scholarly journals Non-invasive dural stimulation in mice: A novel preclinical model of migraine

Cephalalgia ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 123-134 ◽  
Author(s):  
Carolina Christina Burgos-Vega ◽  
Lilyana D Quigley ◽  
Gabriela Trevisan dos Santos ◽  
Flora Yan ◽  
Marina Asiedu ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Interleukin 6 ◽  
Allyl Isothiocyanate ◽  
Low Ph ◽  
Injection Technique ◽  
Systemic Injection ◽  
Non Invasive ◽  
Inflammatory Soup

Background Migraine is characterized by a collection of neurological symptoms in the absence of injury or damage. However, several common preclinical migraine models require significant damage to the skull to stimulate the dura mater, the likely source of afferent signaling leading to head pain. The goal of this study was to determine whether dural stimulation can be performed in mice using an injection that does not cause injury or damage. Methods Using mice, injections of stimuli were administered to the dura mater through the soft tissue at the intersection between the lambdoidal and sagittal sutures. This technique did not require a permanent cannula nor did it cause damage to the skull or dura. Following injection of noxious stimuli, migraine-like behaviors were measured including cutaneous allodynia and facial grimace. The retrograde tracer fluorogold was applied onto the dura using the same injection technique to label trigeminal ganglion cell bodies, which were then testing in vitro using patch-clamp electrophysiology. Results Dural injection of allyl-isothiocyanate, low pH, interleukin-6, or inflammatory soup but not vehicles, led to cephalic/extracephalic allodynia. Facial grimace responses were also observed with allyl-isothiocyanate, pH 6.0, and interleukin-6. Stimulation with interleukin-6 causes priming to normally subthreshold pH 7.0 stimulation of the dura following resolution of the initial interleukin-6 behavior. Systemic injection of sumatriptan at the time of dural stimulation with inflammatory soup decreased the resulting cutaneous hypersensitivity. Trigeminal ganglion cell bodies retrogradely labeled from the dura had low pH-evoked currents similar to those generated by acid-sensing ion channels. Conclusion Non-invasive dural stimulation in mice can be used as a model of migraine in the absence of injury.

Calcitonin gene-related peptide receptors in rat trigeminal ganglion do not control spinal trigeminal activity

2012 ◽  
Vol 108 (2) ◽  
pp. 431-440 ◽  
Author(s):  
Oana Covasala ◽  
Sören L. Stirn ◽  
Stephanie Albrecht ◽  
Roberto De Col ◽  
Karl Messlinger
Keyword(s):  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Afferent Input ◽  
Nitric Oxide Donor ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Evoked Activity

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity of trigeminal afferents and hence of spinal trigeminal neurons. In anesthetized rats extracellular activity was recorded from neurons with meningeal afferent input in the spinal trigeminal nucleus caudalis. Mechanical stimuli were applied at regular intervals to receptive fields located in the exposed cranial dura mater. α-CGRP (10−5 M), the CGRP receptor antagonist olcegepant (10−3 M), or vehicle was injected through the infraorbital canal into the trigeminal ganglion. The injection of volumes caused transient discharges, but vehicle, CGRP, or olcegepant injection was not followed by significant changes in ongoing or mechanically evoked activity. In animals pretreated intravenously with the nitric oxide donor glyceryl trinitrate (GTN, 250 μg/kg) the mechanically evoked activity decreased after injection of CGRP and increased after injection of olcegepant. In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.

Maternal Serum Interleukin-6: A Non-Invasive Predictor of Histological Chorioamnionitis in Women with Preterm-Prelabor Rupture of Membranes

2018 ◽  
Vol 45 (3) ◽  
pp. 168-175 ◽  
Author(s):  
Raigam Jafet Martinez-Portilla ◽  
Ameth Hawkins-Villarreal ◽  
Pamela Alvarez-Ponce ◽  
Zarela Lizbeth Chinolla-Arellano ◽  
Ana Lisbeth Moreno-Espinosa ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Maternal Serum ◽  
Non Invasive ◽  
Prelabor Rupture Of Membranes

scholarly journals Applied Anatomy for Botulinum Toxin Injection in Cosmetic Interventions

2020 ◽  
Vol 8 (4) ◽  
pp. 336-343
Author(s):  
Ayman D’Souza ◽  
Chew Lip Ng
Keyword(s):  
Botulinum Toxin ◽  
Adverse Effects ◽  
Botulinum Toxin Injection ◽  
Injection Technique ◽  
Optimal Outcome ◽  
Applied Anatomy ◽  
Non Invasive ◽  
Facial Musculature ◽  
Upper Face ◽  
Facial Anatomy

Abstract Purpose of Review To provide the reader with a clear overview of facial anatomy as it relates to injection of botulinum toxin. Recent Findings The review suggests the presentation of multiple combinations of facial musculature, with the forehead, glabellar, and nasal base areas as particular areas of variation. Differences in musculature result in different wrinkling patterns; with age, these changes first become apparent in the upper face, particularly in the forehead and glabellar area. Summary Botulinum toxin is well suited to achieve the optimal outcome: it is popular, safe, and non-invasive and presents with few adverse effects. Though limited, when adverse effects do arise these are primarily related to poor injection technique, often fuelled by poor anatomical knowledge. For clinicians to achieve the best outcomes with botulinum toxin use, an understanding of the facial muscles’ anatomy, actions, and interactions is key. This paper discusses the broad and intricate detail regarding the key target muscles of botulinum toxin, based on both literature review and cadaveric dissection carried out by the authors.

An underrepresented majority: A systematic review utilizing allodynic criteria to examine the present scarcity of discrete animal models for episodic migraine

Cephalalgia ◽  
2020 ◽  
pp. 033310242096698
Author(s):  
Aidan Levine ◽  
Todd W Vanderah ◽  
Tally M Largent-Milnes
Keyword(s):  
Animal Models ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Episodic Migraine ◽  
Non Invasive ◽  
The Past ◽  
Inflammatory Soup ◽  
Distinct Disease ◽  
Post Traumatic ◽  
Episodic Migraineurs

Background Despite increasing evidence differentiating episodic and chronic migraine, little work has determined how currently utilized animal models of migraine best represent each distinct disease state. Aim In this review, we seek to characterize accepted preclinical models of migraine-like headache by their ability to recapitulate the clinical allodynic features of either episodic or chronic migraine. Methods From a search of the Pu bMed database for “animal models of migraine”, “headache models” and “preclinical migraine”, we identified approximately 80 recent (within the past 20 years) publications that utilized one of 10 different models for migraine research. Models reviewed fit into one of the following categories: Dural KCl application, direct electrical stimulation, nitroglycerin administration, inflammatory soup injection, CGRP injection, medication overuse, monogenic animals, post-traumatic headache, specific channel activation, and hormone manipulation. Recapitulation of clinical features including cephalic and extracephalic hypersensitivity were evaluated for each and compared. Discussion Episodic migraineurs comprise over half of the migraine population, yet the vast majority of current animal models of migraine appear to best represent chronic migraine states. While some of these models can be modified to reflect episodic migraine, there remains a need for non-invasive, validated models of episodic migraine to enhance the clinical translation of migraine research.

scholarly journals Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehmet S. Ozdas ◽  
Aagam S. Shah ◽  
Paul M. Johnson ◽  
Nisheet Patel ◽  
Markus Marks ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Drug Carriers ◽  
Mri Contrast Agents ◽  
Mri Contrast ◽  
Systemic Injection ◽  
Non Invasive ◽  
Brain Circuits ◽  
Cavitation Detection ◽  
The Brain ◽  
Target Effects

Abstract Non-invasive, molecularly-specific, focal modulation of brain circuits with low off-target effects can lead to breakthroughs in treatments of brain disorders. We systemically inject engineered ultrasound-controllable drug carriers and subsequently apply a novel two-component Aggregation and Uncaging Focused Ultrasound Sequence (AU-FUS) at the desired targets inside the brain. The first sequence aggregates drug carriers with millimeter-precision by orders of magnitude. The second sequence uncages the carrier’s cargo locally to achieve high target specificity without compromising the blood-brain barrier (BBB). Upon release from the carriers, drugs locally cross the intact BBB. We show circuit-specific manipulation of sensory signaling in motor cortex in rats by locally concentrating and releasing a GABAA receptor agonist from ultrasound-controlled carriers. Our approach uses orders of magnitude (1300x) less drug than is otherwise required by systemic injection and requires very low ultrasound pressures (20-fold below FDA safety limits for diagnostic imaging). We show that the BBB remains intact using passive cavitation detection (PCD), MRI-contrast agents and, importantly, also by sensitive fluorescent dye extravasation and immunohistochemistry.

Evidence for 5-HT1B/1D Receptors Mediating the Antimigraine Effect of Sumatriptan and Dihydroergotamine

Cephalalgia ◽  
1991 ◽  
Vol 11 (4) ◽  
pp. 165-168 ◽  
Author(s):  
Maria Gabriella Buzzi ◽  
Michael A Moskowitz
Keyword(s):  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Plasma Protein ◽  
Cell Activation ◽  
Rank Order ◽  
Plasma Extravasation ◽  
Protein Extravasation ◽  
Trigeminal Stimulation ◽  
Plasma Protein Extravasation ◽  
Pre Treatment

Neurogenic plasma extravasation, endothelial cell activation (increase in vesicle number and vacuole formation), platelet aggregation and adhesion, and mast cell degranulation occur selectively in postcapillary venules of the dura mater following electrical trigeminal ganglion stimulation, and are mediated by release of neuropeptides from perivascular unmyelinated C fibres. Pre-treatment with the antimigraine drugs dihydroergotamine and sumatriptan, two drugs that bind with high affinity to 5-HT1B/1D receptors, markedly attenuated plasma protein extravasation induced by electrical trigeminal ganglion stimulation. Trigeminal stimulation increased plasma calcitonin gene-related peptide levels in rat superior sagittal sinus. Pre-treatment with dihydroergotamine and, to a lesser extent, sumatriptan, attenuated this increase. Both drugs reduced morphological changes in post-capillary venules and mast cells within dura mater following electrical trigeminal ganglion stimulation. Plasma protein extravasation was selectively blocked in dura mater (but not in extracranial tissues) by pre-treatment with those receptor agonists showing a rank order of potency suggesting a 3-HT1B/1D interaction (5-CT > 5-BT > DHE > sumatriptan > 8-OH-DPAT). Pre-treatment with 5-HT2 and 5-HT3 antagonists was not effective. Taken together, these data are consistent with the interpretation that putative 5-HT-1B/1D receptors located on sensory fibres are coupled to inhibition of peptide release and blockade of neurogenic inflammation. An important therapeutic action of ergot alkaloids and sumatriptan in migraine headaches is so defined.

Combined retrograde tracing and enzyme/immunohistochemistry of trigeminal ganglion cell bodies innervating tooth pulps in the rat

Neuroscience ◽  
1989 ◽  
Vol 33 (1) ◽  
pp. 101-109 ◽  
Author(s):  
K. Fried ◽  
J. Arvidsson ◽  
B. Robertson ◽  
E. Brodin ◽  
E. Theodorsson
Keyword(s):  
Ganglion Cell ◽  
Trigeminal Ganglion ◽  
Retrograde Tracing

scholarly journals Toward Development of Neuron Specific Transduction After Systemic Delivery of Viral Vectors

2021 ◽  
Vol 12 ◽  
Author(s):  
Dylan J. Finneran ◽  
Ikenna P. Njoku ◽  
Diego Flores-Pazarin ◽  
Meghana R. Ranabothu ◽  
Kevin R. Nash ◽  
...  
Keyword(s):  
Viral Vectors ◽  
High Titer ◽  
Systemic Delivery ◽  
Adeno Associated Virus ◽  
Systemic Injection ◽  
Peripheral Tissues ◽  
Calcium Dependent ◽  
Non Invasive ◽  
Neuronal Tissues ◽  
Cag Promoter

Widespread transduction of the CNS with a single, non-invasive systemic injection of adeno-associated virus is now possible due to the creation of blood-brain barrier-permeable capsids. However, as these capsids are mutants of AAV9, they do not have specific neuronal tropism. Therefore, it is necessary to use genetic tools to restrict expression of the transgene to neuronal tissues. Here we compare the strength and specificity of two neuron-specific promoters, human synapsin 1 and mouse calmodulin/calcium dependent kinase II, to the ubiquitous CAG promoter. Administration of a high titer of virus is necessary for widespread CNS transduction. We observed the neuron-specific promoters drive comparable overall expression in the brain to the CAG promoter. Furthermore, the neuron-specific promoters confer significantly less transgene expression in peripheral tissues compared with the CAG promoter. Future experiments will utilize these delivery platforms to over-express the Alzheimer-associated pathological proteins amyloid-beta and tau to create mouse models without transgenesis.

“EVALUATION OF I-PRF INJECTION TECHNIQUE AS AN ALTERNATIVE FOR RECONSTRUCTION OF INTERDENTAL PAPILLAE - A PILOT STUDY

2021 ◽  
pp. 50-53
Author(s):  
Nikhila Chandramohan ◽  
Swetha A
Keyword(s):  
Surgical Techniques ◽  
Vital Role ◽  
Surgical Reconstruction ◽  
Injection Technique ◽  
Potent Inducer ◽  
Non Invasive ◽  
Total Growth ◽  
Interdental Papilla ◽  
Tissue Grafts ◽  
Periodontal Plastic Surgery

One of the most challenging and least predictable procedures in periodontal plastic surgery is the reconstruction of the lost interdental papilla. Preserving the integrity of the papillae is of utmost importance. Different variations of surgical procedures using connective tissue grafts have proved to be successful. Being less invasive in nature, non-surgical techniques such as hyaluronic acid injections have turned out to be a boon in this regard. Platelet concentrates like PRF & PRP have shown promising results when used in surgical reconstruction of the lost papilla. One of the recent advancements in PRF formulations is the injectable PRF which is a liquid concentrate encompassing higher leuckocyte numbers, which resulted in higher total growth factor release, requiring slower and shorter centrifugation speeds for preparation. i-PRF was shown to be a potent inducer of cell proliferation, migration and angiogenesis, inducer of higher broblast migration and expression of PDGF, TGF-β, and collagen,thereby playing a vital role in tissue regeneration. With the current understanding, this study was designed to investigate the efciency of iPRF in achieving interdental papillary enhancement. We have noted that mutilple doses of this autologous formulation prove to be a non-invasive alternative for the treatment of minimal interdental papilla loss; primarily Norland & Tarnow's Class I and to an extent Class II interdental papilla loss. Further validations of this technique are required

Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

Cephalalgia ◽  
2017 ◽  
Vol 38 (6) ◽  
pp. 1057-1070 ◽  
Author(s):  
Roshni Ramachandran ◽  
Sara Hougaard Pedersen ◽  
Dipak Vasantrao Amrutkar ◽  
Steffen Petersen ◽  
Julie Mie Jacobsen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Dorsal Root ◽  
Spinal Cord Dorsal Horn ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Extracellular Signal

Background A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis ( P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion ( P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min ( P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.

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