title: Inflammation of peripheral tissues and injury to peripheral nerves induce differing effects in the expression of the calcium-sensitive N-arachydonoylethanolamine-synthesizing enzyme and related molecules in rat primary sensory neurons.
abstract: Elevation of intracellular Ca2+concentration induces the synthesis of N-arachydonoylethanolamine (anandamide) in a subpopulation of primary sensory neurons. N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is the only known enzyme that synthesizes anandamide in a Ca2+-dependent manner. NAPE-PLD mRNA as well as anandamide's main targets, the excitatory transient receptor potential vanilloid type 1 ion channel (TRPV1), the inhibitory cannabinoid type 1 (CB1) receptor, and the main anandamide-hydrolyzing enzyme fatty acid amide hydrolase (FAAH), are all expressed by subpopulations of nociceptive primary sensory neurons. Thus, NAPE-PLD, TRPV1, the CB1 receptor, and FAAH could form an autocrine signaling system that could shape the activity of a major subpopulation of nociceptive primary sensory neurons, contributing to the development of pain. Although the expression patterns of TRPV1, the CB1 receptor, and FAAH have been comprehensively elucidated, little is known about NAPE-PLD expression in primary sensory neurons under physiological and pathological conditions. This study shows that NAPE-PLD is expressed by about one-third of primary sensory neurons, the overwhelming majority of which also express nociceptive markers as well as the CB1 receptor, TRPV1, and FAAH. Inflammation of peripheral tissues and injury to peripheral nerves induce differing but concerted changes in the expression pattern of NAPE-PLD, the CB1 receptor, TRPV1, and FAAH. Together these data indicate the existence of the anatomical basis for an autocrine signaling system in a major proportion of nociceptive primary sensory neurons and that alterations in that autocrine signaling by peripheral pathologies could contribute to the development of both inflammatory and neuropathic pain.
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.
authors.forename: João
authors.initials: J
authors.lastname: Sousa-Valente
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.|Department of Physiology, University of Debrecen, Medical and Health Science Center, Debrecen, H-4012, Hungary.
authors.forename: Angelika
authors.initials: A
authors.lastname: Varga
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Torres-Perez
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.|Department of Physiology, University of Debrecen, Medical and Health Science Center, Debrecen, H-4012, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jenes
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Wahba
authors.affiliation: Department of Psychological and Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana, 47405.
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.affiliation: The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, 92037.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cravatt
authors.affiliation: Department of Biochemistry, Kagawa University School of Medicine, Miki, Kagawa, 761-0793, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Department of Biochemistry, Kagawa University School of Medicine, Miki, Kagawa, 761-0793, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Physiology, University of Szeged, 6720, Szeged, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Santha
authors.affiliation: Department of Physiology, University of Szeged, 6720, Szeged, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Jancso
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.
authors.forename: Hiren
authors.initials: H
authors.lastname: Tailor
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina do Porto, 4200-450, Porto, Portugal.|I3S Instituto de Investigação e Inovação em Saúde, IBMC Instituto de Biologia Molecular e Celular, 4200-135, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Avelino
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom.
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis; D019771:Axotomy; D015153:Blotting, Western; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000096:biosynthesis; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D059225:Nociception / Q000502:physiology*; D059226:Nociceptive Pain / Q000378:metabolism; D010739:Phospholipase D / Q000096:biosynthesis*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013127:Spinal Nerves / Q000293:injuries*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C527163:Napepld protein, rat; D010739:Phospholipase D; C078814:anandamide
keywords: cannabinoid type 1 receptor; fatty acid amide hydrolase; inflammation; neuropathy; pain; transient receptor potential vanilloid type 1 ion channel