Arterial supply of the trigeminal ganglion, a micromorphological study.

BACKGROUND: In this study, we explored the specific microanatomical properties of the trigeminal ganglion (TG) blood supply and its close neurovascular relationships with the surrounding vessels. Possible clinical implications have been discussed. MATERIALS AND METHODS: The internal carotid and maxillary arteries of 25 adult and 4 foetal heads were injected with a 10% mixture of India ink and gelatin, and their TGs subsequently underwent microdissection, observation and morphometry under a stereoscopic microscope. RESULTS: The number of trigeminal arteries varied between 3 and 5 (mean 3.34), originating from 2 or 3 of the following sources: the inferolateral trunk (ILT) (100%), the meningohypophyseal trunk (MHT) (100%), and from the middle meningeal artery (MMA) (92%). In total, the mean diameter of the trigeminal branches was 0.222 mm. The trigeminal branch of the ILT supplied medial and middle parts of the TG, the branch of the MHT supplied the medial part of the TG, and the branch of the MMA supplied the lateral part of the TG. Additional arteries for the TG emerged from the dural vascular plexus and the vascular network of the plexal segment of the trigeminal nerve. Uniform and specific intraganglionicdense capillary network was observed for each sensory trigeminal neuron. CONCLUSIONS: The reported features of the TG vasculature could be implied in a safer setting for surgical approach to the skull base, in relation to the surrounding structures. The morphometric data on TG vasculature provide anatomical basis for better understanding the complex TG blood supply from the internal and external carotid arteries.

Persistent Trigeminal Artery: Neuroanatomic and Clinical Relevance.

INTRODUCTION: Persistent trigeminal artery (PTA) is the most common remnant of primitive circulation communicating the developing carotid and vertebrobasilar junction. Although discovered incidentally, an altered hemodynamic may lead to an increased association of aneurysms, vascular malformations, and stroke. Neurosurgeons should be aware of the presence and significance of PTA when interpreting imaging and planning interventions. METHODS: We retrospectively reviewed all magnetic resonance angiography and cerebral digital subtraction angiography performed between 2012 and 2017 for the presence of PTA. The radiologic and anatomic details were noted and analyzed along with the clinical profiles. We categorized the radiologic findings with respect to the available classification systems. A review of the available literature was done comparing our results. RESULTS: We found 33 cases of incidentally detected PTA. The average age of the patients was 45.42 years. The lateral surface of the proximal cavernous internal carotid artery was the most common origin (n = 23). Only 3 cases had a medial/transsellar course. Most cases were Saltzman/Weon type I (19/33). Intracranial aneurysms were associated with 6 patients (18.18%). Trigeminal neuralgia (TN) was a presenting feature in 5 patients. None had a direct neurovascular conflict at the root entry zone. CONCLUSIONS: Our study is one of the largest to describe the incidence of PTA. We emphasized the importance of PTA to the neurosurgeons; increased association of aneurysms, as a route for intervention in occlusive disease of the posterior fossa; risk of injury and bleeding during transsphenoidal surgery; and the association with TN. However, we found that only PTA variants are likely to be associated with TN because of their cisternal course causing NV conflict.

Gender aspects of CGRP in migraine.

BACKGROUND: Migraine is two to three times more prevalent in women than in men, but the mechanisms involved in this gender disparity are still poorly understood. In this respect, calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology and, more recently, the functional interactions between ovarian steroid hormones, CGRP and the trigeminovascular system have been recognized and studied in more detail. AIMS: To provide an overview of CGRP studies that have addressed gender differences utilizing animal and human migraine preclinical research models to highlight how the female trigeminovascular system responds differently in the presence of varying ovarian steroid hormones. CONCLUSIONS: Gender differences are evident in migraine. Several studies indicate that fluctuations of ovarian steroid hormone (mainly estrogen) levels modulate CGRP in the trigeminovascular system during different reproductive milestones. Such interactions need to be considered when conducting future animal and human experiments, since these differences may contribute to the development of gender-specific therapies.

Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation.

OBJECTIVE: Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. METHODS: This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. RESULTS: Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. CONCLUSIONS: Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

Migraine and neuropeptides.

Migraine is a common disabling neurovascular primary headache disorder. The pathomechanism is not clear, but extensive preclinical and clinical studies are ongoing. The structural basis of the leading hypothesis is the trigeminovascular system, which includes the trigeminal ganglion, the meningeal vasculature, and the distinct nuclei of the brainstem, the thalamus and the somatosensory cortex. This review covers the effects of sensory (calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide and substance P), sympathetic (neuropeptide Y) and parasympathetic (vasoactive intestinal peptide) migraine-related neuropeptides and the functions of somatostatin, nociceptin and the orexins in the trigeminovascular system. These neuropeptides may take part in neurogenic inflammation (plasma protein extravasation and vasodilatation) of the intracranial vasculature and peripheral and central sensitization of the trigeminal system. The results of human clinical studies are discussed with regard to the alterations in these neuropeptides in the plasma, saliva and cerebrospinal fluid during or between migraine attacks, and the therapeutic possibilities involving migraine-related neuropeptides in the acute and prophylactic treatment of migraine headache are surveyed.

Sensitization of the trigeminovascular system following environmental irritant exposure.

BACKGROUND: Air pollution is linked to increased emergency room visits for headache, and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that nasal administration of environmental irritants acutely increases meningeal blood flow via a TRPA1-dependent mechanism involving the trigeminovascular system. Here, we examine whether chronic environmental irritant exposure sensitizes the trigeminovascular system. METHODS: Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for four days prior to meningeal blood flow measurements. Some animals were injected daily with a TRPA1 antagonist, AP-18, or vehicle prior to inhalation exposure. Trigeminal ganglia were isolated following blood flow measurements for immunocytochemistry and/or qPCR determination of TRPV1, TRPA1 and CGRP levels. RESULTS: Acrolein inhalation exposure potentiated blood flow responses both to TRPA1 and TRPV1 agonists compared to room air. Acrolein exposure did not alter TRPV1 or TRPA1 mRNA levels or TRPV1 or CGRP immunoreactive cell counts in the trigeminal ganglion. Acrolein sensitization of trigeminovascular responses to a TRPA1 agonist was attenuated by pre-treatment with AP-18. INTERPRETATION: These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure.

Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants.

Headache is the most common symptom associated with air pollution, but little is understood about the underlying mechanism. Nasal administration of environmental irritants activates the trigeminovascular system by a TRPA1-dependent process. This report addresses questions about the anatomical pathway involved and the function of TRP channels in this pathway. TRPV1 and TRPA1 are frequently co-localized and interact to modulate function in sensory neurons. We demonstrate here that resiniferatoxin ablation of TRPV1 expressing neurons significantly reduces meningeal blood flow responses to nasal administration of both TRPV1 and TRPA1 agonists. Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia. Sensory neurons of the trigeminal ganglia innervate the nasal epithelium and the meninges, but the mechanism and anatomical route by which nasal administration evokes meningeal vasodilatation is unclear. Double retrograde labeling from the nose and meninges reveals no co-localization of fluorescent label, however nasal and meningeal labeled cells are located in close proximity to each other within the trigeminal ganglion. Our data demonstrate that TRPV1 expressing neurons are important for TRPA1 responses in the nasal-meningeal pathway. Our data also suggest that the nasal-meningeal pathway is not primarily by axon reflex, but may instead result from intraganglionic transmission.

K(ATP) channel openers in the trigeminovascular system.

BACKGROUND: The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involves opening of vascular or neuronal K(ATP) channels and mast cell degranulation. Using rat as a model, we studied the molecular presence of K(ATP) channels in the trigeminovascular system. Furthermore, we examined whether K(ATP) channel openers stimulate the in vitro release of CGRP and whether they degranulate dural mast cells. METHODS: mRNA and protein expression of K(ATP) channel subunits were studied in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) by qPCR and western blotting. In vitro CGRP release was studied after application of levcromakalim (1 µM) and diazoxide (10 µM) to freshly isolated rat dura mater, TG and TNC. Rat dural mast cells were challenged in situ with levcromakalim (10(-5) M) to study its potential degranulation effect. RESULTS: mRNA and protein of K(ATP) channel subunits Kir6.1, Kir6.2, SUR1 and SUR2B were identified in the TG and TNC. K(ATP) channel openers did not release or inhibit capsaicin-induced CGRP release from dura mater, TG or TNC. They did also not induce dural mast cell degranulation. CONCLUSIONS: K(ATP) channel openers do not interact with CGRP release or mast cell degranulation. Activation of these channels in the CNS is antinociceptive and therefore cannot explain the headache induced by K(ATP) channel openers. Thus, they are likely to induce headache by interaction with extracerebral K(ATP) channels, probably the SUR2B isoforms.

Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system.

AIM: To use an animal model to test whether migraine pain arises peripherally or centrally. METHODS: We monitored the spontaneous and evoked activity of second-order trigeminovascular neurons in rats to test whether traffic increased following a potential migraine trigger (cortical spreading depression, CSD) and by what mechanism any such change was mediated. RESULTS: Neurons (n = 33) responded to stimulation of the dura mater and facial skin with A-δ latencies. They were spontaneously active with a discharge rate of 6.1 ± 6.4 discharges s(-1). Injection of 10 µg lignocaine into the trigeminal ganglion produced a fully reversible reduction of the spontaneous discharge rate of neurons. Neuronal discharge rate returned to normal by 90 min. Lignocaine reduced the evoked responses of neurons to dural stimulation to 37% and to facial skin stimulation to 53% of control. Induction of CSD by cortical injection of KCl increased the spontaneous discharge rate of neurons from 2.9 to 16.3 discharges s(-1) at 20 min post CSD. Injection of 10 µg lignocaine into the trigeminal ganglion at this time failed to arrest or reverse this increase. Injection of lignocaine prior to the initiation of CSD failed to prevent the subsequent development of CSD-induced increases in discharge rates. CONCLUSIONS: These results suggest that there is a continuous baseline traffic in primary trigeminovascular fibres and that CSD does not act to increase this traffic by a peripheral action alone - rather, it must produce some of its effect by a mechanism intrinsic to the central nervous system. Thus the pain of migraine may not always be the result of peripheral sensory stimulation, but may also arise by a central mechanism.

An fMRI case report of photophobia: activation of the trigeminal nociceptive pathway.

Photophobia, or painful oversensitivity to light, occurs in a number of clinical conditions, which range from superficial eye irritation to meningitis. In this case study, a healthy subject with transient photophobia (induced by the overuse of contact lenses) was examined using functional magnetic resonance imaging (fMRI). While being scanned in a darkened environment, the subject was presented with intermittent 6-s blocks of bright light. The subject was scanned twice, once during his photophobic state and once after recovery. The subject reported that the visual stimuli produced pain (pain intensity=3/10 and unpleasantness=7/10) only during the photophobic state. During photophobia, specific activation patterns in the trigeminal system were seen at the level of the trigeminal ganglion, trigeminal nucleus caudalis, and ventroposteromedial thalamus. The anterior cingulate cortex, a brain structure associated with unpleasantness, was also active during photophobia. After recovery from photophobia, no significant activations were detected in these areas. This study may contribute to a better understanding of the pathways involved in photophobia in the human condition.

Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution.

Calcitonin gene-related peptide (CGRP) is a key mediator in primary headaches including migraine. Animal models of meningeal nociception demonstrate both peripheral and central CGRP effects; however, the target structures remain unclear. To study the distribution of CGRP receptors in the rat trigeminovascular system we used antibodies recognizing two components of the CGRP receptor, the calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1). In the cranial dura mater, CLR and RAMP1 immunoreactivity (-ir) was found within arterial blood vessels, mononuclear cells, and Schwann cells, but not sensory axons. In the trigeminal ganglion, besides Schwann and satellite cells, CLR- and RAMP1-ir was found in subpopulations of CGRP-ir neurons where colocalization of CGRP- and RAMP1-ir was very rare ( approximately 0.6%). CLR- and RAMP1-ir was present on central, but not peripheral, axons. In the spinal trigeminal nucleus, CLR- and RAMP1-ir was localized to "glomerular structures," partly colocalized with CGRP-ir. However, CLR- and RAMP1-ir was lacking in central glia and neuronal cell bodies. We conclude that CGRP receptors are associated with structural targets of known CGRP effects (vasodilation, mast cell degranulation) and targets of unknown function (Schwann cells). In the spinal trigeminal nucleus, CGRP receptors are probably located on neuronal processes, including primary afferent endings, suggesting involvement in presynaptic regulation of nociceptive transmission. Thus, in the trigeminovascular system CGRP receptor localization suggests multiple targets for CGRP in the pathogenesis of primary headaches.

Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig.

Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca(2+) removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.

Arteria trigeminal persistente y VI par craneal aislado / Persistent trigeminal artery and isolated sixth cranial nerve

No disponible

Hallazgos radiológicos de la arteria trigeminal persistente sintomática y asintomática / Radiological findings in symptomatic and asymptomatic persistent trigeminal artery

No disponible

No disponible

Hyperform remodeling balloon for the balloon occlusion test of persistent primitive trigeminal artery aneurysm - case report.

A 17-year-old woman presented with a rare aneurysm at the junction of the persistent primitive trigeminal artery (PPTA) and the internal carotid artery (ICA) manifesting as left abducens nerve paresis. The aneurysm and the ICA were both successfully occluded with coils. The balloon occlusion test used the HyperForm balloon microcatheter to seal the PPTA and ICA, which is very important to determine the optimal treatment strategy for a PPTA aneurysm.

Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system.

Activation of the trigeminovascular pain signalling system appears involved in migraine pathophysiology. However, the molecular mechanisms are only partially known. Stimulation of cAMP and cGMP production as well as inhibition of their breakdown induce migraine-like headache. Additionally, migraine may be associated with mutations in ion channels. The aim of the present study was to describe the expression of phosphodiesterase 3 (PDE3) and 5 (PDE5) and cyclic nucleotide-gated ion channels (CNG) in cerebral arteries, meninges, and the trigeminal ganglion. mRNA for PDE and CNG was determined in the rat middle cerebral artery, basilar artery, trigeminal ganglion, and dura mater using real-time PCR. PDE and CNG proteins were identified using Western blot. For comparison, rat aorta and mesenteric artery were analysed. PDE3A, PDE3B, and PDE5A mRNA were detected in all tissues examined except for PDE3A mRNA in dura mater and the trigeminal ganglion. PDE5A and PDE3A protein expression was present in both cerebral and peripheral arteries, whereas PDE3B protein was present only in the cerebral arteries. The CNGA4 and B1 subunit mRNAs were detected in cerebral arteries and CNGA2 also in the mesenteric artery. CNGA2 and A3 proteins were found in cerebral arteries and dura and CNGA1, CNGA2 and CNGA3 in the trigeminal ganglion. In conclusion, PDE3A, PDE3B, PDE5A, and five CNG subunits were expressed in several components of the trigeminovascular system of the rat. This suggests that modulation of cAMP and cGMP levels by PDE and activation of CNG may play a role in trigeminovascular pain signalling leading to migraine headache.

Chronological alterations of P2X3 receptor expression in the trigeminal ganglion after ischaemic insult in the Mongolian gerbil.

P2X receptors play a role in the transduction of sensory signals like pain. Few studies have been undertaken on altered P2X(3) receptor (P2X3) expression in sensory neurones after peripheral nerve injury. In the present study, we investigated chronological alterations in P2X3 immunoreactivity and its protein content in the trigeminal ganglion after ischaemic insult in the Mongolian gerbil. In the sham-operated group, P2X3-immunoreactive neurones were found abundantly in small- and medium-sized neurones. From 1 day after ischaemic insult, the number of P2X3-immunoreactive neurones decreased significantly. At 5 days after ischaemic insult, P2X3 immunoreactivity was observed in few neurones, but its immunoreactivity was weak. However, the number of cresyl violet-positive neurones was unchanged throughout this period in all groups. These results suggest that transient trigeminal ganglion ischaemia may provoke a decrease of P2X3 expression and its protein content, and that this down-regulation of P2X3 may be related to the altered pain and thermal sensation without being associated with a transient ischaemic insult.

Distribution of myelinated and unmyelinated nerve fibers and their possible role in blood flow control in crotaline snake infrared receptor organs.

We used transmission electron microscopic montages to examine the composition of nerve bundles serving the infrared pit organs of two species of crotaline snakes, Agkistrodon blomhoffii and A. brevicaudus. In the three main bundles, the myelinated fibers totaled 2,200-3,700, and unmyelinated fibers 2,400. We also discovered for the first time two accessory bundles composed almost entirely of unmyelinated fibers running alongside the main bundles, containing an average total of 3,300 unmyelinated fibers vs. an average of 10 myelinated fibers. Thus, the average total of unmyelinated fibers was nearly twice that of myelinated fibers. To study the nature of the unmyelinated fibers, we did double staining immunohistochemistry with antibodies for substance P (SP) and vasoactive intestinal polypeptide (VIP) in combination with and without capsaicin pretreatment. SP and VIP immunoreactive varicose fibers ran straight toward the center of the pit membrane in parallel with arterioles and venules, and also formed a dense network around the periphery of the membrane. There were three types of fibers: fibers containing only SP, fibers containing only VIP, and fibers containing both peptides. SP-only fibers were distributed singly throughout the pit membrane and in small bundles around the periphery. SP+VIP fibers were distributed sparsely in the pit membrane and around its periphery. VIP-only fibers were distributed throughout the pit membrane and were of smaller diameter than SP and SP+VIP fibers. After treatment with capsaicin, most of the three types of varicose fibers disappeared from the central part of the pit membrane, but those around the periphery remained unaffected. The capsaicin-sensitive fibers may be unmyelinated sensory types, and the unaffected ones may be autonomic nerve fibers.