of collimators (p < .001).ConclusionsIn this anatomical study, significant differences were identified in the length of the affected trigeminal nerve and trigeminal-pontine angle compared to the unaffected side in TN patients in Fiesta sequences prior to surgery or radiosurgery. Significant variation of the target location was found on the REZ between the 4- and 6-collimators during the Linac-based SRS simulations with the estimated radiation dosage of 90 Gy and 30% isodose line tangential to the pons.     

Expression and localization of the Nav1.9 sodium channel in enteric neurons and in trigeminal sensory endings: implication for intestinal reflex function and orofacial pain

The Nav1.9 sodium channel is expressed in nociceptive DRG neurons where it contributes to spontaneous pain behavior after peripheral inflammation. Here, we used a newly developed antibody to investigate the distribution of Nav1.9 in rat and mouse trigeminal ganglion (TG) nerve endings and in enteric nervous system (ENS). In TGs, Nav1.9 was expressed in the soma of small- and medium-sized, peripherin-positive neurons. Nav1.9 was present along trigeminal afferent fibers and at terminals in lip skin and dental pulp. In the ENS, Nav1.9 was detected within the soma and proximal axons of sensory, Dogiel type II, myenteric and submucosal neurons. Immunological data were correlated with the detection of persistent TTX-resistant Na(+) currents sharing similar properties in DRG, TG and myenteric neurons. Collectively, our data support a potential role of Nav1.9 in the transmission of trigeminal pain and the regulation of intestinal reflexes. Nav1.9 might therefore constitute a molecular target for therapeutic treatments of orofacial pain and gastrointestinal syndromes.     

Proteomic Analysis of the Hippocampus in Mouse Models of Trigeminal Neuralgia and Inescapable Shock-Induced Depression

To investigate the behavioral and biomolecular similarity between neuralgia and depression, a trigeminal neuralgia (TN) mouse model was established by constriction of the infraorbital nerve (CION) to mimic clinical trigeminal neuropathic pain. A mouse learned helplessness (LH) model was developed to investigate inescapable foot-shock-induced psychiatric disorders like depression in humans. Mass spectrometry was used to assess changes in the biomolecules and signaling pathways in the hippocampus from TN or LH mice. TN mice developed not only significant mechanical allodynia but also depressive-like behaviors (mainly behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis demonstrated common and distinctive protein changes in the hippocampus between groups. Many protein function families (such as cell-to-cell signaling and interaction, and cell assembly and organization,) and signaling pathways (e.g., the Huntington’s disease pathway) were involved in chronic neuralgia and depression. Together, these results demonstrated that the LH and TN models both develop depressive-like behaviors, and revealed the involvement of many psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and LH.     

Migraine in pregnancy and lactation

Whether arterial or venous compression or arachnoid adhesions are primarily responsible for compression of the trigeminal nerve in patients with trigeminal neuralgia is unclear. The aim of this study was to determine the causes of trigeminal nerve compression in patients with trigeminal neuralgia. The surgical findings in patients with trigeminal neuralgia who were treated by micro vascular decompression were compared to those in patients with hemifacial spasm without any signs or symptoms of trigeminal neuralgia who were treated with microvascular decompression. The study included 99 patients with trigeminal neuralgia (median age, 57 years) and 101 patients with hemifacial spasm (median age, 47 years). There were significant differences between the groups in the relationship of artery to nerve (p < 0.001) and the presence of arachnoid adhesions (p < 0.001) but no significant difference in relationship of vein to nerve. After adjustment for age, gender, and other factors, patients with vein compression of nerve or with artery compression of nerve were more likely to have trigeminal neuralgia (OR = 5.21 and 42.54, p = 0.026 and p < 0.001, respectively). Patients with arachnoid adhesions were less likely to have trigeminal neuralgia (OR = 0.15, p = 0.038). Arterial compression of the trigeminal nerve is the primary cause of trigeminal neuralgia and therefore, decompression of veins need not be a priority when performing microvascular dissection in patients with trigeminal neuralgia.     

Anatomical consequences of neonatal infraorbital nerve transection upon the trigeminal ganglion and vibrissa follicle nerves in the adult rat

A large body of experimental literature has demonstrated that neonatal infraorbital nerve damage in rodents produces anatomical and/or functional alterations of the normal whisker representation in central trigeminal structures. Less is known about the organization of primary afferent components of the trigeminal system following this manipulation. Such information provides an important basis for interpreting the central changes observed following damage of infraorbital nerve fibers at birth. We have therefore examined the composition and order of peripheral innervation in the pathway from the trigeminal ganglion to the vibrissa follicles in adult rats subjected to unilateral neonatal infraorbital nerve transection. Electron microscopy was used to determine the number and diameter of myelinated and unmyelinated fibers in vibrissa follicle nerves of these animals. Wheat germ agglutinin-horseradish peroxidase and fluorescent retrograde tracers were employed to examine the number and diameter, as well as the topographic organization and branching, of ganglion cells innervating the vibrissae in these rats. The data presented below indicate that neonatal infraorbital nerve transection has the following consequences within the adult trigeminal nerve and ganglion: 1) an alteration of the gross morphology of vibrissal nerves, 2) a significant reduction in the average number (85.4%) and diameter (32.6%) of myelinated, but not unmyelinated, follicle nerve axons, 3) a significant decrease in the average number (36.8%) of trigeminal ganglion cells innervating vibrissa follicles, 4) no significant change in the distribution of ganglion cell diameters, 5) an increase in peripheral branching (1.8-fold) of these ganglion cell axons, and 6) an alteration of somatotopic order within the trigeminal ganglion. Taken together, these data indicate that neonatal infraorbital nerve transection produces a profound reorganization of the primary afferent component of the trigeminal neuraxis.     

Effect of pulmonary vein isolation on the relationship between left atrial reverse remodeling and sympathetic nerve activity in patients with atrial fibrillation

Purpose

Catheter ablation (CA) to isolate the pulmonary vein, which is an established treatment for atrial fibrillation (AF), is associated with left atrium reverse remodeling (LARR). The intrinsic cardiac autonomic nervous system includes the ganglion plexi adjacent to the pulmonary vein in the left atrium (LA). However, little is known about the effect of CA on the relationship between LARR and sympathetic nerve activity in patients with AF.

Methods

This study enrolled 22 AF patients with a normal left ventricular ejection fraction (LVEF) aged 64.6?±?12.9 years who were scheduled for CA. Sympathetic nerve activity was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) before and 12 weeks after CA. Blood pressure, heart rate (HR), HR variability, and echocardiography were also measured.

Results

The heart rate increased significantly after CA (63?±?10.9 vs. 70.6?±?7.7 beats/min, p?<?0.01), but blood pressure did not change. A high frequency (HF) and low frequency (LF) of HR variability decreased significantly after ablation, but no significant change in LF/HF was observed. CA significantly decreased MSNA (38.9?±?9.9 vs. 28?±?9.1 bursts/min, p?<?0.01). Moreover, regression analysis revealed a positive correlation between the percentage change in MSNA and the LA volume index (r?=?0.442, p?<?0.05).

Conclusions

Our results show that CA for AF reduced MSNA and the decrease was associated with the LA volume index in AF patients with a normal LVEF. These findings suggest that LARR induced by CA for AF decrease sympathetic nerve activity.

     

Assessment of the Outcomes of Cerebral Blood Flow Measurements After Electrical Stimulation of Upper Right Incisor Tooth in Rabbits

The cerebral vessels are innervated by sympathetic, parasympathetic, and sensory nerves. A sensory innervation of the cerebral vessels originating in the trigeminal ganglion has been described in a number of species by several investigations. It has been shown that the electrical stimulation of the trigeminal ganglion causes an increase of cerebral cortical blood flow (CCoBF). The aim of the present study was to determine the effects of dental electrical stimulation the CCoBF in rabbits. A stimulating electrode was located in the upper right incisor tooth of rabbits and trigeminal ganglion was stimulated orthodromically via the infraorbital nerve. Variations in the cortical CCoBF were evaluated by laser-Doppler flowmetry. In experiment group, CCoBF increased together with the beginning of electrical stimulation (5 V, 0.5-ms impulse duration, square-shaped, 10-Hz frequency). The right and left hemisphere CCoBF values of stimulation period at 15s, 30s, 45s, 60s, 75s, and 90s were significantly higher than those of baseline and 105 and 120s (p < 0.05). The maximum increase in right and left CCoBF was 15.6% and 15.1% respectively. In post-stimulation period, the right CCoBF decreased gradually and returned to the baseline values at 120 s. In experiment groups, the CCoBF values of right hemisphere were comparable that of left hemisphereL (p > 0.05). This study demonstrated that the electrical stimulation of the trigeminal nerve's infraorbital branch via dental pulp increases the cortical right and left CCoBF under physiological conditions.     

采用经皮热凝神经术辅助经皮热凝三叉神经节根治疗三叉神经痛

目的总结采用经皮热凝上颚神经以辅助标准的经皮热凝三叉神经节根治疗三叉神经痛的经验.方法第一组：13例有三叉神经第二支与第三支疼痛的典型三叉神经痛病人,接受标准神经节根热凝术,同时辅助以经皮热凝眶下上颚神经.第二组：12例过去接受热凝神经节根治疗的病人,复发疼痛于V2,但V3未复发.采用经皮热凝眶下神经做为权宜的缓解疗法,而不必再施行神经节根热凝术.结果第一组病人经合并两法治疗后,获得满意的疗效,在V2区获得无痛,而V3区仅轻度麻木,且几乎没有咀嚼功能障碍,疗效维持3年,未见复发.第二组病人,仅施行简单的神经热凝术,不需重做神经节根的热凝术,即可获得满意的缓解复发疼痛,疗效可维持1年.结论针对某些病例,热凝三叉神经节根辅助以经皮热凝上颚神经,比起只做三叉神经节根热凝术的结果优越,可避免脸部过度麻木与咀嚼功能的障碍,不会产生痛性麻木.对于仅限于V2复发疼痛的病人,采用权宜简单的经皮热凝眶下神经,可有效解除其复发,而不需重做神经节根的热凝治疗,避免恶化其副作用.     

TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca²⁺ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.     

A comparison of health-related quality of life in autonomic disorders: postural tachycardia syndrome versus vasovagal syncope

Purpose

Postural tachycardia syndrome (POTS) and vasovagal syncope (VVS) are two disorders of orthostatic intolerance which are often misdiagnosed as the other. In each case, patients experience a reduced health-related quality of life (HRQoL) compared to healthy populations. This study was conducted to test the hypothesis that HRQoL is worse in POTS.

Methods

POTS patients were recruited from the Dysautonomia International Annual Patient and Caregiver Conference. VVS patient data came from those enrolled in the Second Prevention of Syncope Trial. Participants aged?≥?18 years (177 POTS and 72 VVS) completed the RAND 36-Item Health Survey, a generic and coherent health-related quality of life survey.

Results

POTS patients reported reduced HRQoL compared to VVS patients in physical functioning (42.5?±?1.7 vs. 76.5?±?2.9, p?<?0.001), role limitations due to physical health (11.4?±?1.9 vs. 33.0?±?5.0, p?<?0.001), energy and fatigue (27.2?±?1.3 vs. 50.7?±?2.6, p?<?0.001), social functioning (45.2?±?1.8 vs. 71.2?±?2.9, p?<?0.001), pain (48.8?±?1.9 vs. 67.7?±?2.9, p?<?0.001), and general health (31.2?±?1.5 vs. 60.5?±?2.6, p?<?0.001) domains. Scores did not differ significantly in the role limitations due to emotional health (p?=?0.052) and emotional well-being (p?=?0.271) domains. Physical and general health composite scores were lower in the POTS population, while mental health composite scores were not different.

Conclusion

Differences in HRQoL exist between these patient populations. POTS patients report lower scores in physical and general health domains than VVS patients, but emotional health domains do not differ significantly. Targeting physical functioning in these patients may help improve quality of life.

     

Cardiovascular adjustments to cold pressor test in postmenopausal women and the impact of α1-adrenergic blockade

Purpose

We investigate the impact of menopause on cardiovascular adjustments to the cold pressor test (CPT) and the role of the α1-adrenergic receptor.

Methods

Ten young women (YW) and nine postmenopausal women (MW) underwent 1 min of CPT in control and α1-blockade conditions (0.03 mg?kg^?1 of oral prazosin).

Results

CPT increased heart rate (HR) (YW: ?20?±?3 bpm; MW: ?13?±?2 bpm) and stroke volume (SV; YW: ?15?±?8 ml; MW: ?9?±?6 ml; p?=?0.01 for time) and evoked a greater increase in cardiac output (CO) in YW (YW: ?2.1?±?0.2 l?m^?1; MW: ?1.3?±?0.5 l?m^?1; p?=?0.01). α1-Blockade increased baseline HR and did not change HR, SV, and CO responses to CPT. MW presented an exaggerated systolic blood pressure (BP) response (YW: ?38?±?9 mmHg; MW: ?56?±?24 mmHg; p?=?0.03). The α1-blockade did not change baseline BP while blunting its response. Total vascular resistance (TVR) was similar between groups at baseline and increased during CPT only in MW (YW: ?2.3?±?1.4 mmHg?L^?1?min; MW:?6.8?±?5.9 mmHg?L^?1?min). Under α1-blockade, the TVR increase during CPT was attenuated in MW and abolished in YW (YW: ?0.3?±?1.2 mmHg?L^?1?min and MW: ?3.0?±?2.0 mmHg?L^?1?min). CPT did not change femoral vascular conductance (FVC) in either group before the blockade (YW: ??0.3?±?4.0 ml?min^?1?mmHg^?1; MW: ??0.2?±?0.8 ml?min^?1?mmHg^?1); however, FVC tended to increase in young women (YW: ?1.3?±?1.0 ml?min^?1?mmHg^?1; MW: ?0.1?±?1.5 ml?min^?1?mmHg^?1; p?=?0.06) after the α1-blockade.

Conclusion

In postmenopausal women, the cardiac ability to adjust to CPT is blunted and α1-adrenergic receptor stimulation is important for the increase in stroke volume. In addition, the peripheral effect of α1-adrenergic receptor stimulation seems to be increased in postmenopausal women.

     

Neuralgia del trigémino clásica familiar

Introduction

The classic form of trigeminal neuralgia is usually sporadic (no familial clustering). However, around 2% of all cases of trigeminal neuralgia may be familial. Describing this entity may be useful for diagnosing this process and may also be key to determining the underlying causes of sporadic classical trigeminal neuralgia. We report on cases in a series of 5 families with at least 2 members with classic trigeminal neuralgia, amounting to a total of 11 cases.

AbstractsInternational conference on conservative management of spinal deformities Barcelona 23–24 January 2004

Objective: To document the serial changes in bone mineral density (BMD) following paediatric spinal cord injury (SCI).

Design: Retrospective case series.

Setting: Paediatric tertiary care hospital.

Patients: Eighteen children (nine males) followed in an outpatient spinal cord injury service.

Interventions: Not applicable.

Main outcome measure: Serial bone mineral density (BMD) measurements using dual energy X-ray absorptiometry (DXA).

Results: Mean follow-up was 5.0?±?3.6 years (range 0.4–12.4 years). Three children sustained minimal trauma fractures, all femoral. For the cohort, BMD Z-scores were significantly less than zero in the legs (?2.7?±?2.0, p?p?p?=?0.02) and lumbar spine (?0.8?±?1.6, p?=?0.04), but not in the arms (?0.2?±?1.0, p?=?0.5). Lean tissue mass (LTM) Z-scores were reduced in the legs (?1.9?±?1.3, p?Z-scores in the 12 months following SCI, followed by an age appropriate increase thereafter.

Conclusions: Lower extremity osteopenia and sarcopenia develop rapidly in the first 12 months following the SCI. The reduced bone strength increases the risk of low trauma fracture.     

Eyes are mirror of the brain: comparison of multiple sclerosis patients and healthy controls using OCT

Abstract

Objective: To evaluate the thickness of choroid and retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis using enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods: In this cross-sectional study, both eyes of 52?MS patients [n?=?104 eyes; 62 eyes of MS patients without optic neuritis (MS-NON) and 42 eyes of MS patients with optic neuritis (MS-ON)] and only one eye of 36 healthy control subjects (n?=?36 eyes) were evaluated. Complete ophthalmologic examination and EDI-OCT scanning were completed for all participants. Choroidal thickness measurements were executed at three different points.

Results: Choroidal thickness measurements were similar between MS patients and healthy control subjects. However, the mean subfoveal choroidal thickness was increased significantly in MS-ON group (399.13?±?82.91?μm) compared to MS-NON group (342.71?±?82.46?μm; p?=?0.004). Mean RNFL thickness was significantly reduced in MS patients (90.42?±?13.31?μm) compared to healthy controls (101.18?±?10.75?μm; p?<?0.001). Moreover, temporal RNFL thickness was significantly thinner in MS-ON group (54?±?14.50?μm) than MS-NON group (62.15?±?15.88?μm; p?=?0.01). In MS patients, temporal RNFL thickness was correlated with both Expanded Disability Status Score (r?=?0.383; p?<?0.001) and longer disease duration (r=–0.202; p?=?0.04).

Conclusion: The results of the present study suggest that RNFL thickness can be used as an important parameter while following up with MS patients. However, more studies using EDI-OCT are required with larger MS patient groups and automated method.     

Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat

Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of α-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.