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Gene therapy chronic pain

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https://www.readbyqxmd.com/read/28902127/altered-gene-expression-of-rnf34-and-pacap-possibly-involved-in-mechanism-of-exercise-induced-analgesia-for-neuropathic-pain-in-rats
#1
Shintaro Yamaoka, Yusuke Oshima, Hideki Horiuchi, Tadao Morino, Masayuki Hino, Hiromasa Miura, Tadanori Ogata
Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a candidate for treatment of neuropathic pain, the mechanism underlying its efficacy has not been elucidated. To clarify the molecular mechanism for pain relief induced by exercise, we measured Rnf34 and Pacap mRNA levels in the spinal cord dorsal horn of SNL rats, a model of neuropathic pain...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28868793/chronic-steroid-response-pancytopenia-and-increased-bone-density-due-to-thromboxane-synthase-deficiency
#2
Richa Sharma, Elizabeth Sierra Potchanant, Jennifer E Schwartz, Grzegorz Nalepa
Diagnosis of bone marrow failure (BMF) disorders is challenging but essential for optimal patient management. Here, we report a young adult from nonconsanguineous parents with progressive pancytopenia since childhood, bone pain, increased bone density, and haphazard ossification replacing hematopoiesis within the bone marrow. Sequencing revealed two novel biallelic variants of unknown significance within the thromboxane A synthase gene, TBXAS1 (c.266T > C; c.989T > C), bioinformatically predicted to disrupt the protein...
September 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28854965/adipose-stem-cells-from-chronic-pancreatitis-patients-improve-mouse-and-human-islet-survival-and-function
#3
Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang
BACKGROUND: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation...
August 30, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28822691/fatal-meningitis-in-swine-after-intrathecal-administration-of-adeno-associated-virus-expressing-syngeneic-interleukin-10
#4
Mark D Unger, Josef Pleticha, James E Collins, Anibal G Armien, Jennifer L Brazzell, Laura K Newman, Lukas F Heilmann, Jodi A Scholz, Timothy P Maus, Andreas S Beutler
Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia...
August 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28726577/will-optogenetics-be-used-to-treat-chronic-pain-patients
#5
Hélène Beaudry, Ihab Daou, Alfredo Ribeiro-da-Silva, Philippe Séguéla
Chronic pain affects a third of the population and current treatments produce limited relief and severe side effects. An alternative strategy to decrease pain would be to directly modulate somatosensory pathways using optogenetics. Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits. In preclinical animal models, optical silencing of peripheral nociceptors has been shown to alleviate both inflammatory and neuropathic pain. An opsin-based gene therapy to treat chronic pain patients is not ready yet, but encouraging advances have been made in optical and viral technology...
July 2017: Pain Management
https://www.readbyqxmd.com/read/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#6
Massimo Santoro, Massimiliano Mirabella, Chiara De Fino, Assunta Bianco, Matteo Lucchini, Francesco Losavio, Andrea Sabino, Viviana Nociti
Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28682314/nasal-application-of-hsv-encoding-human-preproenkephalin-blocks-craniofacial-pain-in-a-rat-model-of-traumatic-brain-injury
#7
A C Meidahl, M Klukinov, A Z Tzabazis, J C Sorensen, D C Yeomans
According to Centers for Disease Control and Prevention, each year, an estimated 1.7 million Americans sustain a traumatic brain injury (TBI), which frequently leads to chronic craniofacial pain. In this study we examine a gene therapy approach to the treatment of post-TBI craniofacial neuropathic pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model...
August 2017: Gene Therapy
https://www.readbyqxmd.com/read/28670357/raising-awareness-among-healthcare-providers-about-epidermolysis-bullosa-and-advancing-toward-a-cure
#8
REVIEW
Aaron Tabor, Joseph V Pergolizzi, Guy Marti, John Harmon, Bernard Cohen, Jo Ann Lequang
Objective: Epidermolysis bullosa (EB) is an orphan disease that affects about half a million people worldwide, but may not be familiar to all clinicians. The authors' goal was to present a short description of this condition and current research in the form of a narrative review. Methods: The authors reviewed the literature on epidermolysis bullosa in order to describe the condition and current genetic research. Results: There are at least 31 subtypes of EB, including junctional EB, dystrophic EB, and Kindler syndrome...
May 2017: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28579386/microrna-and-chronic-pain-from-mechanisms-to-therapeutic-potential
#9
REVIEW
María José López-González, Marc Landry, Alexandre Favereaux
Chronic pain is a major public health issue with an incidence of 20-25% worldwide that can take different forms like neuropathic, cancer-related or inflammatory pain. Chronic pain often limits patients in their daily activities leading to despair. Thus, the goal of treatments is to relieve pain sufficiently to enable patients to go back to a normal life. Unfortunately, few patients with chronic pain obtain complete relief from the analgesics that are currently available. It is thus of prime importance to get a better understanding of chronic pain mechanisms to design new therapeutic strategies and pain-killers...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#10
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
July 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28527055/cluster-headache-present-and-future-therapy
#11
Massimo Leone, Alessandro Giustiniani, Alberto Proietti Cecchini
Cluster headache is characterized by severe, unilateral headache attacks of orbital, supraorbital or temporal pain lasting 15-180 min accompanied by ipsilateral lacrimation, rhinorrhea and other cranial autonomic manifestations. Cluster headache attacks need fast-acting abortive agents because the pain peaks very quickly; sumatriptan injection is the gold standard acute treatment. First-line preventative drugs include verapamil and carbolithium. Other drugs demonstrated effective in open trials include topiramate, valproic acid, gabapentin and others...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28480765/targeting-dorsal-root-ganglia-and-primary-sensory-neurons-for-the-treatment-of-chronic-pain
#12
REVIEW
Temugin Berta, Yawar Qadri, Ping-Heng Tan, Ru-Rong Ji
Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons...
July 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28460892/safety-and-efficacy-of-erenumab-for-preventive-treatment-of-chronic-migraine-a-randomised-double-blind-placebo-controlled-phase-2-trial
#13
RANDOMIZED CONTROLLED TRIAL
Stewart Tepper, Messoud Ashina, Uwe Reuter, Jan L Brandes, David Doležil, Stephen Silberstein, Paul Winner, Dean Leonardi, Daniel Mikol, Robert Lenz
BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is important in migraine pathophysiology. We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine. METHODS: This was a phase 2, randomised, double-blind, placebo-controlled, multicentre study of erenumab for adults aged 18-65 years with chronic migraine, enrolled from 69 headache and clinical research centres in North America and Europe...
June 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28440797/potential-mechanisms-of-microrna-141-3p-to-alleviate-chronic-inflammatory-pain-by-downregulation-of-downstream-target-gene-hmgb1-in-vitro-and-in-vivo-studies
#14
W-S Shen, X-Q Xu, N-N Zhai, Z-S Zhou, J Shao, Y-H Yu
The present study aimed to investigate the potential role of microRNA-141-3p (miR-141-3p) in chronic inflammatory pain (CIP) by targeting the high-mobility group box1 (HMGB1) gene. In the in vitro study, BV2 microglial cells were selected and assigned into blank, lipopolysaccharide (LPS), miR-141-3p mimics, mimics control, miR-141-3p inhibitor, inhibitor control, miR-141-3p mimics+LPS, mimics control+ LPS, miR-141-3p inhibitor+LPS and inhibitor control+LPS groups. Ninety-six rats were randomly divided into 8 groups (12 rats in each group): blank control, model control, negative control (NC), miR-141-3p mimics+ complete Freund's adjuvant (CFA), mimics control+CFA, HMGB1 short hairpin RNA (shRNA)+CFA, HMGB1 NC+CFA and miR-141-3p mimics+HMGB1 shRNA+CFA groups...
June 2017: Gene Therapy
https://www.readbyqxmd.com/read/28423456/progesterone-resistance-in-endometriosis-origins-consequences-and-interventions
#15
REVIEW
Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Shu, Robert N Taylor
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis...
June 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28408801/effects-of-%C3%AE-d-mannuronic-acid-as-a-novel-non-steroidal-anti-inflammatory-medication-within-immunosuppressive-properties-on-il17-ror%C3%AE-t-il4-and-gata3-gene-expressions-in-rheumatoid-arthritis-patients
#16
Anis Barati, Ahmad Reza Jamshidi, Hossein Ahmadi, Zahra Aghazadeh, Abbas Mirshafiey
Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28350945/intervertebral-disk-degeneration-and-repair
#17
James Dowdell, Mark Erwin, Theodoe Choma, Alexander Vaccaro, James Iatridis, Samuel K Cho
Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28348938/giardia-filled-pancreatic-mass-in-a-patient-with-recently-treated-t-cell-rich-b-cell-lymphoma
#18
Raj Shah, Talal Asif, Richard Johnson
Giardia lamblia (G. lamblia)-filled pancreatic masses are a rarely reported entity. Furthermore, there are only a few case reports in literature on the association of these masses with cancer. We present a case of a G. lamblia-filled pancreatic cystic mass in a patient with a history of T-cell-rich B-cell lymphoma. The authors performed a PubMed search using (Medical Subject Headings) MeSH terms of pancreas, mass, Giardia, and lymphoma.  A 53-year-old male with past medical and surgical history of T-cell-rich B-cell lymphoma, status post R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) therapy with positron emission tomography (PET) scan showing no residual disease, essential hypertension, and alcohol use disorder presented to the emergency department (ED) with epigastric pain and nausea for one week...
February 9, 2017: Curēus
https://www.readbyqxmd.com/read/28303458/calcitonin-gene-related-peptide-and-pain-a-systematic-review
#19
REVIEW
Wendy Sophie Schou, Sait Ashina, Faisal Mohammad Amin, Peter J Goadsby, Messoud Ashina
BACKGROUND: Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been clarified. METHODS: We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28212278/the-effect-of-the-human-peptide-ghk-on-gene-expression-relevant-to-nervous-system-function-and-cognitive-decline
#20
Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions...
February 15, 2017: Brain Sciences
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