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https://www.readbyqxmd.com/read/28820401/intraepidermal-nerve-fiber-density-in-vulvar-lichen-sclerosus-and-normal-vulvar-tissues
#1
K Milian-Ciesielska, L Chmura, G Dyduch, C Jagers, E Radwanska, D Adamek
Lichen sclerosus (LS) is a chronic and inflammatory disease causing sensory symptoms such as itch and pain and affecting most frequently genital skin of women. Intraepidermal nerve fiber density (IENFD) was examined immunohistologically in 20 vulvar skin biopsies of patients affected by LS and in 20 control vulvar skin biopsies, in order to determine if these sensory sensations originate in changes in the epidermal innervation. Obtained results show fewer protein gene product 9.5 (PGP 9.5) positive intraepidermal nerve fibers (IENF) in LS tissues compared to controls (P = 0...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28817088/the-role-of-neurogenic-inflammation-in-blood-brain-barrier-disruption-and-development-of-cerebral-oedema-following-acute-central-nervous-system-cns-injury
#2
REVIEW
Annabel J Sorby-Adams, Amanda M Marcoionni, Eden R Dempsey, Joshua A Woenig, Renée J Turner
Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke...
August 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28815599/the-reduction-of-intraepidermal-p2x3-nerve-fiber-density-correlates-with-behavioral-hyperalgesia-in-a-rat-model-of-nerve-injury-induced-pain
#3
Malik Bechakra, Barthold N Schüttenhelm, Tiziana Pederzani, Pieter A van Doorn, Chris I de Zeeuw, Joost L M Jongen
Skin biopsies from patients with neuropathic pain often show changes in epidermal innervation, although it remains to be elucidated to what extent such changes can be linked to a particular subgroup of nerve fibers and how these changes are correlated with pain intensity. Here, we investigated to what extent behavioral signs of hyperalgesia are correlated with immunohistochemical changes of peptidergic and non-peptidergic epidermal nerve fibers in a rat model of nerve injury-induced pain. Rats subjected to unilateral partial ligation of the sciatic nerve developed significant mechanical and thermal hyperalgesia as tested by the withdrawal responses of the ipsilateral footpad to von Frey hairs and hotplate stimulation...
August 17, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28792272/trigeminovascular-calcitonin-gene-related-peptide-function-in-cacna1a-r192q-mutated-knock-in-mice
#4
Kayi Y Chan, Alejandro Labastida-Ramírez, Martha B Ramírez-Rosas, Sieneke Labruijere, Ingrid M Garrelds, Alexander Hj Danser, Arn Mjm van den Maagdenberg, Antoinette MaassenVanDenBrink
Familial hemiplegic migraine type 1 (FHM1) is a rare migraine subtype. Whereas transgenic knock-in mice with the human pathogenic FHM1 R192Q missense mutation in the Cacna1a gene reveal overall neuronal hyperexcitability, the effects on the trigeminovascular system and calcitonin gene-related peptide (CGRP) receptor are largely unknown. This gains relevance as blockade of CGRP and its receptor are therapeutic targets under development. Hence, we set out to test these effects in FHM1 mice. We characterized the trigeminovascular system of wild-type and FHM1 mice through: (i) in vivo capsaicin- and CGRP-induced dural vasodilation in a closed-cranial window; (ii) ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis; and (iii) peripheral vascular function in vitro ...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#5
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28762564/capsaicin-induced-rapid-neutrophil-leukocyte-activation-in-the-rat-urinary-bladder-microcirculatory-bed
#6
Péter Járomi, Dénes Garab, Petra Hartmann, Dóra Bodnár, Sándor Nyíri, Péter Sántha, Mihály Boros, Gábor Jancsó, Andrea Szabó
AIMS: This study was initiated to investigate the involvement of neutrophil leukocyte activation in neurogenic inflammation, a process also involved in human urinary pathologies, elicited in the rat urinary bladder by the local administration of capsaicin, the archetypal TRPV1 agonist. The contribution of afferent nerves and sensory neuropeptides to leukocyte activation in the urinary bladder microcirculatory bed was examined. METHODS: Following a 15-min topical application of capsaicin (50 μM), leukocyte-endothelial interactions were examined for an observation period of 45 min with intravital microscopy...
August 1, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28760938/vasorelaxation-to-the-nitroxyl-donor-isopropylamine-nonoate-in-resistance-arteries-does-not-require-perivascular-calcitonin-gene-related-peptide
#7
Alice M H Pinkney, Hamish A L Lemmey, Kim A Dora, Christopher J Garland
Nitroxyl (HNO) donors offer considerable therapeutic potential for the treatment of hypertension-related cardiovascular disorders, particularly heart failure, as they combine an inotropic action with peripheral vasodilation. Angeli's salt is the only HNO donor whose mechanism has been studied in depth, and recently, Angeli's salt vasodilation was suggested to be indirect and caused by calcitonin gene-related peptide (CGRP) released from perivascular nerves after HNO activates TRPA1 (transient receptor potential cation channel subfamily A member 1) channels...
July 31, 2017: Hypertension
https://www.readbyqxmd.com/read/28754314/the-role-of-celsr3-in-the-development-of-central-somatosensory-projections-from-dorsal-root-ganglia
#8
Feifei Wang, Qianghua Wang, Chen Li, Panpan Yu, Yibo Qu, Libing Zhou
Dorsal root ganglion (DRG) neurons receive peripheral somatosensory information and send orderly projections to second-order relay nuclei in the spinal cord and in the brainstem. Atypical cadherin Celsr3 is known to play a critical role in wiring of several central and peripheral axons. Although Celsr3 mRNA is heavily expressed in DRG neurons, its role in the development of somatosensory projections remains unexplored. Here we assessed the role of Celsr3 in DRG using conditional gene inactivation in crosses with Wnt1-Cre mice...
July 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28738112/central-role-of-protein-kinase-a-in-promoting-trigeminal-nociception-in-an-in-vivo-model-of-temporomandibular-disorders
#9
Lindsey K Koop, Jordan L Hawkins, Lauren E Cornelison, Paul L Durham
AIMS: To investigate cellular changes in the spinal trigeminal nucleus (STN) and trigeminal ganglion (TG) associated with trigeminal nociception mediated by inflammation in the temporomandibular joint (TMJ). METHODS: Male Sprague-Dawley rats (n = 86) were utilized to investigate cellular and behavioral responses to prolonged TMJ inflammation caused by bilateral injection of Complete Freund's Adjuvant (CFA) in the TMJ capsules. To investigate the cellular effects of protein kinase A (PKA) in the STN, rats were injected intrathecally with the selective PKA inhibitor KT5720 prior to injection of CFA into both TMJ capsules...
July 2017: Journal of Oral & Facial Pain and Headache
https://www.readbyqxmd.com/read/28736918/phase-1-randomized-double-blind-placebo-controlled-single-dose-and-multiple-dose-studies-of-erenumab-in-healthy-subjects-and-patients-with-migraine
#10
Jan de Hoon, Anne Van Hecken, Corinne Vandermeulen, Lucy Yan, Brian Smith, Jiyun Sunny Chen, Edgar Bautista, Lisa Hamilton, Javier Waksman, Thuy Vu, Gabriel Vargas
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase 1 studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin (Ig)G2 antibodies...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28734832/superficial-esophageal-mucosal-afferent-nerves-may-contribute-to-reflux-hypersensitivity-in-non-erosive-reflux-disease
#11
P Woodland, J L Ooi, F Grassi, K Nikaki, C Lee, J A Evans, N Koukias, C Triantos, S A McDonald, M Peiris, R Aktar, L A Blackshaw, D Sifrim
BACKGROUND & AIMS: Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease (GERD). Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with non-erosive reflux disease (NERD) compared to patients with erosive reflux disease (ERD) or Barrett's esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28731365/chemical-composition-and-antimigraine-activity-of-essential-oil-of-angelicae-dahuricae-radix
#12
Jingbo Sun, He Li, Jinghui Sun, Huimin Liu, Jianguang Chen, Chunmei Wang
The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio...
August 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28726232/-frequent-episodic-migraine-and-calcitonin-gene-related-peptide-influence-of-treatment-with-topiramate-and-zonisamide-on-levels-of-the-peptide
#13
D A Garcia-Estevez, M Pardo-Parrado, S Silvarrey-Rodriguez
INTRODUCTION: The pathophysiology of pain in migraine is related to the activation of the trigeminovascular system by releasing vasoactive neuropeptides, the most important of which is calcitonin gene-related peptide (CGRP), which causes a neurogenic inflammation in the leptomeningeal vessels. AIM: To study whether CGRP is increased in frequent episodic migraine and whether preventive treatment with topiramate or zonisamide modifies its levels. SUBJECTS AND METHODS: We studied 28 patients with episodic migraine with or without aura, in accordance with the International Headache Society criteria, with a frequency of 4-14 days/month...
August 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28720830/effect-of-cxcl12-cxcr4-signaling-on-neuropathic-pain-after-chronic-compression-of-dorsal-root-ganglion
#14
Yang Yu, Xini Huang, Yuwei Di, Lintao Qu, Ni Fan
Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca(2+) response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716587/botulinum-neurotoxin-a-promotes-functional-recovery-after-peripheral-nerve-injury-by-increasing-regeneration-of-myelinated-fibers
#15
Stefano Cobianchi, Jessica Jaramillo, Siro Luvisetto, Flaminia Pavone, Xavier Navarro
The injection of safe doses of botulinum neurotoxin A (BoNT/A) have been reported to be useful for the treatment of neuropathic pain, but it is still unknown how functional recovery is induced after peripheral nerve injury. We evaluated the effects of intranerve application of BoNT/A, on regeneration and sensorimotor functional recovery in partial and complete peripheral nerve injuries in the mouse. After sciatic nerve crush (SNC) and intranerve delivery of BoNT/A (15pg), axonal regeneration was measured by nerve pinch test at different days...
July 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28713051/3d-visualization-and-pathological-characteristics-of-cartilage-and-subchondral-bone-changes-in-the-lumbar-facet-joint-of-an-ovariectomized-mouse-model
#16
Yong Cao, Shuangfei Ni, Tianding Wu, Chunyue Duan, Shenghui Liao, Jianzhong Hu
BACKGROUD CONTEXT: Low back pain (LBP) is more prevalent among postmenopausal women than men. Ovariectomy (OVX) is an established animal model that mimics the estrogen deficiency of postmenopausal women. Little is known about the morphological properties of cartilage and subchondral bone changes in the lumbar facet joint (LFJ) of an OVX mouse model. PURPOSE: The purpose of this study is to characterize the morphological change of cartilage and subchondral bone in LFJ of an OVX mouse model...
July 13, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28707585/migraine-neurogenic-inflammation-drug-development-pharmacochemical-aspects
#17
Melinda Lukács, János Tajti, Ferenc Fülöp, József Toldi, Lars Edvinsson, László Vécsei
BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28706220/opportunities-for-therapeutic-antibodies-directed-at-g-protein-coupled-receptors
#18
REVIEW
Catherine J Hutchings, Markus Koglin, William C Olson, Fiona H Marshall
G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases...
July 14, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28705698/receptor-activity-modifying-protein-dependent-and-independent-activation-mechanisms-in-the-coupling-of-calcitonin-gene-related-peptide-and-adrenomedullin-receptors-to-gs
#19
Michael J Woolley, Christopher A Reynolds, John Simms, Christopher S Walker, Juan Carlos Mobarec, Michael L Garelja, Alex C Conner, David R Poyner, Debbie L Hay
Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, and one of three receptor activity-modifying proteins (RAMPs). How CGRP and AM activate CLR and how this process is modulated by RAMPs is unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP heteromers by measuring the effect of targeted mutagenesis in the CLR transmembrane domain on cAMP production, modeling the active state conformations of CGRP and AM receptors in complex with the Gs C-terminus and conducting molecular dynamics simulations in an explicitly hydrated lipidic bilayer...
July 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#20
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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