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Calcitonin gene-related peptide

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https://www.readbyqxmd.com/read/29160143/some-autonomic-deficits-of-acute-or-chronic-cervical-spinal-contusion-reversed-by-interim-brainstem-stimulation
#1
Alberto A Vitores, Stephanie S Sloley, Catalina Martinez, Melissa M Carballosa-Gautam, Ian D Hentall
Prolonged electrical stimulation of the hindbrain's nucleus raphe magnus (NRM) or its major midbrain input region, the periaqueductal gray (PAG), was previously found in rats to promote recovery from sensory-motor and histological deficits of acute thoracic spinal cord injury (SCI). Here, some visceral deficits of acute and chronic midline cervical (C5) contusion are similarly examined. Cranially implanted wireless stimulators delivered intermittent 8 Hz, 30-70 µA cathodal pulse trains to a brainstem microelectrode...
November 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29155208/inflammatory-renin-angiotensin-system-disruption-attenuates-sensory-hyperinnervation-and-mechanical-hypersensitivity-in-a-rat-model-of-provoked-vestibulodynia
#2
Anuradha Chakrabarty, Zhaohui Liao, Ying Mu, Peter G Smith
Vestibulodynia is characterized by peri-vaginal mechanical hypersensitivity, hyperinnervation, and abundant inflammatory cells expressing renin-angiotensin system proteins. We developed a tractable rat model of vestibulodynia to further assess the contributions of the renin-angiotensin system. Complete Freund's adjuvant (CFA) injected into the posterior vestibule induced marked vestibular hypersensitivity throughout a 7-day test period. Numbers of axons immunoreactive for PGP9.5, calcitonin gene-related peptide, and GFRα2 were increased...
November 15, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29154859/expression-of-cgrp-neurotransmitter-and-vascular-genesis-marker-mrna-is-age-dependent-in-superior-cervical-ganglia-of-senescence-accelerated-prone-mice
#3
Kazuyuki Mitsuoka, Takeshi Kikutani, Yoko Miwa, Iwao Sato
Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released from the superior cervical ganglion (SCG) and causes head and neck pain. The morphological properties of human SCG neurons, including neurotransmitter content, are altered during aging. However, morphological changes in CGRP in the SCG during aging are not known. Therefore, we investigated CGRP and other markers in the SCG during aging in an aging model of senescence-accelerated prone mouse (SAMP8) and senescence-accelerated resistant mice (SAMR1) using real-time RT-PCR mRNA analyses and in situ hybridization...
November 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29148033/4218t-c-polymorphism-associations-with-post-cesarean-patient-controlled-epidural-fentanyl-consumption-and-pain-perception
#4
W Xie, W Zhuang, L Chen, W Xie, C Jiang, N Liu
BACKGROUND: The utilization of intrathecal opioids is an efficacious component of post-cesarean section pain management. Given that growing evidence indicates that calcitonin gene-related peptide (CGRP) plays a key role in the development of peripheral sensitization and is associated with enhanced pain, we hypothesized that CGRP 4218T/C polymorphism is associated with the variability in fentanyl consumption for post-cesarean analgesia. METHODS: We recruited 548 patients who presented for elective cesarean delivery, and used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze CGRP 4218T/C polymorphism...
November 17, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#5
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#6
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29132068/secretoneurin-and-pe-11-immunoreactivity-in-the-human-dental-pulp
#7
René Steiner, Reiner Fischer-Colbrie, Athanasia Bletsa, Johannes Laimer, Josef Troger
OBJECTIVE: To explore whether there are differences in the concentration of the secretogranin II-derived peptide secretoneurin and the chromogranin B-derived peptide PE-11 between the healthy and inflamed human dental pulps. Furthermore, colocalization studies with calcitonin gene-related peptide were performed to confirm the sensory origin of the peptidergic nerves in the dental pulp. DESIGN: The concentrations of secretoneurin and PE-11 were determined by highly sensitive radioimmunoassays in extracts of dental pulps, the molecular form of secretoneurin immunoreactivities by RP-HPLC with subsequent radioimmunoassay and colocalization studies with calcitonin gene-related peptide were performed by double immunofluorescence...
November 9, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29131327/cgrp-and-ptx3-as-predictors-of-efficacy-of-onabotulinumtoxin-type-a-in-chronic-migraine-an-observational-study
#8
Clara Domínguez, Alba Vieites-Prado, María Pérez-Mato, Tomás Sobrino, Xiana Rodríguez-Osorio, Ana López, Francisco Campos, Francisco Martínez, José Castillo, Rogelio Leira
OBJECTIVE: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). BACKGROUND: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome...
November 13, 2017: Headache
https://www.readbyqxmd.com/read/29129515/amygdalin-improves-microcirculatory-disturbance-and-attenuates-pancreatic-fibrosis-by-regulating-the-expression-of-endothelin-1-and-calcitonin-gene-related-peptide-in-rats
#9
Xiangqun Zhang, Jiangong Hu, Yuzhen Zhuo, Lihua Cui, Caixia Li, Naiqiang Cui, Shukun Zhang
BACKGROUND: The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. METHODS: The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein...
November 9, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29116598/cgrp-monoclonal-antibodies-for-migraine-rationale-and-progress
#10
Hsiangkuo Yuan, Clinton G Lauritsen, Eric A Kaiser, Stephen D Silberstein
Calcitonin gene-related peptide (CGRP), a neuropeptide abundant in the trigeminal system and widely expressed in both the peripheral and central nervous systems, has recently emerged as a promising target for migraine management. While known as a potent arterial vasodilator, the role of CGRP in migraine is likely mediated by modulating nociception and sustaining neurogenic inflammation that leads to further peripheral and central pain sensitization. Functional blockade of CGRP, which involves either CGRP receptor antagonists or monoclonal antibodies (mAbs) to CGRP or its receptor, has recently shown clinical efficacy in migraine management...
November 7, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29110503/cgrp-a-target-for-preventive-therapy-in-migraine-and-cluster-headache-systematic-review-of-clinical-data
#11
Sabrina Khan, Astrid Olesen, Messoud Ashina
Introduction Migraine and cluster headache are challenging to manage, with no tailored preventive medications available. Targeting the calcitonin gene-related peptide (CGRP) pathway to treat these headaches may be the first focused therapeutic option to date, with the potential for promising efficacy. Methods We systematically searched PubMed and clinicaltrials.gov for randomized controlled trials investigating the preventive potential of monoclonal antibodies against the CGRP pathway in the treatment of migraine and cluster headache...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29108503/stress-during-development-of-experimental-endometriosis-influences-nerve-growth-and-disease-progression
#12
Marielly Cuevas, Myrella L Cruz, Antonio E Ramirez, Idhaliz Flores, Kenira J Thompson, Manuel Bayona, Michael W Vernon, Caroline B Appleyard
PURPOSE: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. METHODS: Endometriosis was surgically induced in female Sprague-Dawley rats by suturing uterine horn implants onto the small intestine mesentery...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29105468/-effect-of-manual-acupuncture-electroacupuncture-and-moxibustion-on-intestinal-motility-and-expression-of-enteric-nervous-activity-related-proteins-in-functional-constipation-rats
#13
Xin Zhang, Xuan-Ping Zhang, Yu-Zhu Du, Hai-Jiao Xing, Rui Jia, Li-Jia Pan, Jing Xu, Chun-Sheng Jia
OBJECTIVE: To compare the effect of manual acupuncture (MA), electroacupuncture (EA) and moxibustion interventions on intestinal motility and expression of enteric nervous activity related proteins calcitonin gene related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV 1) and proteinase activated receptor-4 (PAR-4) in colon tissue of rats with functional constipation (FC), so as to select a better intervention method for FC. METHODS: Sixty male SD rats were randomly divided into blank control (n=8), model (n=11), medication (n=8), MA (n=11), EA (n=11), and moxibustion (n=11) groups...
October 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29103805/a-genetically-defined-circuit-for-arousal-from-sleep-during-hypercapnia
#14
Satvinder Kaur, Joshua L Wang, Loris Ferrari, Stephen Thankachan, Daniel Kroeger, Anne Venner, Michael Lazarus, Andrew Wellman, Elda Arrigoni, Patrick M Fuller, Clifford B Saper
The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBel(CGRP) neurons caused wakefulness, whereas optogenetic inhibition of PBel(CGRP) neurons prevented arousal to CO2, but not to an acoustic tone or shaking...
October 24, 2017: Neuron
https://www.readbyqxmd.com/read/29100502/efficacy-of-nerve-growth-factor-antibody-in-a-knee-osteoarthritis-pain-model-in-mice
#15
Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Miyako Suzuki, Gen Inoue, Yoshihiro Sakuma, Yasuhiro Oikawa, Sumihisa Orita, Kentaro Uchida, Kazuhisa Takahashi, Masashi Takaso, Seiji Ohtori
BACKGROUND: Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. METHOD: Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints...
November 3, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29100335/breast-cancer-induced-nociceptor-aberrant-growth-and-collateral-sensory-axonal-branching
#16
Matt Austin, Laura Elliott, Niovi Nicolaou, Anna Grabowska, Richard P Hulse
The tumour and neuron interaction has a significant impact upon disease progression and the patients quality of life. In breast cancer patients, it is known that there is an interaction between the tumour microenvironment and the sensory neurons to influence the progression of cancer as well as pain, though these mechanisms still need to be clearly defined. Here it is demonstrated that in a rodent orthotopic model of breast cancer (MDA MB 231) there was an increase in nerve fibre innervation into the tumour microenvironment (protein gene product 9...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093373/-function-of-perivascular-nerves-in-insulin-resistance-induced-hypertension
#17
Shingo Takatori
 Many patients with type 2 diabetes mellitus develop hypertension, although the actual mechanism remains unknown. To clarify possible mechanisms of hypertension development in diabetes, this study investigated the acute or chronic influence of hyperinsulinemia and/or hyperglycemia on the function of perivascular nerves, which play a critical role in vascular tone regulation. Acute hyperinsulinemia in euglycemic pithed rats, which had no autonomic flow, significantly augmented adrenergic nerve-mediated pressor responses and inhibited calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerve-mediated depressor responses...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29089894/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-the-cgrp-binding-monoclonal-antibody-ly2951742-galcanezumab-in-healthy-volunteers
#18
David Monteith, Emily C Collins, Corinne Vandermeulen, Anne Van Hecken, Eyas Raddad, Joel C Scherer, David Grayzel, Thomas J Schuetz, Jan de Hoon
Background: Calcitonin gene-related peptide (CGRP) is pivotal in the pathophysiology of migraine headaches and represents a promising target for migraine treatment. The humanized monoclonal antibody galcanezumab (LY2951742) binds to CGRP and may be effective in migraine prophylaxis. Objectives: The primary objective was to evaluate the safety and tolerability of single and multiple doses of galcanezumab in humans. Secondary objectives included assessing the pharmacokinetics and evaluating target engagement...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29082826/gender-aspects-of-cgrp-in-migraine
#19
Alejandro Labastida-Ramírez, Eloísa Rubio-Beltrán, Carlos M Villalón, Antoinette MaassenVanDenBrink
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...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29080684/chronic-social-stress-ameliorates-psoriasiform-dermatitis-through-upregulation-of-the-hypothalamic-pituitary-adrenal-axis
#20
Oscar Vegas, Brian Poligone, Paul Blackcloud, Elaine S Gilmore, JoAnne VanBuskirk, Christopher T Ritchlin, Alice P Pentland, Scott A Walter, Yasmine Nousari, Francisco Tausk
Acute stress is a physiological response of an organism to adverse conditions, contributing to survival; however, persistence through time may lead to disease. Indeed, exacerbation of inflammatory conditions such as psoriasis has been reported to follow stressors in susceptible patients. Because chronic stress cannot ethically be elicited in patients under controlled laboratory conditions, we studied genetically modified mice that naturally develop psoriasiform dermatitis, and subjected them to an ethological chronic social contact stress paradigm...
October 25, 2017: Brain, Behavior, and Immunity
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