Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow
Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions betw...
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Published in | PloS one Vol. 11; no. 9; p. e0161563 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
22.09.2016
Public Library of Science (PLoS) |
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Online Access | Get full text |
ISSN | 1932-6203 1932-6203 |
DOI | 10.1371/journal.pone.0161563 |
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Abstract | Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment. |
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AbstractList | Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment. |
Audience | Academic |
Author | Appel, Lieuwe Långström, Bengt Borsook, David Svärdsudd, Kurt Peterson, Magnus Engler, Henry Catana, Ciprian Sörensen, Jens Fredrikson, Mats Linnman, Clas Furmark, Tomas |
AuthorAffiliation | 3 Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala, Sweden 6 Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden 8 Department of Psychology, Uppsala University, Uppsala, Sweden 7 Neuropsychopharmacology Section, Faculty of Medicine, Imperial College, London, United Kingdom 1 Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States of America 4 Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden 5 Uruguayan Centre of Molecular Imaging (CUDIM), Faculty of Medicine and Faculty of Sciences, University of the Republic, Montevideo, Uruguay 9 Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden Charite Universitatsmedizin Berlin, GERMANY 2 Martinos Center for Biomedical Imaging, Massachusetts General |
AuthorAffiliation_xml | – name: 4 Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden – name: 9 Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden – name: 7 Neuropsychopharmacology Section, Faculty of Medicine, Imperial College, London, United Kingdom – name: 2 Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America – name: 5 Uruguayan Centre of Molecular Imaging (CUDIM), Faculty of Medicine and Faculty of Sciences, University of the Republic, Montevideo, Uruguay – name: 8 Department of Psychology, Uppsala University, Uppsala, Sweden – name: Charite Universitatsmedizin Berlin, GERMANY – name: 1 Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States of America – name: 3 Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala, Sweden – name: 6 Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden |
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Copyright | COPYRIGHT 2016 Public Library of Science 2016 Linnman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2016 Linnman et al 2016 Linnman et al |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: CL KS MP.Performed the experiments: CL KS MP LA HE BL JS MF TF.Analyzed the data: CL MP CC DB MF TF LA BL.Wrote the paper: CL MP MF TF CC DB LA. |
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SubjectTerms | Amygdala Anesthesiology Biology and Life Sciences Brain Brain-derived neurotrophic factor Care and treatment Central nervous system Cerebellum Clinical trials Elbow Elbow (anatomy) Epidemiology Gene expression Hospitals Hostages Inflammation Injuries Medicine Medicine and Health Sciences Mesencephalon Neurokinin NK1 receptors Neurosciences Oncology Pain Pain management Patients Positron emission Positron emission tomography Postcentral gyrus Public health Putamen Research and Analysis Methods Rodents Social Sciences Sports injuries Substance P Tennis Tennis elbow Thalamus Tomography |
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Title | Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow |
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