TY - JOUR. T1 - Prevention of stress- or nitric oxide donor-induced medication overuse headache by a calcitonin gene-related peptide antibody in rodents. AU - Kopruszinski, Caroline Machado. AU - Xie, Jennifer Yanhua. AU - Eyde, Nathan Mackenzie. AU - Remeniuk, Bethany. AU - Walter, Sarah. AU - Stratton, Jennifer. AU - Bigal, Marcelo. AU - Chichorro, Juliana Geremias. AU - Dodick, David. AU - Porreca, Frank. PY - 2017/5/1. Y1 - 2017/5/1. N2 - Objective The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. Methods Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP ...

article{de44453f-818c-4e8d-b33b-fbdcb94ad5df, abstract = {,p,Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in ...

Numerous studies have shown that severing the dorsal roots, ie, the afferent nerves proximal to the dorsal root ganglia, reduces the number of substance P- and calcitonin gene-related peptide-containing nerves in the dorsal horn.21 There are few studies examining the effects of DRX on peripheral afferent innervation. However, there are reports showing that DRX at T6-L2 and L6/S1 reduced the number of substance P- and calcitonin gene-related peptide-containing nerves around the hepatic artery and portal vein22 and in urinary bladder,23 respectively. Therefore, we examined whether the responsiveness of afferent renal nerves was altered by DRX. Three weeks after DRX, increasing renal pelvic pressure failed to increase ARNA. The lack of ARNA responses in DRX rats was even more conspicuous considering that the rats were fed the HNa diet. In agreement with our previous studies,5 increasing renal pelvic pressure resulted in marked increases in ARNA in the sham-DRX rats fed an HNa diet. Further studies ...

The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP of human knee OA patients have not been examined. IFFP and synovial (SYN) tissues were harvested from 100 individuals with radiographic knee OA (unilateral Kellgren/Lawrence [K/L] grades 2-4) during total knee arthroplasty and subjected to immunohistochemical analysis for CGRP localization. In addition, the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2) in the collected tissues were evaluated and compared using real-time PCR analysis of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among

The trigeminal vascular system is a key player in the pathophysiology of migraine. Migraines are thought to be triggered when internal or environmental factors are of sufficient intensity to initiate the hyper excitement and activation of the trigeminal nerves. This activation provokes the release of neuroinflammatory mediators resulting in neurogenic inflammation, vasodilation, nociceptor activation, and propagation of pain response.. Some of the most important neuropeptides released in migraine attacks are Calcitonin Gene Related Peptide (CGRP), Substance P, and Serotonin.. Calcitonin Gene Related Peptide (CGRP). Migraine treatment has almost always relied on re-purposing medication developed to treat other conditions. However, the past decade has been tremendous for discoveries in migraine research and breakthroughs in migraine therapy. The aforementioned inflammatory neuropeptide Calcitonin Gene Related Peptide (CGRP) has played a major role in this march towards bespoke, novel targeted ...

article{416df13f-d0c5-43ac-a266-e7fbe6b94912, abstract = {,p,Background: Calcitonin gene-related peptide (CGRP) is a neuronal transmitter present in intracranial sensory nerves, where it is involved in migraine pathophysiology as well as other biological functions. Recently, the fully human monoclonal antibody erenumab (AMG 334), which targets the canonical calcitonin gene-related peptide receptor, showed significant prophylactic efficacy and favourable safety in phase II and III clinical trials for episodic and chronic migraine and is now approved for migraine prevention in several countries. Objective: Given that calcitonin gene-related peptide can mediate vasodilation, we investigated the effect of erenumab on vasoactive responses in the presence or absence of various vasodilatory and vasocontractile mediators in a model using isolated human cerebral and meningeal arteries. Methods: Ring segments of human isolated cerebral and meningeal arteries were mounted in a sensitive myograph. On ...

The main olfactory bulb (OB) is made up of several concentric layers, forming circuitries often involving dendro-dendritic synapses. Important interactions between OB neurons occur in the external plexiform layer (EPL), where dendrites of tufted and Van Gehuchten cells form synapses with dendrites of deeper lying mitral, tufted, and granule cells. OB neurons display a variety of neurotransmitters. Here, the focus is on calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide transmitter that is widely distributed in the central and peripheral nervous system. In the OB, CGRP-immunoreactive (ir) cell bodies were mostly observed in the mitral cell layer (MCL) of normal mice, and their number increased following colchicine treatment. Sparsely distributed CGRP-ir cell bodies were also found in the EPL and granular cell layer. Double-immunofluorescence experiments revealed a lack of co-localization between CGRP-like immunoreactivity (LI) and corticotropin-releasing factor- or galanin-LI, ...

Migraine is a debilitating neurological condition involving the neuropeptide calcitonin gene-related peptide (CGRP). The overall objective of this project is to...

Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery. Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design. Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p | 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable

Tozzi A, de Iure A, Di Filippo M, Costa C, Caproni S, Pisani A, Bonsi P, Picconi B, Cupini LM, Materazzi S, Geppetti P, Sarchielli P, Calabresi ...

To the Editor: I read with interest the ESBY study (Electrical Stimulation versus coronary artery BYpass surgery in severe angina pectoris) by Mannheimer et al.1 They found that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe angina pectoris and concluded that CABG and SCS are equivalent methods in terms of symptom relief.. In a previous report,2 these authors showed that myocardial extraction of β-endorphin during control atrial pacing changed to release at the maximum pacing rate during SCS. Furthermore, their results indicate local myocardial turnover of β-endorphin, leuenkephalin, and calcitonin-gene-related peptide. Han et al3 found that electroacupuncture of different frequencies was able to activate different opioid systems in the spinal cord of the rat: low frequency (2 Hz) for [Met5 ]enkephalin release and high frequency (100 Hz) for dynorphin A release. An optimal combination of electroacupuncture parameters is now under study for maximal release of ...

TY - JOUR. T1 - Role of ATP-sensitive K+ channels in CGRP-induced dilatation of basilar artery in vivo. AU - Kitazono, Takanari. AU - Heistad, D. D.. AU - Faraci, F. M.. PY - 1993/9/22. Y1 - 1993/9/22. N2 - Stimulation of adenylate cyclase appears to activate ATP-sensitive K+ channels in the basilar artery. We tested the hypothesis that calcitonin gene-related peptide (CGRP), which increases intracellular adenosine 3,5- cyclic monophosphate (cAMP) levels, activates ATP-sensitive K+ channels and thereby causes vasodilatation. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to CGRP in vivo. We also examined responses of the artery to another vasoactive peptide, vasoactive intestinal peptide (VIP). Topical application of CGRP (10-11 to 10-8 M) increased diameter of the basilar artery. Responses of the basilar artery to CGRP were almost abolished by a CGRP1 receptor antagonist, CGRP-(8-37). Vasodilatation in response to VIP was much smaller than that ...

Peptides , Calcitonin Related Peptides; Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM) and amylin belong to a unique group of calcitonin-related peptide hormones important for homeostasis in diverse tissues. Calcitonin, a 32-amino acid peptide hormone, is essential for calcium balance, whereas CGRP and ADM are important for neurotransmission and cardiovascular and respiratory function. Calcitonin regulates mineral balance by controlling blood concentrations of calcium and phosphorus metabolism and can cause hypercalcemia. An increase in the serum calcium level is known to stimulate calcitonin secretion. In mammals, the major source of calcitonin is from the parafollicular or C cells in the thyroid gland, but it is also synthesized in a wide variety of other tissues, including the lung and intestinal tract. Calcitonin contains a single disulfide bond, which causes the amino terminus to assume the shape of a ring. The calcitonin family of peptides act through G-protein protein coupled

The trigeminal ganglion plays a key role in primary headache pathophysiology. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal neurons that form C-fibers and A-fibers, respectively. In acute migraine and cluster headache attacks, there is release of CGRP into the cranial venous outflow. In addition, intravenous CGRP can induce migraine-like symptoms in migraine patients. These findings led to the development of anti-migraine therapies that inhibit CGRP action. Currently, CGRP receptor antagonists, the gepants, and monoclonal antibodies towards CGRP and the CGRP receptor are all showing positive relief of acute and chronic migraine in clinical trials ...

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the ...

B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freunds adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+-activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory ...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral anti-diabetic drugs, implicated in pleiotropic secondary cardioprotective effects. The aim of the study was to unveil the unknown and possible cardioprotective targets that can be exerted by sitagliptin (Sitg) against ischemia-reperfusion (I/R) injury. Male wistar rats received 2 weeks’ Sitg oral treatment of different doses (25, 50, 100, and 150 mg/kg/day), or saline as a Control. Hearts were then isolated and subjected to two different I/R injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for infarct size (IS) measurement, or: 10 min perfusion, 45 min regional ischemia and 10 min reperfusion for biochemical analysis: nitric oxide synthases (NOSs) and DPP-4 activity, glucagon-like peptide-1 (GLP-1), Calcium, transient receptor potential vanilloid (TRPV)-1 and calcitonin gene-related peptide (CGRP) levels, transient receptor potential canonical (TRPC)-1 and e-NOS protein expression. NOS inhibitor (l

Calcitonin is a circulating polypeptide that inhibits bone resorption by inducing both quiescence (Q effect) and retraction (R effect) in osteoclasts. Two structurally related members of the calcitonin gene peptide family, calcitonin gene-related peptide (CGRP) and amylin, inhibit osteoclastic bone resorption selectively via the Q effect. In the present study, we have made measurements of cell spread area in response to the application of amylin, CGRP and a peptide fragment of CGRP, CGRP-(Val8Phe37). We found that, over a wide concentration range (50 pmol/l to 2.5 mumol/l), the selective Q effect agonists did not produce an R effect. Furthermore, the peptides, when used at a 50-fold higher molar concentration than calcitonin, did not antagonize calcitonin-induced cell retraction. Additionally, experiments designed to measure changes in the intracellular free calcium concentration ([Ca2+]i) in single osteoclasts revealed that, unlike calcitonin, the non-calcitonin Q effect agonists did not produce a rise

PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the December 2017 issue here.. ...

Human APP PicoKine™ ELISA Kit (Amyloid beta A4 protein)...: cell biology- apoptosis- neural signal transduction- nervous system development. Bazı Hormon Belirteçleri için Yeni Çıkan ELISA Kitleri: -Alpha (aCGRP) Calcitonin Gene-Related Peptide ELISA Kit. -Beta(bCGRP) Calcitonin Gene-Related Peptide ELISA Kit. -Bradykinin ELISA Kit. -Caerulein ELISA Kit. -Dynorphin ELISA Kit. -ELABELA ELISA kit. -Enkephalin ELISA Kit. -Exendin-4 ELISA Kit. -Galanin ELISA Kit. -Hepsidin 25 ELISA Kit. -LHRH ELISA Kit. -Liraglutide ELISA Kit. -Pancreastatin ELISA Kit. -Secretin ELISA Kit. -TIP39(Tuberoinfundibular peptide39) ELISA Kit. -VIF ( Vasoconstriction Inhibiting Factor) ELISA Kit -VIP ( Vasoactive Interstinal Peptide) ELISA Kit Yeni ÇIKAN ELISA Kitleri ve Klinik Eşleştirmeleri: *Human Afamin ELISA kit: AFM is a member of the albumin gene family: Diabetology - Other Relevant Products, Energy metabolism and body weight regulation. *Human Cystatin B ELISA: Autoimmunity, Oncolog. *Human Cysteine-Rich ...

A female is considered of childbearing potential unless she is post menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration.. Reliable methods of contraception are: Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; or, History of bilateral tubal ligation; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion) in use at least 30 days prior to study drug ...

Due to a dismal prognosis of advanced non- small cell lung cancer (NSCLC), novel screening tools and more effective treatments are clearly needed. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor. Endothelin-1 (ET-1) and alpha calcitonin gene related peptides (CGRP) are promising biomarkers for tumor angiogenesis. The aims of our study were to evaluate angiogenic and prognostic impacts of VEGF, ET-1, CGRP and other laboratory parameters? serum levels in advanced NSCLC patients. Sixty seven patiens (62 male, 5 female) and twenty healhty (16 male, 4 female) volunteers were included in this study. Demographical, laboratory data and serum levels of VEGF, ET-1 and CGRP were compared for two groups. Patients presented significantly higher serum VEGF (p=0.000), lower serum thyroid stimulating hormone (TSH), albumin and hemoglobin levels than controls (p=0.000, p=0.014 and p=0.001 respectively). Leukocytosis, thrombocytosis, high levels of C reactive peptide (CRP) and ...

It has been proposed that substance P and calcitonin gene-related peptide (CGRP) are up-regulated in low-threshold myelinated primary afferents following certain types of nerve injury, and that release of substance P from these afferents contributes to the resulting tactile allodynia. To test this hypothesis, we looked for neuropeptides in Aβ primary afferent terminals in the ipsilateral gracile nucleus and spinal dorsal horn in three nerve injury models: sciatic nerve transection (SNT), spinal nerve ligation (SNL) and chronic constriction injury (CCI). We also looked for evidence of neurokinin 1 (NK1) receptor internalisation in the dorsal horn following electrical stimulation of Aβ afferents. We found no evidence of either substance P or CGRP expression in injured Aβ terminals in the spinal cord in any of the models. Although substance P was not detected in terminals of injured afferents in the gracile nucleus, CGRP was expressed in between 32 and 68% of these terminals, with a ...

It has been proposed that substance P and calcitonin gene-related peptide (CGRP) are upregulated in low-threshold myelinated primary afferents after certain types of nerve injury, and that release of substance P from these afferents contributes to the resulting tactile allodynia. To test this hypothesis, we looked for neuropeptides in Aβ primary afferent terminals in the ipsilateral gracile nucleus and spinal dorsal horn in three nerve injury models: sciatic nerve transection (SNT), spinal nerve ligation (SNL), and chronic constriction injury (CCI). We also looked for evidence of neurokinin 1 (NK1) receptor internalization in the dorsal horn after electrical stimulation of Aβ afferents. We found no evidence of either substance P or CGRP expression in injured Aβ terminals in the spinal cord in any of the models. Although substance P was not detected in terminals of injured afferents in the gracile nucleus, CGRP was expressed in between 32 and 68% of these terminals, with a significantly higher ...

CGRP (Calcitonin Gene Related Peptide) is a neuropeptide which is released into the blood stream during a migraine attack and it has a central role in the underlying mechanisms of a migraine attack.. Recent results from clinical trials targeting CGRP are encouraging and the drugs are now entering phase 3 late stage clinical trials to further evaluate the benefits and safety of these new therapies.. In this video clip at the European Academy of Neurology Congress 2016, Prof. Peter Goadsby discusses the rationale for using CGRP antibodies in the treatment of migraine and the study findings so far ...

Calcitonin gene-related peptide (CGRP) receptors were solubilized from rat cerebellum membranes in an active, stable, and guanine nucleotide-sensitive form by using digitonin. Nearly 90% of membrane CGRP receptors and 50% of membrane protein were solubilized by digitonin treatment of cerebellum membranes. Binding of 125ICGRP to soluble receptors was specific, saturable, of high affinity, and reversible. Scatchard analysis of the saturation binding data revealed a homogeneous population of binding sites with a Kd of 178 +/- 42 pM and a Bmax of 201 +/- 17 fmol/mg of protein. Binding of 125ICGRP to soluble receptors was inhibited nearly 60% by guanosine-5-O-(3-thio)triphosphate (GTP gamma S) (100 microM), suggesting coupling of receptors with guanine nucleotide-binding proteins (G proteins) to form high affinity binding sites. Antiserum against the amino-terminal region of Gs alpha immunoprecipitated a significant portion of soluble CGRP receptors, indicating association of receptors with Gs ...

TY - JOUR. T1 - Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture. AU - Vasko, M. R.. AU - Campbell, W. B.. AU - Waite, K. J.. PY - 1994/8/1. Y1 - 1994/8/1. N2 - Prostaglandins are known to enhance the inflammatory and nociceptive actions of other chemical mediators of inflammation such as bradykinin. One possible mechanism for this sensitizing action is that prostanoids augment the release of neuroactive substances from sensory neurons. To initially test this hypothesis, we examined whether selected prostaglandins could enhance the resting or bradykinin-evoked release of immunoreactive substance P (iSP) and/or immunoreactive calcitonin gene-related peptide (iCGRP) from sensory neurons in culture. Bradykinin alone causes a concentration-dependent increase in the release of iSP and iCGRP from isolated sensory neurons, and this action is abolished in the absence of extracellular calcium. Pretreating the neurons with PGE2 (10 nM to 1 μM) ...

Definition of vasodilator nerve in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is vasodilator nerve? Meaning of vasodilator nerve as a legal term. What does vasodilator nerve mean in law?

Background. Electrophysiological studies in the mammalian kidney have identified two major classes of sensory receptors of the afferent renal nerves; chemoreceptors (CR) and mechanoreceptors (MR). The localization of calcitonin gene-related peptide (CGRP) and substance P (SP) in these renal pelvic sensory neurons provides an anatomical basis for a possible functional interaction between the two neuropeptides and SP receptor. The present study was performed to examine the possible changes in the responsiveness of renal sensory SP and CGRP receptors in rats with streptozotocin (STZ)-induced diabetes mellitus. Due to the crucial role of renal pelvic SP and CGRP receptors in the activation of renal sensory neurons by various stimuli, we examined whether the responsiveness of MR or CR activation and the dorsal root ganglia content of neuropeptides and neurokinin 1 receptors (NK(1)R) were altered in diabetic rats compared with non-diabetic rats. Methods. Afferent renal nerve activity (ARNA) was ...

This book contains reviews by a renowned group of clinicians and scientists, which consider in great depth the potential involvement of neurogenic inflammation in the pathogenesis of migraine and inhibition of this putative mechanism as a possible mode of action of antimigraine medications. The authors carefully consider current and future potential therapeutic approaches for the abortive as well as preventive treatment of migraine. The pioneering work by Professor Michael A. Moskowitzs group at Harvard gave rise to the neurogenic hypothesis of migraine pathogenesis and to an intel- lectual framework for many aspects of migraine research through a detailed phar- macological characterization of the trigeminovascular system. This knowledge then spurred detailed research worldwide into the roles of the dural vasculature, trigem- inal nerve fibers, and sensory neuropeptides, such as substance P and calcitonin gene-related peptide, in migraine. Similar in-depth investigations have not been made of the

Author(s): Mitsikostas, Dimos D; Rapoport, Alan M | Abstract: Migraine is a common, chronic disorder of the brain causing much disability, as well as personal, familial and societal impact. Several oral preventive agents are available in different countries for the prevention of migraine, but none have performed better than 50% improvement in 50% of patients in a clinical trial. Additionally, each has various possible adverse events making their tolerability less than optimal. Recently, three monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) ligand (LY2951742, ALD403 and TEV-48125) and one targeting the CGRP receptor (AMG 334) have completed phase 2 trials, and the results have been reported. These early results show them all to be somewhat more effective than placebo, with no serious adverse events. Three have been studied for episodic migraine, and only TEV-48125 has been studied for both high frequency episodic and chronic migraine. Moreover, preliminary data suggests that

Boehringer Ingelheim Pharmaceuticals olcegepant (BIBN 4096) is a selective Calcitonin Gene-Related Peptide (CGRP) antagonist, a new class of drugs in development for the treatment of acute migraine attacks. Olcegepant is undergoing phase II trials in Europe and the US, with preliminary results suggesting that CGRP antagonists may represent a potential new approach to the treatment of migraine.

Goldstein, Eric D., Mohammed K. Badi, and James F. Meschia. Treating chronic migraine in CADASIL with calcitonin gene-related peptide receptor antagonism. Neurology: Clinical Practice (2019): 10.1212/CPJ.0000000000000651. Web. 20 Sept2020. ...

We studied the presence of sensory nerves by immunohistochemistry in the interface membranes of hip prostheses after aseptic loosening. Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were analysed as was protein gene product (PGP) 9.5, a general marker for nerve fibr …

Images. Sensory nerve fiber sprouting and formation of neuroma-like structures in the painful geriatric arthritic knee joint. Schematic of a frontal view of a cross-sectioned mouse knee joint (A). The red square illustrates the synovial region from which the confocal images were obtained. Representative confocal images of calcitonin gene-related peptide (CGRP+), neurofilament 200 kDa (NF200+) sensory nerve fibers (yellow/orange) and growth associated protein (GAP43; marker of fibers undergo regeneration, yellow/orange) and DAPI labeled nuclei (blue) in knee joint sections (20 μm thick) of vehicle-injected (B,D,F) and CFA-injected (C,E,G ) mice. In vehicle-injected mice, a low level, regular pattern of innervation by CGRP+ and NF200+ fibers is observed in the synovial space of the knee joint. Twenty-eight days following the initial CFA injection, a significant number of CGRP+ and NF200+ nerve fibers have sprouted and have a disorganized appearance as compared to vehicle-injected mice. Note that, ...

Learn about Aimovig, Ajovy, Vyepti, Emgality, and Nurtec - medications called calcitonin gene-related peptide (CGRP) inhibitors for preventing chronic and episodic migraines.

Images. Sensory nerve fiber sprouting and formation of neuroma-like structures in the painful geriatric arthritic knee joint. Schematic of a frontal view of a cross-sectioned mouse knee joint (A). The red square illustrates the synovial region from which the confocal images were obtained. Representative confocal images of calcitonin gene-related peptide (CGRP+), neurofilament 200 kDa (NF200+) sensory nerve fibers (yellow/orange) and growth associated protein (GAP43; marker of fibers undergo regeneration, yellow/orange) and DAPI labeled nuclei (blue) in knee joint sections (20 μm thick) of vehicle-injected (B,D,F) and CFA-injected (C,E,G ) mice. In vehicle-injected mice, a low level, regular pattern of innervation by CGRP+ and NF200+ fibers is observed in the synovial space of the knee joint. Twenty-eight days following the initial CFA injection, a significant number of CGRP+ and NF200+ nerve fibers have sprouted and have a disorganized appearance as compared to vehicle-injected mice. Note that, ...

Dorsal root ganglia taken from animals with CCI were analyzed for alterations in mRNA levels encoding growth-associated protein-43 (GAP-43), calcitonin gene-related peptide (CGRP), galanin (GAL), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal polypeptide (VIP ...

As hartmann and waldinger offer a useful adjunct for almost 3 years. Intracavernous calcitonin gene-related peptide (cgrp) acts on the male and his colleagues (1945) seemed willing to trust either my health or mental state and depression problems. The philosopher aristotle (384382 b. C.. Figure 5 graphic representation of the specific needs of these cases. I probably had cfs (chronic fatigue syndrome) from puberty although this may indicate a need for invasive treatment; however, when the patient presented with a male patient may present days or undergo surgical insertion of a sense of obligation that once impotent, always impotent, as some degree or existence of this disorder (jannini & lenzi, 2003; laumann et al. If our hypothesis is another term used for examining deep structures by means of self-protection, protection of the case the blending of mind and the duration and origin of the. He and cathy saw a woman is expected to be a sign of caring while she has power in the literature ...

in Neuroscience (1992), 51(2), 401-10. In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not ... [more ▼]. In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum ...

The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract While the expression of TRPA1 has been investigated in a variety of tissues, up until today no Study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue, Reverse transcriptase PCR (RT-PCR) Was applied in order to identify messenger ribonuleic acid specifically encoding for TAPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of imnnunohistocheitical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA ...

Heterotopic ossification, defined as the formation of bone in abnormal anatomic locations, can be clinically insignificant or devastating and debilitating, depending on the site and duration of new bone formation. There are many causes of heterotopic ossification (HO), including soft tissue trauma, central nervous system injury, vasculopathies, arthropathies, and inheritance. One of the least understood components of HO is the interaction of the peripheral nervous system with the induction of this process. Recent work has shown that, upon traumatic injury, a cascade of events termed neurogenic inflammation is initiated, which involves the release of neuropeptides, such as substance P and calcitonin gene related peptide. Release of these peptides ultimately leads to the recruitment of activated platelets, mast cells, and neutrophils to the injury site. These cells appear to be involved with both remodeling of the nerve, as well as potentially recruiting additional cells from the bone marrow to ...

Antibodies blocking a specific neurotransmitter involved in migraines appear to relieve migraine headaches. Two studies presented at the annual meeting of the American Academy of Neurology reported on the use of antibodies to CGRP (calcitonin gene-related peptide) for the treatment of migraine headaches. These were relatively small, but highly scientific (randomized, double-blind, and placebo-controlled) studies.…

Title: The Role of Neuropeptides and Neurohormones in Neurogenic Cardiac Arrhythmias. VOLUME: 3 ISSUE: 3. Author(s):T. M. Saleh. Affiliation:Department of Biomedical Science, Atlantic Veterinary College, University of Prince Edward Island,Charlottetown, P.E.I., Canada, C1A 4P3.. Keywords:neurotensin, substance p, cholecystokinin, somatostatin, calcitonin gene-related peptide, estrogen, sympathetic, parasympathetic, baroreceptor reflex, arrhythmias. Abstract: The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been the focus of considerable research over the past 25 years. These gut peptides or reproductive hormones have been localized within nuclei responsible for the relay of visceral afferent information to the forebrain. The presence of peptides and hormones along the gut- or heart-brain continuum suggests that these neurochemicals do more than modulate the visceral processes of digestion and reproduction respectively. Numerous studies have shown ...

Analysts took a look at the data on Amgens latest Phase III for CGRP migraine drug erenumab (AMG334) and came away reassured, but perhaps a bit unimpressed. Heres Leerinks Geoffrey Porges: The data confirm the ample evidence from phase 2 trials that suggested that calcitonin gene-related peptide (CGRP) receptor blockade will provide the first-ever migraine targeted prevention pharmaceutical treatment. Both trials demonstrated the superiority of AMG334 to placebo on both the primary and secondary endpoints, as well as showing excellent safety and tolerability. While the data were not overwhelmingly positive (i.e., 60% of patients with 50% reduction in migraine days), they were consistent and durable, which should ensure widespread adoption by patients (provide pricing and payer processing allow it). Amgens erenumab appears to have shown a similar placebo adjusted effect as Alders (OP) Eptinezumab in phase 2 trials (1 day improvement of monthly migraines at week 12). The effect is lower than ...

The 37-amino acid peptide called amylin is a major component of the islet amyloid deposited in the pancreases of persons with type 2 diabetes mellitus. We report the isolation of a partial cDNA clone and a phage lambda genomic clone of the coding region of the amylin gene. The DNA sequence encodes a protein sequence identical to that of amylin isolated from the amyloid found in the diabetic pancreas and shows that amylin is likely to be synthesized as a precursor peptide, now named proamylin. We have demonstrated that the amylin gene is present on chromosome 12 and that it is probably transcribed in the islets of Langerhans. The sequences of the genes for amylin and the calcitonin gene-related peptides (CGRPs) show strong similarity, especially over their 5 coding regions, where both peptides have a conserved intramolecular disulfide bridge, and also over their 3 coding regions, where the presence of a glycine codon strongly suggests that the carboxyl-terminal residue of amylin, like that of CGRP, is

Cyclophosphamide- (CYP-) induced cystitis increases calcitonin gene-related peptide (CGRP) in the urinary bladder and cystometric fluid and the antioxidant, Tem

BACKGROUND: Migraine has been recognized as one of the leading causes of disability in the 2013 Global Burden of Disease Study and seriously affects the quality of patients life, current treatment options are not ideal. Monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) appear more promising for migraine because of considerably better effect and safety profiles. The objective of this study is to systematically assess the clinical efficacy and safety of CGRP-mAbs for migraine therapy. METHODS: A systematic literature search in PubMed, Cochrane Library and Baidu Scholar was performed to identify randomized controlled trials (RCTs), which compared the effect and safety of CGRP-mAbs with placebo on migraine. Regarding the efficacy, the reduction of monthly migraine days from baseline to weeks 1-4, 5-8, and 9-12; responder rates were extracted as the outcome measures of the effects of CGRP-mAbs. Regarding the safety, total adverse events, the main adverse events, ...

A low or a high dose of tetanus neurotoxin (TeNT) injected in the lateral rectus muscle of the cat causes respectively, functional block of inhibitory synapses only or of both inhibitory and excitatory synapses simultaneously in abducens neurons (González-Forero et al. [2003] J. Neurophysiol. 89:1878-1890). As a consequence, neuronal firing activity increases (at low dose) or decreases (at high dose). We investigated possible structural modifications of inhibitory synapses in response to these activity alterations induced by TeNT. We used immunofluorescence against postsynaptic (gephyrin) and presynaptic (vesicular γ-aminobutyric acid [GABA] transporter [VGAT]) markers of inhibitory synapses in combination with cell type markers for abducens motoneurons (calcitonin gene-related peptide or choline acetyltransferase) or internuclear neurons (calretinin). Seven days after high-dose treatment, the number of gephyrin-immunoreactive (IR) clusters per 100 μm of membrane perimeter was reduced on the soma of

electromechanical responses of cardiomyocytes to individual and combined components of ischemia. Can. J. Physiol. Pharmacol, 80: 1145-1157 2003.- Schaeffer, C., D. Vandroux, L. Thomassin, P. Athias, L. Rochette and J. L. Connat. Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK. Biochim Biophys Acta 1643(1-3): 65-73. 2004.- Chantome, A., A. Pance, N. Gauthier, D. Vandroux, J. Chenu, E. Solary, J. F. Jeannin and S. Reveneau. Casein kinase II-mediated phosphorylation of NF-kB p65 subunit enhances inducible nitric oxide synthase gene transcription in vivo. J Biol Chem. 279(23): 23953-60. 2004.- Gambert, S., S. Bes-Houtmann, D. Vandroux, C. Tissier, C. Vergely-Vandriesse, L. Rochette and P. Athias. Deep hypothermia during ischemia improves functional recovery and reduces free-radical generation in isolated reperfused rat heart. J Heart Lung Transplant 23(4): 487-91. 2004.- Vandroux, D., C. ...