Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity
| Autor: | Sophie Pezet, Anthony H. Dickenson, James Leiper, Claire A. Sand, Stephen B. McMahon, Manasi Nandi, Egle Gaurilcikaite, Richard DʼMello |
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| Přispěvatelé: | Department of Neuroscience, Physiology & Pharmacology, University College of London [London] (UCL), Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Physique pour la médecine (UMR 8063, U1273), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Medicine, Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), PEZET, Sophie, Physique pour la médecine (PhysMed Paris) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Nociception Nervous system Action Potentials Rats Sprague-Dawley Mice chemistry.chemical_compound Nerve Fibers 0302 clinical medicine Ganglia Spinal Cells Cultured ComputingMilieux_MISCELLANEOUS 0303 health sciences Neuronal Plasticity biology Chemistry 3. Good health Nitric oxide synthase NG-Nitroarginine Methyl Ester medicine.anatomical_structure Spinal Cord Neurology [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Dimethylarginine dimethylaminohydrolase inhibition Research Paper Gene isoform Spinal Cord Dorsal Horn medicine.medical_specialty Nerve Tissue Proteins Amidohydrolases Nitric oxide 03 medical and health sciences Asymmetric dimethylargenine Internal medicine medicine Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Nitrites Neuronal nitric oxide synthase 030304 developmental biology Spinal cord Rats Mice Inbred C57BL Disease Models Animal Spinal hyperexcitability Anesthesiology and Pain Medicine Endocrinology Gene Expression Regulation biology.protein Neurology (clinical) Nitric Oxide Synthase Asymmetric dimethylarginine Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | PAIN PAIN, Elsevier, 2015, 156 (10), pp.2052-2060. ⟨10.1097/j.pain.0000000000000269⟩ PAIN, 2015, 156 (10), pp.2052-2060. ⟨10.1097/j.pain.0000000000000269⟩ Pain |
| ISSN: | 0304-3959 1872-6623 |
| Popis: | Supplemental Digital Content is Available in the Text. Inhibition of dimethylarginine dimethylaminohydrolase 1 attenuates pain-related behavior and hyperexcitability in pain conditions associated with excessive nitric oxide production, representing a novel therapeutic target. Activation of neuronal nitric oxide synthase, and consequent production of nitric oxide (NO), contributes to spinal hyperexcitability and enhanced pain sensation. All NOS isoforms are inhibited endogenously by asymmetric dimethylarginine, which itself is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Inhibition of DDAH can indirectly attenuate NO production by elevating asymmetric dimethylarginine concentrations. Here, we show that the DDAH-1 isoform is constitutively active in the nervous system, specifically in the spinal dorsal horn. DDAH-1 was found to be expressed in sensory neurons within both the dorsal root ganglia and spinal dorsal horn; L-291 (NG–[2-Methoxyethyl]-l-arginine methyl ester), a DDAH-1 inhibitor, reduced NO synthesis in cultured dorsal root ganglia neurons. Spinal application of L-291 decreased N-methyl-d-aspartate–dependent postdischarge and windup of dorsal horn sensory neurons—2 measures of spinal hyperexcitability. Finally, spinal application of L-291 reduced both neuronal and behavioral measures of formalin-induced central sensitization. Thus, DDAH-1 may be a potential therapeutic target in neuronal disorders, such as chronic pain, where elevated NO is a contributing factor. |
| Databáze: | OpenAIRE |
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