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Calcitonin gene-related peptide

Tal Hoffmann, Katrin Kistner, Richard W Carr, Mohammed A Nassar, Peter W Reeh, Christian Weidner
The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 has previously been associated with inflammatory hyperalgesia. Na1.9 knockout (KO) mice, however, did not seem insensitive in conventional tests of acute nociception. Using electrophysiological, neurochemical, and behavioral techniques, we now show NaV1.9-null mice exhibit impaired mechanical and thermal sensory capacities and reduced electrical excitability of nociceptors. In single-fiber recordings from isolated skin, the electrical threshold of NaV1...
September 15, 2016: Pain
Carl Neuerburg, Theresa Loer, Lena Mittlmeier, Christina Polan, Zsuzsanna Farkas, Lesca Miriam Holdt, Sandra Utzschneider, Jens Schwiesau, Thomas M Grupp, Wolfgang Böcker, Attila Aszodi, Christian Wedemeyer, Christian Kammerlander
Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO...
October 18, 2016: International Journal of Molecular Medicine
Qiang Sun, Tao Zhou, Jun Niu, Peng Wu, Yanan Guo, Yanfei Yang
The aim of this study was to screen the biomarkers of diabetic limb arterial stenosis. Fasting blood samples of 40 patients with diabetic limb arterial stenosis (experimental group), 40 diabetes patients (diabetic control group), and 40 healthy individuals (healthy control group) were collected. Protein-chip assay analysis and ELISA were used to detect tumor necrosis factor α, interleukin-6, endothelin-1, calcitonin gene-related peptide and high-sensitivity C-reactive protein in the three groups. Protein-chip array analysis and ELISA found consistent results that endothelin-1, tumor necrosis factor α, interleukin-6 and high-sensitivity C-reactive protein in the experimental group were significantly up-regulated while the expression of calcitonin gene-related peptide was down-regulated compared with the healthy control group (P < 0...
October 21, 2016: Vascular
Nuray Erin, Tümay İpekçi, Bahar Akkaya, İrem Hicran Özbudak, Mehmet Baykara
Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC...
October 19, 2016: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
Pranav Prasoon, Shivani Gupta, Rahul Kumar, Mayank Gautam, Saroj Kaler, Subrata Basu Ray
OBJECTIVES: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine...
July 2016: Indian Journal of Pharmacology
Xiaodong Li, Mona Hong, Dingliang Zhu, Pingjin Gao
OBJECTIVE: The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. DESIGN AND METHOD: Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II infusion (200 ng/kg/min) in male Sprague-Dawley rats...
September 2016: Journal of Hypertension
Atsushi Minatani, Kentaro Uchida, Gen Inoue, Shotaro Takano, Jun Aikawa, Masayuki Miyagi, Hisako Fujimaki, Dai Iwase, Kenji Onuma, Toshihide Matsumoto, Masashi Takaso
BACKGROUND: Calcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood. METHODS: Synovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3-4) during total knee arthroplasty...
October 17, 2016: Journal of Orthopaedic Surgery and Research
Lauren E Cornelison, Jordan L Hawkins, Paul L Durham
Orofacial pain conditions including temporomandibular joint disorder (TMD) and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons...
October 13, 2016: Neuroscience
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Awa R N'Diaye, Camille Leclerc, Takfarinas Kentache, Julie Hardouin, Cecile Duclairoir Poc, Yoan Konto-Ghiorghi, Sylvie Chevalier, Olivier Lesouhaitier, Marc G J Feuilloley
Staphylococci can sense Substance P (SP) in skin, but this molecule is generally released by nerve terminals along with another neuropeptide, Calcitonin Gene Related Peptide (CGRP). In this study, we investigated the effects of αCGRP on Staphylococci. CGRP induced a strong stimulation of Staphylococcus epidermidis virulence with a low threshold (<10(-12 )M) whereas Staphylococcus aureus was insensitive to CGRP. We observed that CGRP-treated S. epidermidis induced interleukin 8 release by keratinocytes...
October 14, 2016: Scientific Reports
Aichurek Soultanova, Zbigniew Mikulski, Uwe Pfeil, Veronika Grau, Wolfgang Kummer
Members of the calcitonin peptide family-calcitonin gene-related peptide (CGRP), adrenomedullin (AM), and adrenomedullin2/intermedin (IMD)-exert modulatory effects upon monocytes and macrophages of various extrapulmonary origins. Utilizing the rat alveolar macrophage (AMφ) cell line NR8383, we here set out to determine to which extent these three peptides and their receptors are differentially regulated in AMφ and what specific effects they have on AMφ key functions. LPS treatment differentially up-regulated expression of the peptides and receptors...
2016: PloS One
K R Torres-da-Silva, A V Da Silva, N O Barioni, G W L Tessarin, J A De Oliveira, E Ervolino, J A C Horta-Junior, C A Casatti
The spinal cord is involved in local, ascending and descending neural pathways. Few studies analyzed the distribution of neuromediators in the laminae of non-human primates along all segments. The present study described the classic neuromediators in the spinal cord of the non-human primate Sapajus spp. through histochemical and immunohistochemical methods. Nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) method showed neuronal somata in the intermediolateral column (IML), central cervical nucleus (CCN), laminae I, II, III, IV, V, VI, VII, VIII and X, besides dense presence of nerve fibers in laminae II and IX...
September 15, 2016: European Journal of Histochemistry: EJH
Anne-Marie Malfait, Richard J Miller
Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis...
October 12, 2016: Current Osteoporosis Reports
Ali Islek, Aygen Yilmaz, Gulsum Ozlem Elpek, Nuray Erin
AIM: To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. METHODS: Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels...
October 7, 2016: World Journal of Gastroenterology: WJG
De-Li Cao, Bin Qian, Zhi-Jun Zhang, Yong-Jing Gao, Xiao-Bo Wu
Chemokines and their receptors have been demonstrated to be important contributors to the development and maintenance of chronic pain. Recent studies showed that chemokine (C-X-C motif) ligand 1 (CXCL1) and its major receptor CXCR2 are respectively expressed in astrocytes and neurons in the spinal cord and are involved in the maintenance of neuropathic pain and inflammatory pain via astrocytic-neuronal interaction. Here we investigated how CXCL1 and CXCR2 are regulated in the dorsal root ganglion (DRG) after peripheral injection of complete Freund's adjuvant (CFA) and its implication in inflammatory pain...
September 30, 2016: Brain Research Bulletin
Khatera Ibrahimi, Steve Vermeersch, Pascal Frederiks, Vincent Geldhof, Cedric Draulans, Linde Buntinx, Emmanuel Lesaffre, Antoinette MaassenVanDenBrink, Jan de Hoon
BACKGROUND: Migraine is much more common in females than in males, and occurrence is associated with changes in female sex hormones. Calcitonin gene-related peptide (CGRP) plays a key role in migraine, and variations in female sex hormones may affect CGRP sensitivity and/or production. OBJECTIVES: Investigate repeatability, gender differences, influence of the menstrual cycle and of migraine on CGRP-dependent changes in dermal blood flow (DBF). METHODS: CGRP-dependent increases in DBF were assessed using laser Doppler perfusion imaging after topical application of 300 or 1000 µg capsaicin on the forearm of healthy subjects and migraine patients...
September 28, 2016: Cephalalgia: An International Journal of Headache
Lei Sima, Bifa Fan, Longtao Yan, Yuan Shui
Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG). Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9)...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Ruoting Ding, Hui Jiang, Baihui Sun, Xiaoliang Wu, Wei Li, Siyuan Zhu, Congrui Liao, Zhaoming Zhong, Jianting Chen
Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund's adjuvant (CFA) in hindpaw...
September 17, 2016: Redox Biology
Mo-Na Hong, Xiao-Dong Li, Dong-Rui Chen, Cheng-Chao Ruan, Jian-Zhong Xu, Jing Chen, Yong-Jie Wu, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II subcutaneous infusion (200ng/kg/min) in male Sprague-Dawley rats. Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction...
September 21, 2016: Oncotarget
Nick J Spencer, Julian Sorensen, Lee Travis, Lukasz Wiklendt, Marcello C Costa, Timothy James Hibberd
In vertebrates, visceral pain from internal organs is detected by spinal afferents, whose cell bodies lie in dorsal root ganglia (DRG). Until now, all recordings from spinal afferents have been restricted to recording transmission of action potentials along axons, or from cell bodies lying outside their target organ, which is not where sensory transduction occurs. Our aim was to record directly from a major class of spinal afferent within visceral organs, where transduction of sensory stimuli into action potentials takes place...
September 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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